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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 55 records · Page 3Linked to original sources
PubMed1998

Failure of thrombolytic therapy in patients with myocardial infarction is associated with high plasma levels of factor VII antigen.

Thrombolytic therapy in acute myocardial infarction fails to re-establish coronary blood flow in a significant number of patients. One reason for this may be haemostatic imbalance. We investigated whether coagulation factor VII antigen (FVIIag), fibrinogen and protein C were related to reperfusion. Plasma from 45 patients was drawn before treatment and reperfusion assessed by means of continuous, on-line, vector-ECG analysis. Among the 17 patients with no reperfusion, FVIIag levels were significantly higher than among the 28 with signs of reperfusion (560 vs. 410 microg/l median, p = 0.006). Protein C levels where higher in the group with successful reperfusion (1.10 vs. 1.01 U/ml median, p = 0.03), whereas no difference was seen in fibrinogen levels. The findings were not influenced by plasma-triglycerides, body-mass index, age or time between onset of chest pain and thrombolytic therapy. The results suggest that FVII is of importance for the formation as well as resolution of coronary clots.

Adult↗
PubMed1997

Identification and analysis of macrophage-derived foam cells from human atherosclerotic lesions by using a "mock" FL3 channel in flow cytometry.

Macrophages are one of the major cell types in atherosclerotic lesions. They are believed to play an important role in the pathogenesis and development of the lesion, but their functional state and phenotypic characteristics are not well understood. Using flow cytometry, we analyzed surface markers of macrophages extracted from tissue digests. However, conventional techniques were hampered by the abundance of cell debris and extracellular lipids, which co-localized with double-positive cells in all fluorescent plots. We therefore developed a method to overcome this problem by using a novel gating technique in multiparameter flow cytometry. This method utilized the third fluorescence channel (FL3) as a "mock" channel, since no antibody conjugated to an FL3-specific fluorochrome was added to the samples. Cells single-positive for macrophage-specific monoclonal antibodies (mAb) conjugated to phycoerythrin (PE) (FL2) were separated from non-specific fluorescent particles in the FL2 versus FL3 fluorescent plot and a region excluding debris could be set. This was then used as a gate to exclude debris also in the first fluorescence channel (FL1) vs. FL2 plot in which expression of a panel of activation markers identified by fluorescein isothiocyanate (FITC)-conjugated mAb was analyzed. Using this strategy, we were able to identify and analyze the phenotype of macrophages from human atherosclerotic lesions. We were also able to sort these cells and in this way obtained a preparation of macrophage-derived foam cells from the tissue with little contamination of debris.

Antigens, Surface↗
PubMed1997

[Anastomotic leakage after low anterior resection for rectal cancer].

A series of 377 consecutive patients were operated upon with low anterior resection for rectal cancer in the nine Danish departments of surgical gastroenterology during 1992-1993. A retrospective analysis was carried out to calculate the frequency of anastomotic leakage and to evaluate factors of potential influence on the development of leakage according to the literature. Sixty-three patients (17%) developed leakage, which was followed by an increased mortality within the first three postoperative months. Only two variables significantly influenced the leakage rate: male gender was associated with a higher leakage rate (p = 0.02), whereas departments with a low number of rectal cancer surgeons had a low rate of anastomotic leakage (p = 0.02). In conclusion, the rather high frequency of anastomotic leakage calls for further clinical and pathogenetic research in this field. Until then, we recommend the routine use of a peroperative leakage test and selective use of prophylactic ostomy in cases of unsatisfactory anastomosis. Furthermore, it is recommended that low anterior resection for rectal cancer is limited to few surgeons in each department in order to ensure a uniform quality and hopefully also thereby reduce the rate of anastomotic leakage.

Adenocarcinoma↗
PubMed1997

Folate receptors in malignant and benign tissues of human female genital tract.

We have characterized the folate receptor in malignant and benign tissues of human female genital tract (Fallopian tube and benign and malignant tissues of uterus). Radioligand binding displayed characteristics similar to those of other folate binding proteins. Those include a high-affinity type of binding (K = 10(10)M-1), apparent positive cooperativity, a slow dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition of binding by folate analogues. The gel filtration profile of Triton X-100 solubilized tissue contained two large peaks of 3H-folate labelled protein (> = 130 and 100 kDa) as well as a 25 kDa peak. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The large molecular size forms on gel filtration appear to represent folate receptors having a hydrophobic membrane anchor inserted into Triton X-100 micelles. The folate receptor of female genital tract showed cross-reactivity in ELISA and positive immunostaining with rabbit antibodies against human milk folate binding protein. Variations in the ratio of immunoresponse to total high affinity folic acid binding suggests the presence of multiple isoforms of the receptor in different types of malignant and benign tissues.

Adenocarcinoma↗
PubMed1997

A common thrombomodulin amino acid dimorphism is associated with myocardial infarction.

Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.

Adult↗
PubMed1996

Characterization of the folate receptor in human molar placenta.

We have characterized a high-affinity folate receptor in human molar placenta tissue. Radioligand binding exhibited characteristics typical of other high-affinity folate binding proteins. Those included, positive cooperativity, a tendency to increased binding affinity with decreasing receptor concentration, a slow ligand dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition by folate analogues. The folate receptor cross-reacted with antibodies against human milk folate binding protein, e.g. the syncytothrophoblastic layer of molar placenta tissue sections showed strongly positive immunostaining. The gel filtration profile contained two radioligand-bound peaks (25 and 100 kDa), however, with considerable overlap. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The folate receptor in placental tissue may play a crucial role in the transfer of folate from maternal circulation to the fetus.

Antidotes↗
PubMed1996

Erectile dysfunction in men with chronic medical illness.

This study examined interrelationships of psychosocial variables found in a psychological evaluation for erectile disorder in 75 male veterans with chronic medical illness. Patients whose partners participated in the evaluation were compared with those whose partners were not involved, and agreement on measures between patients and partners was examined. Finally, a principal components analysis was performed to assess the primary dimensions underlying the variance in mental health and sexual functioning variables. Five factors were identified, accounting for 65.5% of the variance. Results of these analyses are discussed in order to obtain an understanding of the interrelationship between behavioral, psychological, and interpersonal variables in the onset and course of sexual dysfunction.

Adult↗
PubMed1996

Retinol-binding protein and transferrin in urine. New markers of renal function in essential hypertension and white coat hypertension?

We studied the 24 h urinary excretion of albumin, transferrin, immunoglobulin G, and retinol-binding protein in individuals with essential hypertension, white coat hypertension, and normotension. In 56 individuals, we measured the 24 h ambulatory blood pressure (AMBP). The individuals could be divided into three groups: 26 hypertensives, 14 white coat hypertensives, and 16 normotensives. Daytime AMBP values were (median values with range in parentheses, mm Hg): hypertensives 158/105 (198 to 121/95 to 120), white coat hypertensives 141/83 (161 to 129/72 to 90), and normotensives 123/75 (148 to 102/63 to 86). We determined with immunochemical methods the 24 h urinary excretions of albumin, transferrin, and immunoglobulin G, all markers of glomerular dysfunction, and retinol-binding protein, a marker of impaired proximal tubular function. We found a significantly higher excretion of albumin and transferrin in hypertensives (P < .0000/P < .0001) and in white coat hypertensives (P < .003/P < .02) compared to normotensives. Out of 26 hypertensives, seven had microalbuminuria (> or = 30 to < 300 mg albumin/ 24 h). Two cases of microalbuminuria were found among the 14 white coat hypertensives. Immunoglobulin G excretion was not significantly increased in any of the hypertensive groups. Retinol-binding protein excretion was significantly higher in hypertensive patients (P < .007), whereas no elevation was observed in persons with white coat hypertension. In hypertensives, a significant correlation was found between urinary excretion of albumin and transferrin and office blood pressure and systolic AMBP. There was no significant correlation between the urinary excretions of IgG and retinol-binding protein and blood pressures in any of the three groups. Our findings indicate that patients with white coat hypertension, like hypertensives, have a selective type of glomerular dysfunction. However, proximal tubular dysfunction was seen only in hypertensives. Urinary excretions of albumin, transferrin, and retinol-binding protein may be useful as markers of glomerular and tubular dysfunction in essential hypertension.

Biomarkers↗
PubMed1996

Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries.

OBJECTIVE: Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q506). To test the importance of the FV:Q506 mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years. DESIGN, SETTING AND SUBJECTS: In a retrospective case-control study, the FV:Q506 mutation was investigated in 101 survivors of MI (79 men, 22 women) and in 101 healthy sex- and age-matched controls. MAIN OUTCOME MEASURE: The prevalence of FV:Q506 mutation. RESULTS: The FV:Q506 mutation was found in 18% of patients versus 11% of controls (P = 0.16). The mutation was significantly more frequent amongst male patients than amongst controls (23 vs. 10%; P = 0.03), the calculated odds ratio being 2.6 (95% CI, 1.1-6.4). CONCLUSION: The high prevalence of the FV:Q506 mutation found amongst Swedish MI patients, especially amongst men, is noteworthy, and calls for further studies on the outcome of MI in APC-resistant patients. The prevalence of the FV:Q506 mutation in controls is higher than figures reported from other countries, suggesting that at least 10% of the Swedish population are carriers of a congenital prothrombotic disorder.

Adult↗
PubMed1996

Structural features of a close homologue of L1 (CHL1) in the mouse: a new member of the L1 family of neural recognition molecules.

We have identified a close homologue of L1 (CHL1) in the mouse. CHL1 comprises an N-terminal signal sequence, six immunoglobulin (Ig)-like domains, 4.5 fibronectin type III (FN)-like repeats, a transmembrane domain and a C-terminal, most likely intracellular domain of approximately 100 amino acids. CHL1 is most similar in its extracellular domain to chicken Ng-CAM (approximately 40% amino acid identity), followed by mouse L1, chicken neurofascin, chicken Nr-CAM, Drosophila neuroglian and zebrafish L1.1 (37-28% amino acid identity), and mouse F3, rat TAG-1 and rat BIG-1 (approximately 27% amino acid identity). The similarity with other members of the Ig superfamily [e.g. neural cell adhesion molecule (N-CAM), DCC, HLAR, rse] is 16-11%. The intracellular domain is most similar to mouse and chicken Nr-CAM, mouse and rat neurofascin (approximately 60% amino acid identity) followed by chicken neurofascin and Ng-CAM, Drosophila neuroglian and zebrafish L1.1 and L1.2 (approximately 40% amino acid identity). Besides the high overall homology and conserved modular structure among previously recognized members of the L1 family (mouse/human L1/rat NILE; chicken Ng-CAM; chicken/mouse Nr-CAM; Drosophila neuroglian; zebrafish L1.1 and L1.2; chicken/mouse neurofascin/rat ankyrin-binding glycoprotein), criteria characteristic of L1 were identified with regard to the number of amino acids between positions of conserved amino acid residues defining distances within and between two adjacent Ig-like domains and FN-like repeats. These show a collinearity in the six Ig-like domains and four adjacent FN-like repeats that is remarkably conserved between L1 and molecules containing these modules (designated the L1 family cassette), including the GPI-linked forms of the F3 subgroup (mouse F3/chicken F11/human CNTN1; rat BIG-1/mouse PANG; rat TAG-1/mouse TAX-1/chicken axonin-1). The colorectal cancer molecule (DCC), previously introduced as an N-CAM-like molecule, conforms to the L1 family cassette. Other structural features of CHL 1 shared between members of the L1 family are a high degree of N-glycosidically linked carbohydrates (approximately 20% of its molecular mass), which include the HNK-1 carbohydrate structure, and a pattern of protein fragments comprising a major 185 kDa band and smaller fragments of 165 and 125 kDa. As for the other L1 family members, predominant expression of CHL1 is observed in the nervous system and at later developmental stages. In the central nervous system CHL1 is expressed by neurons, but, in contrast to L1, also by glial cells. Our findings suggest a common ancestral L1-like molecule which evolved via gene duplication to generate a diversity of structurally and functionally distinct yet similar molecules.

Animals↗
PubMed1996

Effects of masticatory muscle function on bone mass in the mandible of the growing rat.

The effect of altered masticatory muscle function on bone mass at different sites in the rat mandible was studied using aluminium as a reference substance in computer-assisted image analysis. Forty-two growing male rats were divided into three groups, of which one group was killed at the beginning of the experiment to provide baseline values. Of the remaining two, one received a hard diet (control group) and the other a soft diet. After 28 days the rats were killed and the mandibles were excised. Lateral radiographs were taken of the mandible halves together with an aluminium stepwedge and then analysed by an image analysis system. Radiographic bone mass was measured in the transverse plane as "aluminium-equivalent thickness' in millimetres. Standardized areas were chosen to investigate regions with different functional demands. Significant differences were found between the groups in the alveolar bone of the molars and the incisor, as well as in the condylar costa and the condylar process. Significant differences were also found in some areas related to muscle insertion, such as the anterior lower border of the ramus, whereas no statistically significant differences could be found in others, such as the posterior lower border of the angular process. In conclusion, altered masticatory function influences the amount of bone mass in certain parts of mandible, where changes in applied bending forces have possibly altered the bone strain.

Animals↗
PubMed1996

Phosphorus-31 MR spectroscopy in the preoperative evaluation of symptomatic unilateral carotid artery stenosis.

PURPOSE: The purpose of this study was to examine the potential of 31P-MRS (MR spectroscopy) in the pre- and postoperative evaluation of patients referred for endarterectomy. MATERIAL AND METHODS: Nine patients with unilateral, hemodynamically significant stenosis in the region of the common carotid bifurcation were examined pre- and post-operatively with CT, SPECT (regional cerebral blood flow), transcranial Doppler, and duplex sonography, and they also underwent neuropsychologic investigation. Phosphorus-31 MRS of each hemisphere was performed before and 27-148 days after surgery. The relative concentrations of phosphomono- and -diesters, inorganic phosphate, phosphocreatine, and ATP were estimated. RESULTS: No definite changes in concentrations could be detected for any of the metabolites. CONCLUSION: The lack of changes was probably due to well-functioning collaterals and to the partial volume effect, whereby changes in a focal region are hidden when larger volumes are studied.

Aged↗
PubMed1996

Effect of milk processing on the concentration of folate-binding protein (FBP), folate-binding capacity and retention of 5-methyltetrahydrofolate.

The main objective of this study was to investigate the effects of pasteurisation, UHT processing and fermentation on the concentration of folate-binding proteins (FBP) and their folate binding capacity in comparison with the retention of the most predominant folate from, 5-CH3THF. The amount of folate-binding protein (FBP) was analysed using enzyme-linked immunosorbent assay (ELISA). Unprocessed milk and pasteurised milk were found to contain similar amounts, 211 and 168 nmol/l, of FBP, respectively. UHT-processed milk and Yoghurt naturelle, both processed at temperatures above 90 degrees C, contained only 5.2 and 0.2 nmol/l FBP, respectively. As an indication of the protein-binding capacity free and protein-bound folates were analysed after charcoal treatment using the radio-protein binding assay method (RPBA). These results indicated that all folates in unprocessed milk and pasteurised milk were protein-bound, while folates in UHT-processed milk and Yoghurt naturelle occurred freely which is supported by our findings on FBP. High-performance liquid chromatography analysis indicated that unprocessed milk, pasteurised milk, UHT-processed milk and Yoghurt naturelle contained 44.8 +/- 2.1 (n = 10), 41.1 +/- 0.9 (n = 10), 36.1 +/- 1.8 (n = 10) and 35.6 +/- 9.1 micrograms/l (n = 10) 5-methyltetrahydrofolates (5-CH3THF), respectively, after deconjugation. Corresponding values for total milk folates analysed using radio-protein binding assay were 80.4 +/- 0.9 (n = 10), 64.2 +/- 2.7 (n = 10), 48.2 +/- 1.8 (n = 10) and 54.0 +/- 8.2 micrograms/l (n = 10), respectively. Hence, both methods indicated significant (P < 0.05) losses of 5-CH3THF as a result of pasteurisation, UHT processing and fermentation, compared with unprocessed milk. In spite of apparent discrepancies in folate concentrations obtained using the two different methods, these results support the equimolar ratio of FBP and folates in unprocessed and pasteurised milk when data on 5-CH3THF, obtained using HPLC were corrected for differences in recovery. Thus, heat processing of milk not only reduced the amount of 5-CH3 THF significantly, but also changed the concentration of FBP and the folate-binding capacity of FBP, which may have implications on the bioavailability of milk folates.

Animals↗
PubMed1996

Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency.

Inherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gln (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2), which is a marker of hypercoagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gln mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1 + 2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 +/- 0.7 nM; mean +/- SD) and in 48 protein S deficient cases (1.9 +/- 0.9 nm), than in 100 unaffected relatives (1.3 +/- 0.5 nM). Warfarin therapy decreased the F1 + 2 levels, even in those four patients who had combined defects (0.5 +/- 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

Adolescent↗