PubMed Health⌕ Search

Biomedical subjects

M Falkenberg

Publications and source records attributed to M Falkenberg.

At least 37 records · Page 2Linked to original sources
PubMed1997

The UL8 subunit of the heterotrimeric herpes simplex virus type 1 helicase-primase is required for the unwinding of single strand DNA-binding protein (ICP8)-coated DNA substrates.

The Herpes simplex virus type 1 primosome consists of three subunits that are the products of the UL5, UL8, and UL52 genes. The heterotrimeric enzyme has DNA-dependent ATPase, helicase, and primase activities. Earlier studies show that a subassembly consisting of the UL5 and UL52 gene products was indistinguishable from the heterotrimeric enzyme in its helicase and primase activities. We demonstrate here that the UL8 protein is required for the helicase activity of the UL5/52 subassembly on long duplex DNA substrates (>30 nucleotides) with a single-stranded DNA loading site fully coated with the virus-encoded single strand DNA binding protein, ICP8. The Escherichia coli single strand DNA binding protein cannot substitute for ICP8, suggesting a specific physical interaction between ICP8 and the UL8 protein. Surface plasmon resonance measurements demonstrated an interaction between ICP8 and the UL5/52/8 heterotrimer but not with the UL5/52 subassembly or the UL8 protein alone. At a subsaturating level of ICP8, the UL5/52 subassembly does show helicase activity, suggesting that the subassembly can bind to single-stranded DNA but not to ICP8-coated DNA.

Animals↗
PubMed1997

Plasminogen activators and inhibitors in peritoneal tissue.

Serosal trauma elicits an inflammatory response which leads to the deposition of fibrin at injured sites, the residuals of which appear to be essential in excessive tissue repair and formation of intraabdominal adhesions. Local plasminogen activity may modulate this early phase of tissue repair. The present study was undertaken to investigate the distribution and cellular expression of plasminogen activators and their inhibitors in human peritoneal normal and inflamed tissue. Tissue-type plasminogen activator (t-PA) was expressed in subserosal capillary walls, and in normal mesothelium, but not in inflammation. Immunoreactivity for the plasminogen activator inhibitor type 1 (PAI-1) was present in normal mesothelium, and substantially increased in inflammation, where, in addition, immunoreactivity was found throughout the submesothelial tissue. This PAI-1 was partly co-localized with macrophages, as was the urokinase plasminogen activator (u-PA), suggesting an involvement of these cells in peritoneal tissue fibrinolysis. Inflammation or abrasion of the mesothelium during surgery is likely to cause a depletion of the local t-PA source and expose the potentially PAI-1-containing submesothelial tissue, thus promoting persistence of fibrin and formation of adhesions.

Epithelium↗
PubMed1996

Detection of apoptosis in KG-1a leukemic cells treated with investigational drugs.

Four investigational drugs, p-benzoquinone, primine, miconidine acetate, and artesunate (dihydroqinghaosusuccinate), with growth inhibitory activity against flagellatae (e.g. trypanosoma, leptomonas, plasmodium) were investigated for their capability to induce programmed cell death (apoptosis) in human KG-1a leukemic cells. The results were compared with those of three well established cytostatic agents (cisplatin, daunorubicin, cytosine-arabinoside) and ionizing radiation. The antitumor activity of the drugs was validated by a cellular growth inhibition assay. The depletion of glutathione by these four investigational drugs favours the hypothesis that formation of free radicals and subsequent DNA strand breaks may be critical mechanisms of action and that the glutathione redox cycle is involved in detoxification of these reactive molecules.

Antineoplastic Agents↗
PubMed1996

Localization of fibrinolytic activators and inhibitors in normal and atherosclerotic vessels.

UNLABELLED: Local fibrinolytic changes in atherosclerotic arteries have been suggested to influence plaque growth and promote mural thrombosis on ruptured or ulcerated plaques. Increased levels of plasminogen activator inhibitor (PAI-1) have been found in atherosclerotic arteries. In this study tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and PAI-1 were localized in arterial biopsies of healthy and atherosclerotic vessels by immunohistochemistry. The expression of fibrinolytic regulators was related to the distribution of endothelial cells (EC) and macrophages. RESULTS: t-PA was expressed in vasa vasorum. PAI-1 was positive in endothelial cells, in the media and in the adventitia. Increased expression of t-PA, u-PA and PAI-1 was found in atherosclerotic vessels. t-PA, u-PA, PAI-1 and macrophages were co-localized in plaques. These results support the concept that macrophages can be important in the local regulation of fibrinolysis in atherosclerotic vessels.

Adult↗
PubMed1995

The DNA ligands influence the interactions between the herpes simplex virus 1 origin binding protein and the single strand DNA-binding protein, ICP-8.

The herpes simplex virus type 1 (HSV-1) origin binding protein, OBP, is a DNA helicase specifically stimulated by the viral single strand DNA-binding protein, ICP-8. The stimulation is dependent on direct protein-protein interactions between the C-terminal domain of OBP, delta OBP, and ICP 8 (Boehmer, P.E., Craigie, M.C., Stow, N.D., and Lehman, I.R. (1994) J. Biol. Chem. 269, 29329-29334). We have now observed that this interaction is dramatically influenced by the nature of the DNA ligand. Stable complexes between delta OBP, ICP 8, and double-stranded DNA, presented either as a specific duplex oligonucleotide or a restriction fragment containing the HSV-1 origin of replication, oriS, can be detected by gel chromatography and gel electrophoresis. In contrast, a single-stranded oligonucleotide, oligo(dT)65, will completely disrupt the complex between delta OBP and ICP 8. We therefore suggest that the interaction between delta OBP and ICP 8 serves to position the single strand DNA-binding protein with high precision onto single-stranded DNA at a replication fork or at an origin of DNA replication.

Base Sequence↗
PubMed1994

Herpes simplex virus DNA replication: a spacer sequence directs the ATP-dependent formation of a nucleoprotein complex at oriS.

The origin-binding protein (OBP) from herpes simplex virus 1 is a member of the SF2 helicase superfamily and is required for the initiation of DNA synthesis from a viral origin of DNA replication (oriS). The high-affinity binding sites for OBP in oriS, boxes I and II, are separated by an A+T-rich spacer. We used the gel retardation technique to examine the influence of this spacer sequence on the formation of a specific complex, referred to as complex II, between OBP and oriS. The formation of this OBP-oriS complex was greatly promoted by adenosine 5'-[gamma-thio]triphosphate and other nucleotide cofactors. Surprisingly, oriS constructs where the spacer sequence had been altered with approximately half of a helical turn (+4 or -6 base pairs) supported the formation of a more stable complex II than the wild-type origin. DNase I footprinting experiments showed that the cooperative binding of OBP to boxes I and II was affected by the length of the spacer sequence in the same way. In contrast, the ability of oriS-containing plasmids to replicate was most efficient with wild-type oriS. This paradox can be resolved if it is assumed that an ATP-dependent cooperative binding of OBP to properly spaced recognition sequences in oriS is required to induce a conformational change of DNA, thereby facilitating initiation of DNA replication.

Adenosine Triphosphate↗
PubMed1994

Associations with retinopathy in type 2 diabetes: a population-based study in a Swedish rural area.

This population-based study was carried out in a rural area in Sweden. The impact of duration of diabetes, metabolic control, albuminuria, and mode of detection (screening or presence of overt symptoms at the time of diagnosis) on retinopathy in patients with type 2 diabetes aged under 70 years was investigated at a primary health care centre. Ninety-nine percent of all known persons with Type 2 diabetes were under care at the centre. The fundi were examined in all but one of those under 70 years, and a 100% attendance rate was noted with regard to other variables such as albuminuria, glycated haemoglobin, and blood lipids. A team approach (general practitioner, nurse specialist, dietitian, and chiropodist) with patient education as an integral part of the treatment has been practised for the past 15 years. Retinopathy was associated with duration of disease, glycaemic control, systolic blood pressure, detection by overt symptoms, and albuminuria. The risk of retinopathy was not associated with smoking or treatment category. The prevalence of retinopathy was 26.5% in the whole population, and 18.8% among the patients who had been treated for their diabetes at the centre from the time of diagnosis. The importance of an appropriate organization in primary health care for early case finding, near-normal glycaemia, team approach, and structured collaboration with a department of ophthalmology is emphasized in order to realize the aims of the St Vincent declaration to reduce eye complications due to Type 2 diabetes.

Aged↗
PubMed1993

[Foot ulcers in patients with diabetes. Preventive measures reduce the number of amputations].

Reports of preventive management resulting in reduction, by 50 percent or more, of the incidence of major amputation due to foot ulceration in diabetics have now been published from seven different localities, five in Europe (Umeå, Kisa, Lund, London and Geneva) and two in the USA (Tucson and Louisville). The methods used to achieve the reduction are remarkably similar, being based on systematic check-ups for incipient foot ulceration and its putative risk factors. In all three Swedish reports, the work has entailed close liaison with community health centres in the respective areas, which is considered to be of the utmost importance in reaching all diabetics at risk of foot ulcers. Another important prerequisite is a specialised foot clinic for diabetic patients in each area, where the skills of a chiropodist, a physician specialised in diabetes, an orthopaedic surgeon and an orthopaedic shoemaker are available.

Amputation, Surgical↗
PubMed1990

Diabetes care in a rural primary health care district where patient education is given high priority. Metabolic evaluation.

The present population-based study comprises 84% of all known diabetics cared for at a rural primary health care centre. Patient education has been given high priority as an integral part of the treatment provided by a specially trained nurse and dietician under the supervision of the general practitioners. Most of the patients were under good metabolic control, as reflected by HbA1 (diet-treated, n = 119, 7.3 +/- 1.3%; oral agent-treated, n = 127, 7.8% +/- 1.3%; insulin-treated, n = 110, 8.0 +/- 1.3%; reference range 5.3-7.3%). Obvious reasons for any high HbA1 values were found.

Adult↗
PubMed1990

Metabolic control and amputations among diabetics in primary health care--a population-based intensified programme governed by patient education.

The clinical set-up in primary health care, with a specially trained nurse, a dietician, and a chiropodist under the supervision of general practitioners and giving patient education high priority, is evaluated after ten years in practice. Of the 391 patients cared for, 352 had non-insulin-dependent diabetes mellitus, treated as follows; diet 128, oral agents 132, insulin 91. Forty patients had insulin-dependent diabetes mellitus. The metabolic control was good in the great majority of the patients. The mean HbA1C value for the whole diabetic population taken care of at the centre was 5.83% +/- 1.16%, -reference range 3.2-6.0%. The metabolic control is presented according to the European NIDDM Policy Group. On comparing two five-year periods the number of amputations decreased from 18 to 4 (p less than 0.01).

Adult↗