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Biomedical subjects

M S Hansen

Publications and source records attributed to M S Hansen.

At least 19 recordsLinked to original sources
PubMed1997

Human immunodeficiency virus type 2 preintegration complexes: activities in vitro and response to inhibitors.

We have established an assay for the function of preintegration complexes (PICs) of human immunodeficiency virus type 2 (HIV-2) to investigate the integration mechanism and to develop additional methods for screening candidate integration inhibitors. We partially purified HIV-2 PICs and found that they were competent to integrate viral cDNA into target DNA in vitro. Analysis of the structure of integration products on Southern blots revealed forms consistent with those expected for authentic integration products and circular forms containing one and two long terminal repeats. To determine whether in vitro products had the detailed structure expected of integration products formed in vivo, we recovered product molecules and analyzed junctions between viral DNA and target DNA. In the integration junctions of all nine molecules examined, we observed the 5-bp duplication of target sequence characteristic of integration in vivo. We investigated the possible role in integration of Vpx, a protein present in HIV-2 but not HIV-1 and known to be present in viral cores. Although association of Vpx with viral cDNA was detectable, our studies revealed no obvious role of Vpx in integration since the activities of PICs from Vpx- virions were indistinguishable from those of wild type. We have also investigated the use of HIV-2 PICs as tools to screen candidate HIV inhibitors. Assays with HIV-2 PICs, like assays with HIV-1 PICs, were less sensitive to many small molecule inhibitors than were reactions with purified integrase only. Comparing results of assays with PICs from HIV-1 and HIV-2 may be particularly useful, since inhibitors active against both may be more widely useful and less vulnerable to escape mutants.

Anti-HIV Agents↗
PubMed1996

Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age subgroups of schizophrenic patients.

1. The purpose of this retrospective chart review study was to determine whether broad and stringent criteria differentially impact clozapine eligibility in ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients charts were selected from a random cluster sample of mental health patients known to the city and county of San Francisco. Information related to clozapine eligibility was abstracted by trained non-clinical personnel. The impact of subgroup membership on eligibility was examined using logistic regression procedures. 3. Even under the broadest interpretation of FDA requirements for clozapine use, Asian patients were less likely to be eligible, since fewer Asian patients met clozapine treatment requirements. Under more stringent eligibility criteria, older patients were more likely to be excluded from eligibility when TD does not automatically satisfy treatment criteria, and younger patients were more likely to lose eligibility if the number of required adequate medication trials increases to three. 4. Broad eligibility criteria tend to differentially exclude Asian patients while more stringent criteria differentially exclude younger and older patients.

Adolescent↗
PubMed1995

Unexpected hepatotoxicity after priming and treatment with molgramostim (rhGM-CSF) in acute myeloid leukemia during induction chemotherapy.

The effect of supplementing induction chemotherapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied in a randomized trial of 18 patients with acute myeloid leukemia (AML). Ten patients received rhGM-CSF, starting on day one to three before chemotherapy and continued for a maximum of 21 days after the start of induction treatment. Unexpected adverse effects of rhGM-CSF and chemotherapy combination included a transient decline in plasma coagulation factors II, VII, and X (5 of 5 patients) and an increased transcapillary escape rate of albumin (in 3 of 3 patients tested). The decline in coagulation factors was prevented in subsequent patients by prophylactic treatment with vitamin K. Although the small number of patients studied may not allow a definite conclusion, caution with regard to liver function should be shown in combining rhGM-CSF with intensive chemotherapy.

Adult↗
PubMed1995

Structural interactions between retroviral Gag proteins examined by cysteine cross-linking.

We have examined structural interactions between Gag proteins within Moloney murine leukemia virus (M-MuLV) particles by making use of the cysteine-specific cross-linking agents iodine and bis-maleimido hexane. Virion-associated wild-type M-MuLV Pr65Gag proteins in immature particles were intermolecularly cross-linked at cysteines to form Pr65Gag oligomers, from dimers to pentamers or hexamers. Following a systematic approach of cysteine-to-serine mutagenesis, we have shown that cross-linking of Pr65Gag occurred at cysteines of the nucleocapsid (NC) Cys-His motif, suggesting that the Cys-His motifs within virus particles are packed in close proximity. The M-MuLV Pr65Gag protein did not cross-link to the human immunodeficiency virus Pr55Gag protein when the two molecules were coexpressed, indicating either that they did not coassemble or that heterologous Gag proteins were not in close enough proximity to be cross-linked. Using an assembly-competent, protease-minus, cysteine-minus Pr65Gag protein as a template, novel cysteine residues were generated in the M-MuLV capsid domain major homology region (MHR). Cross-linking of proteins containing MHR cysteines showed above-background levels of Gag-Gag dimers but also identified a novel cellular factor, present in virions, that cross-linked to MHR residues. Although the NC cysteine mutation was compatible with M-MuLV particle assembly, deletions of the NC domain were not tolerated. These results suggest that the Cys-His motif is held in close proximity within immature M-MuLV particles by interactions between CA domains and/or non-Cys-His motif domains of the NC.

3T3 Cells↗
PubMed1995

Effects of stringent criteria on eligibility for clozapine among public mental health clients.

OBJECTIVE: This study estimated rates of eligibility for treatment with clozapine among clients in a public mental health system using criteria with various degrees of restrictiveness. METHODS: A stratified, random cluster sample of 293 clients was selected from among all clients with schizophrenic disorders known to the mental health system of the city and county of San Francisco during 1991. Data on variables associated with eligibility for clozapine were abstracted from clinical records, and eligibility was estimated using broad and stringent criteria. RESULTS: An estimated 42.9 percent of the clients were eligible for clozapine using broad eligibility criteria that included a diagnosis of schizophrenia or schizoaffective disorder, two previous neuroleptic trials of at least 600 mg per day chlorpromazine equivalents for at least four weeks or tardive dyskinesia, Global Assessment of Functioning score less than 61, and no contraindications. Eliminating eligibility due to tardive dyskinesia alone, excluding persons with schizoaffective disorder, requiring six-week medication trials, and requiring three adequate medication trials instead of two resulted in substantial reductions in the rate of eligibility. CONCLUSIONS: Varying interpretations of the criteria for clozapine treatment listed in the medication package insert dramatically affect patients' eligibility for clozapine. Mental health agencies should endeavor to maintain a balance between restricting use of clozapine due to cost and providing it to the full spectrum of patients who might benefit from the medication.

Adolescent↗
PubMed1994

Prevalence of fra(X) in the county of Funen in Denmark is lower than expected.

Population based cytogenetic fra(X) surveys have not previously been reported from Denmark. In the present study we present an estimate of fra(X) based on 1) information from the Danish Central Cytogenetic Registry of diagnosed fra(X) males of all age groups in all Denmark in the period 1980-1992 and 2) a systematic cytogenetic fra(X) survey of 175 of 8-10-year-old children with special educational needs resident in a defined, demographically representative area of Denmark (the county of Funen). The study was performed in 1988-90 before the cloning of the FMR-1 gene. In the county of Funen there were 7,837 male children in the age group of 8-10 years. In the cytogenetic survey of learning disabled children, no fra(X) positive was diagnosed. There were 99 registered males with fra(X) in all Denmark, equivalent to a prevalence of 0.04 per 1,000 males (confidence interval 0.032:1,000-0.048:1,000). Molecular fra(X) surveys of different, large populations are needed in order to estimate the frequency of fra(X) and clarify whether significant differences in prevalence exist in different populations.

Child↗
PubMed1993

In vivo demonstration of focal fibrinolytic activity in abdominal aortic aneurysms.

Disseminated intravascular coagulation in association with arterial aneurysm has been reported in several cases. Reports have suggested a continuous deposition of fibrin and/or platelets at the site of the aneurysm followed by fibrinolysis as responsible for this disorder. To further investigate this theory we studied the in vivo binding of an indium-111-labelled monoclonal antibody against human tissue plasminogen activator (t-PA), a proteolytic enzyme involved in the fibrinolysis. Six patients admitted to the hospital for elective resection of an abdominal aortic aneurysm with a mural thrombus were examined. One day before the operation the antibody was injected intravenously. Scintigrams acquired just prior to operation and tissue samples obtained at the operation revealed an increased t-PA accumulation in the wall of the aneurysm. The study demonstrates in vivo, focally increased fibrinolytic activity in the aneurysm, explaining the coagulopathy observed in these patients.

Aged↗
PubMed1992

[Quality assurance of results of clinical chemical analyses in Danish hospital laboratories].

During the past 35 years, voluntary professional assessment of quality of the results of analyses in Danish hospital laboratories has been undertaken under the auspices of the Danish Society of Clinical Chemistry. The analytical quality of the laboratories is described by their "imprecision" and "accuracy" as expressed by "coefficient of variation" and "bias", respectively. The participation in these programmes was 90%. During the period between 1968 and 1987, inter-laboratory variation decreased markedly where all analyses were concerned. To ensure the necessary and adequate quality, establishment of specifications of quality based on clinical/biological goals of quality has proved necessary. The commonest reasons for large imprecision and bias from the target values are less specific methods of analysis, errors in calibration and sporadic "outliers". As the result of a stable organisation for ensuring quality, Denmark is well equipped for the introduction of the great demands in documentation of quality which may be anticipated from the Common Market during the immediate future.

Chemistry Techniques, Analytical↗
PubMed1992

Abuse of monoamine oxidase inhibitors.

Monoamine oxidase inhibitors, like other antidepressants, generally are considered free of risk for abuse. There is, however, some evidence that MAOIs possess dependence and abuse potential for some patients. We will review the available literature and describe three current cases. Recommendations for treatment are discussed briefly.

Adult↗
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↗
PubMed1984

Fibronectin and coagulation factor XIII increases blood platelet adhesion to fibrin.

Fibronectin is covalently linked to fibrin during clot formation by coagulation factor XIII and has been suggested as a possible mediator of platelet adhesion to collagen. Fixed human platelets were found to adhere to fibrin. This adhesion was significantly increased when fibronectin was incorporated into the fibrin network, and was supported by factor XIII.

Factor XIII↗
PubMed1984

An abnormal fibrinogen (Copenhagen II) with increased sialic acid content associated with thrombotic tendency and normal liver function.

An increased sialic acid content of the fibrinogen molecule is found in foetal fibrinogen and as an acquired disorder in hepatic disease. A qualitatively abnormal fibrinogen was detected in the plasma of a 25-year-old man with a thrombotic tendency. The purified fibrinogen had a significantly increased content of sialic acid, an abnormal fibrin monomer polymerization, and a changed mobility in crossed affinity-immunoelectrophoresis using immobilized helix pomatia lectin. The patient had no biochemical or clinical signs of liver disease. The occurrence of a thrombotic tendency and an increased fibrinogen sialic acid content without signs of liver disease may represent a new variant of congenital dysfibrinogenaemia.

Adult↗
PubMed1983

Lowering of serum total T3 during a conventional slimming regime.

Serum concentrations of total triiodothyronine (T3) and thyroxine (T4) were determined in 28 obese out-patients before and after 12 weeks of treatment with a conventional slimming diet of 5.2 MJ (1245 kcal). Twenty-one of the patients were also given central stimulating anorectics (diethylpropion and 'Elsinore-pill' containing ephedrine). The median weight loss was 8.1 kg (range 0.4-19.1 kg). After the treatment a small, but significant (P less than 0.02), fall in serum T3 could be demonstrated whilst serum T4 was unaffected. The median fall in T3 in percentage of pretreatment value was 9 per cent (96 per cent confidence limits: 4-16 per cent). Neither serum T3 nor serum T4 correlated with the initial body weight, overweight or energy intake. In the patients treated with anorectics serum T4 was not elevated after 12 weeks, indicating that a possible sympatomimetic effect of central stimulating anorectics upon the thyroid gland is only temporary.

Adolescent↗