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Biomedical subjects

J Ingerslev

Publications and source records attributed to J Ingerslev.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1990

Pregnancy zone protein: a re-evaluation of serum levels in healthy women and in women suffering from breast cancer or trophoblastic disease.

Pregnancy zone protein (PZP) and alpha 2-macroglobulin (alpha 2M) serum concentrations were studied in healthy female donors, in women suffering from benign and malignant breast tumours, and in relation to normal and abnormal pregnancies. PZP was found to be useless as a tumour marker. Thus, PZP levels in breast cancer patients did not differ from those of fibroadenoma patients or healthy women. There was no correlation between PZP (or alpha 2M) concentrations and the pTNM-classification or metastatic burden of the breast cancer patients. Moreover, PZP levels were unaffected by cancer treatment and the course of disease. Neither patients nor control donors showed any age-dependent increase in circulating PZP and the mean serum value (8.38 +/- 4.83 mg/l, mean +/- SD) determined in a population of 154 non-pregnant women was considerably lower than that of most previous reports. Serum concentrations were unchanged during the normal menstrual cycle, but increased during pregnancy. However, late pregnancy sera (35th gestational week) contained significantly less PZP than previously reported by others, and non-pregnancy levels were observed in one out of 22 cases. Results obtained in hydatidiform mole patients were similar to findings in normal pregnancy. Neither serum 17 beta-oestradiol nor morphological differentiation between complete and partial mole showed any correlation with circulting PZP levels. Apart from a moderate increase during gestation, alpha 2M concentrations showed little variation between the populations examined.

Adult↗
PubMed1990

Serum ferritin and iron status in a population of 'healthy' 85-year-old individuals.

Iron status, including S-ferritin, S-iron, S-total iron binding capacity (TIBC), TIBC saturation, haemoglobin (Hb) and dietary iron intake, was assessed in a population study comprising 92 healthy 85-year-old subjects (32 males, 60 females). S-iron, S-TIBC, TIBC saturation and S-ferritin values were not significantly different in the two sexes. Males had a geometric mean S-ferritin of 130 micrograms/l, females of 98 micrograms/l. Ferritin levels less than 15 micrograms/l (i.e. depleted iron stores) were found in one female (1.6%); and in one male (3.1%), who in addition had iron deficiency anaemia. None of the females displayed latent iron deficiency (i.e. S-ferritin less than 15 micrograms/l and S-TIBC saturation less than 15%) or iron deficiency anaemia. Arithmetic mean Hb was 145 +/- 13 (SD) g/l (9.0 +/- 0.8 mmol/l) in males and 139 +/- 11 g/l (8.6 +/- 0.7 mmol/l) in females (p less than 0.02). Median nutritional iron intake was 10 mg/day (range 3-17), higher in males (median 12) than in females (median 9) (p less than 0.0001). Iron intake showed significant correlations to S-iron, S-TIBC and TIBC saturation, but not to S-ferritin.

Aged↗
PubMed1990

Haemostatic measures in type 2 diabetic patients with microalbuminuria.

The major cause of disability and early mortality in Type 2 diabetes is cardiovascular disease. An enhanced urinary albumin excretion is strongly predictive of increased mortality, but the causal relationship behind this association is unclear. Abnormalities in the haemostatic system may be involved in the vascular pathology. We therefore studied the level of von Willebrand factor (vWf:Ag), factor VIII (VIII:Ag), fibrinogen, and fibronectin in male diabetic patients 50-70 years of age, with normal albumin excretion (n = 14), microalbuminuria (n = 14), and frank albuminuria (n = 7). Fourteen healthy age-matched males served as a reference group. There were no significant differences between normo- and micro-albuminuric patients but vWf:Ag (p less than 0.01), VIII:Ag (p less than 0.01), and fibrinogen (p less than 0.05) were increased in those with frank albuminuria. Urinary albumin excretion rate was significantly correlated to vWf:Ag (r = 0.46, p = 0.005), VIII:Ag (r = 0.45, p = 0.007), and fibrinogen (r = 0.49, p = 0.003). The known duration of diabetes was correlated to vWf and F VIII. The increased level of vWf:Ag in Type 2 diabetes and the significant association to the urinary albumin excretion rate may suggest a linkage between albuminuria and cardiovascular disease. However, the present study demonstrated no increase in haemostatic variables in patients with microalbuminuria as compared with those with normal albumin excretion.

Aged↗
PubMed1990

Growth hormone (GH) therapy in GH-deficient patients, the plasma factor VIII-von Willebrand factor complex, and capillary fragility. A double-blind, placebo-controlled crossover study.

It has been suggested that growth hormone (GH) plays a role in the regulation of Factor VIII-von Willebrand factor complex and other parameters associated with haemostasis and vascular integrity. However, limited information is available on these features in GH-deficient patients. We therefore examined, in a double-blind, placebo-controlled crossover design, the effects of 4 months' replacement therapy with biosynthetic human GH in 22 GH-deficient adults on circulating haemostatic parameters and capillary fragility. A non-significant increase in the plasma levels of von Willebrand factor antigen (p = 0.09), Factor VIII antigen (p = 0.6), fibrinogen (p = 0.4) and fibronectin (p = 0.2) was observed at the end of the GH treatment period along with a non-significant decrease in tissue-type plasminogen activator (p = 0.2). Capillary fragility tended to decrease during GH therapy (p = 0.2). All variables remained within the reference range following both the placebo and the GH treatment period. It is concluded that GH-deficient patients display normal levels of the haemostasis parameters recorded, and that 4 months of GH therapy in a conventional replacement dose does not significantly affect these values.

Adolescent↗
PubMed1990

Total knee arthroplasty in classic hemophilia.

Thirteen semiconstrained total knee arthroplasties (TKA) were performed in nine men with classic hemophilia. The average age at surgery was 38 years, the average Factor VIII administration during hospitalization was 84.222 units, and the average hospitalization time was 33 days. Four patients (44%) died during the observation period, three from acquired immunodeficiency syndrome (AIDS) contracted through contaminated Factor VIII plasma concentrates and one from sudden cardiac arrest. One of the patients who died from AIDS had a positive test for human immunodeficiency virus (HIV) at surgery. He died three months after the arthroplasty. The remaining two patients contracted AIDS one year and four years after the arthroplasty. All but one patient were followed for at least one year, with an average follow-up period of 43 months. Using The Hospital for Special Surgery Knee Rating Scale, the overall result was excellent in nine knees and good in three knees. All patients were completely relieved of pain. TKA in hemophiliacs is an effective treatment for otherwise intractable chronic knee pain due to severe joint degeneration. However, caution should be taken in HIV-positive patients owing to the challenge of the patient's immune system and the risk of transmitting the virus to the hospital staff.

Acquired Immunodeficiency Syndrome↗