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Biomedical subjects

J Hansen

Publications and source records attributed to J Hansen.

At least 109 records · Page 6Linked to original sources

Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities.

Cytogenetic abnormalities in human malignancies frequently involve chromosome 7. The existence of several tumor suppressor genes on the long arm of chromosome 7 has been suggested in both epithelial and hematologic malignancies. From the Danish Cytogenetic Register, we identified 183 persons with constitutional abnormalities involving chromosome 7, including 16 patients with Williams syndrome. By linkage to the Danish Cancer Registry, we found five persons with cancer, including one thyroid carcinoma, three carcinomas of the digestive tract, and one malignant melanoma. There were no cases of leukemia. The overall risk of developing cancer was not increased.

Adult↗

Effect of HLA matching on outcome of related and unrelated donor transplantation therapy for chronic myelogenous leukemia.

This article examines the diversity and biologic role of human lymphocyte antigen (HLA) genes as related to marrow transplantation for chronic myelogenous leukemia (CML). A better understanding of the nature and function of HLA variation is necessary as unrelated marrow transplantation evolves into a safe and effective treatment for CML. HLA matching is an important aspect of donor selection criteria and has a role in engraftment as well as the development of graft-versus-host disease and tolerance after transplant.

Bone Marrow Transplantation↗

Morbidity in Turner syndrome.

Turner syndrome afflicts approximately 50 per 100,000 females and is characterized by retarded growth, gonadal dysgenesis, and infertility. Much attention has been focused on growth and growth promoting therapies, while less is known about the natural course of the syndrome, especially in adulthood. We undertook this study to assess the incidence of diseases relevant in the study of Turner syndrome. The study period was from January 1, 1984 to December 31, 1993, and the study base was all women living in Denmark during the study period. We used data from the Danish Cytogenetic Central Register and the Danish National Registry of Patients to assess morbidity. This study supports several earlier studies reporting increased morbidity and confirms results of a recent study on cancer in Turner syndrome. Women with Turner syndrome seem to have an increased incidence of fractures, osteoporotic fractures in adulthood, and non-osteoporotic fractures in childhood. Furthermore, diabetes mellitus, both NIDDM and IDDM, was found with a markedly increased incidence in Turner syndrome, as well as ischemic heart disease, hypertension, and stroke. The risk of cancer, except cancer of the large bowel, does not seem to be elevated in Turner syndrome. Our data suggest that patients with Turner syndrome are extraordinarily prone to abnormalities constituting the metabolic syndrome (e.g., hypertension, dyslipidaemia, NIDDM, obesity, hyperinsulinemia and hyperuricemia). The present data may help to explain the decreased life span found in patients with Turner syndrome.

Adolescent↗

Bioadhesive drug delivery systems. I. Characterisation of mucoadhesive properties of systems based on glyceryl mono-oleate and glyceryl monolinoleate.

A group of fatty acid esters capable of forming liquid crystals has been identified as a new class of potential bioadhesive substances. The liquid crystals may act as a controlled release system. The experimental work was focused on the monoglycerides, glyceryl mono-oleate (GMO) and glyceryl monolinoleate (GML). The mucoadhesive properties of GMO and GML were demonstrated in vitro by a 'flushing' bioadhesion test system and a tensiometric method. The flushing system was validated with GMO. Mucoadhesion is influenced by the drug and excipient added, their concentrations, and the ability to form especially the cubic phase. It has been shown that the cubic phase is mucoadhesive when formed on wet mucosa, such as rabbit jejunum, and that drug added to the precursor formulation is incorporated in the cubic phase formed. Tensiometric measurements have shown that the unswollen monoglycerides have the greatest mucoadhesion, followed by the partly swollen lamellar phase and the fully swollen cubic phase. The values found for the work of adhesion were in the range 0.007-0.048 mJcm-2. The mechanism of mucoadhesion is unspecific and probably involves dehydration of the mucosa. The cubic phase of GMO and GML may be an interesting candidate for a bioadhesive drug delivery system.

Adhesiveness↗

Lung cancer mortality among European rock/slag wool workers: exposure-response analysis.

OBJECTIVES: The purpose was to analyze the relationship between semi-quantitative indices of exposure to manmade vitreous fibers and lung cancer mortality among European rock/slag wool (RSW) workers. METHODS: The study population comprised 9,603 male workers employed in RSW production in seven factories in Denmark, Norway, Sweden, and Germany, followed up for mortality as of 1990-91. Estimates of past exposure to respirable fibers were used to calculate cumulative exposure with a 15-year lag and maximum annual exposure based on employment history up to 1977. Rate ratios were estimated via multivariate Poisson regression, adjusting for country, age, calendar year, time since first employment, and employment status. RESULTS: A total of 159 lung cancer deaths were included in the analysis of which 97 among workers with more than one year of employment. We found nonstatistically significant trends in lung cancer risk according to cumulative exposure. Relative risks (RR) in the four quartiles were 1.0 (reference), 1.3 (95 percent confidence interval [CI] = 0.8-2.4), 1.2 (CI = 0.7-2.1), and 1.5 (CI = 0.7-3.0, P test for trend = 0.4). When workers with less than one year of employment were excluded, there was no increased risk; the RRs in the four quartiles were 1.0, 0.9 (CI = 0.4-2.0), 0.8 (CI = 0.3-1.9), and 1.0 (CI = 0.4-2.7). No trend was present according to maximum annual exposure. The results were not consistent among countries. CONCLUSIONS: We found a positive association between exposure to respirable fibers and lung cancer mortality. However, the lack of statistical significance, the dependence of the results on inclusion of short-term workers, the lack of consistency among countries, and the possible correlation between exposure to respirable fibers and to other agents reduce the weight of such evidence.

Adult↗

Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen.

The gp120-derived V3 loop of HIV-1 is involved in co-receptor interaction, it guides cell tropism, and contains an epitope for antibody neutralization. Thus, HIV-1 V3 is an attractive vaccine candidate. The V3 of the MN strain (MN V3) contains both B- and T-cell epitopes, including a known mouse H-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2 + S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation by gene gun was used for genetic immunization in a mouse model. Antibody and CTL responses to MN V3 and HBsAg were measured and compared with the immune responses obtained after vaccination with plasmids encoding the complete HIV-1 MN gp160 and HBsAg (pre-S2 + S), respectively. DNA vaccination with the HIV MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a 'genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HBsAg plasmid constructs may be useful in DNA immunizations as a 'carrier' of protein regions or minimal epitopes which are less exposed or poorly immunogenic.

AIDS Vaccines↗

Comparisons of DNA-mediated immunization procedures directed against surface glycoproteins of human immunodeficiency virus type-1 and hepatitis B virus.

DNA vaccination methods were compared to examine the in vivo expression of HIV-1 gp160 and beta-galactosidase, and the resulting immune response. Beta-galactosidase plasmid showed expression rates of 2-5% of muscle fibers with or without pretreatments using bupivacaine or cardiotoxin facilitators 1 or 5 days earlier, respectively. In contrast, HIV gp160 expression was lower in untreated or bupivacaine-treated muscles, but was improved by pretreatment with cardiotoxin. Equal expression of beta-galactosidase and HIV gp160 was obtained using gene gun delivery to the epidermis. Unlike the i.m. in situ expression of gp160, the anti-HIV antibody response did not improve after muscle pretreatments but depended on the vaccination intervals. Gene gun delivery of pMN160 also resulted in a slow and low titered antibody response. In contrast, a single i.m. injection of plasmid encoding another viral envelope, HBsAg, resulted in earlier seroconversion to high titers without the need for pretreatments or boostings. Intradermal inoculation by gene gun using 100-fold less DNA resulted in the same anti-HBsAg antibody profile only after boostings. In contrast to the differences in antibody responses, a specific CTL response was obtained in all cases. Bupivacaine-treated muscles showed an extreme degree of edema with disruption of connective tissue (endo- and mesomysium) and was not well tolerated (4 of 19 mice died). Cardiotoxin created muscle necrosis and occasional (2 of 20 mice) development of fibrotic muscles. It is concluded that in vivo expression cannot be properly predicted using reporter gene experiments and that the resulting immune response does not follow directly with the expression rate. It is suggested that the antibody response may depend primarily on the nature of the antigen expressed rather than the DNA vaccination method. It is proposed that gene gun or i.m. injection be used without pretreatment in the case of DNA vaccination with plasmid encoding HIV MN gp160.

AIDS Vaccines↗

New hybrids between Saccharomyces sensu stricto yeast species found among wine and cider production strains.

Two yeast isolates, a wine-making yeast first identified as a Mel+ strain (ex. S. uvarum) and a cider-making yeast, were characterized for their nuclear and mitochondrial genomes. Electrophoretic karyotyping analyses, restriction fragment length polymorphism maps of PCR-amplified MET2 gene fragments, and the sequence analysis of a part of the two MET2 gene alleles found support the notion that these two strains constitute hybrids between Saccharomyces cerevisiae and Saccharomyces bayanus. The two hybrid strains had completely different restriction patterns of mitochondrial DNA as well as different sequences of the OLI1 gene. The sequence of the OLI1 gene from the wine hybrid strain appeared to be the same as that of the S. cerevisiae gene, whereas the OLI1 gene of the cider hybrid strain is equally divergent from both putative parents, S. bayanus and S. cerevisiae. Some fermentative properties were also examined, and one phenotype was found to reflect the hybrid nature of these two strains. The origin and nature of such hybridization events are discussed.

Alleles↗

Increased risk of lung cancer among different types of professional drivers in Denmark.

OBJECTIVES: To study risk of lung cancer among groups of professional drivers probably exposed to different levels of traffic exhaust fumes. METHODS: A nationwide case-control study (1970-89) based on employees comprising 28,744 men with primary lung cancer and incidence density sampled matched controls (1:1). Employment histories were reconstructed back to 1964 for each study subject from the records of a nationwide pension scheme with compulsory membership. Socioeconomic status was derived from the individual job title taken from the national population registry. Information on tobacco smoking habits was available from historical surveys. Relative risks were estimated by odds ratios (ORs) based on conditional logistic regression analyses. RESULTS: In total 2251 of the male lung cancer cases had been employed as bus, lorry, taxi, or unspecified drivers. No significant difference in tobacco smoking habits was found among professional male Danish drivers and the total employed population. The OR for lung cancer adjusted for socioeconomic status was 1.6 (95% confidence interval (95% CI) 1.2 to 2.2) among taxi drivers, who were considered to be exposed to the highest concentrations of vehicle exhaust fumes, and 1.3 (1.2 to 1.5) for bus and lorry drivers. The OR was 1.4 (1.3 to 1.5) for unspecified drivers. The adjusted risk of lung cancer increased significantly with increasing duration of employment as a driver, and the risk was highest for long term taxi drivers with 10 years of lag time (OR 3.0; 1.2 to 6.8). CONCLUSION: Occupational factors, probably exposure to vehicle exhaust, seems to play an important part in the development of lung cancer among drivers.

Adolescent↗

Environmental exposure to crocidolite and mesothelioma: exposure-response relationships.

This study aimed to estimate exposure-response relationships for mesothelioma and environmental exposure to crocidolite. All 4,659 former residents of Wittenoom, Western Australia (WA) who lived there between 1943 and 1993 for at least 1 mo and were not directly employed in the crocidolite industry, were followed-up through the WA death, cancer and mesothelioma registries, electoral rolls, and telephone books. In 1992, all subjects who should be traced were sent a questionnaire. Exposure levels were estimated from results of periodic environmental surveys and duration of residence. Incidence rates were standardized to the World Population and Cox Regression was used to estimate the effects of exposure on incidence. To the end of 1993, 27 cases of mesothelioma were diagnosed. Mesothelioma cases stayed longer at Wittenoom, had a higher average intensity of exposure, and a higher cumulative exposure to crocidolite than control subjects. The standardized incidence of mesothelioma was 260 per million person-years, and was similar for males and females. The rate increased significantly with time from first exposure, duration of exposure and cumulative exposure. At these levels of crocidolite exposure, there is a significantly increased risk of mesothelioma, which is dose-dependent.

Adult↗

Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer.

PURPOSE: To evaluate the influence of cumulative dose, dose-intensity, single-dose level, and schedule of epirubicin on the risk of developing congestive heart failure (CHF) in patients with advanced breast cancer. PATIENTS AND METHODS: Four hundred sixty-nine consecutive anthracyline-naive patients with metastatic breast cancer were included. Only patients with cardiac failure according to New York Heart Association (NYHA) function class II or more were recorded as having CHF. For each patient, the following were calculated: the cumulative dose of epirubicin, mean dose-intensity (cumulative dose of epirubicin/duration of treatment), and single-dose level (cumulative dose of epirubicin/number of injections). RESULTS: Thirty-four patients (7.2%) developed CHF. The cumulative risk of cardiotoxicity was 4% at 900 mg/m2 and increased exponentially to 15% at 1,000 mg/m2. Irradiation against the mediastinum and thoracic spine increased the risk of CHF (P=.025), but dose-intensity, single-dose level, and schedule had no influence on the risk of developing CHF. Age, previous adjuvant irradiation (to the left or right hemithorax), and previous chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) were not risk factors. The median time to onset of CHF following the last dose of epirubicin was 57 days (range, 0 to 853). Among patients with CHF, 13 (38.2%) died of cardiac failure. The median survival time for all patients with CHF was 162 days (range, 0 to +1,957). Previous irradiation directly against the heart increased the risk of death due to cardiac failure and decreased the median survival time to 125 days (range, 0 to 336). CONCLUSION: The present large retrospective study of 469 patients substantiates previous results concerning the cardiotoxicity of epirubicin. A significantly increasing risk of CHF in patients who receive cumulative doses greater than 950 mg/m2 was established. The future recommended maximum cumulative dose of epirubicin should be 900 mg/m2 in patients with metastatic breast cancer. Previous irradiation against the heart leads to an increased risk of developing CHF with an accelerated course to death, which indicates an additive cardiotoxic effect of irradiation and epirubicin.

Adult↗

Common cancers in the elderly.

The proportion of elderly persons (65 years or older) has increased in most countries during the last few decades, and will increase further in the coming years. Annual age-standardised cancer incidence rates per 100,000 elderly persons (1988 to 1992) were calculated based on data from cancer registries in 51 countries in 5 continents kept by the International Agency for Research on Cancer (IARC) and International Association of Cancer Registries (IACR). The proportions of all cancers among elderly men and women were 61 and 56% respectively. All cancers combined (except nonmelanoma skin cancer) were, based on the standardised rates, almost 7-fold more frequent among elderly men (2158 per 100,000 person-years), and around 4-fold more frequent among elderly women (1192 per 100,000 person-years) than among younger persons (30 to 64 years old). However, large variations exist between different cancer sites. Contrary to the pattern in younger age groups, in which annual cancer rates are almost equally distributed among the 2 genders, elderly men have an almost double cancer incidence rate compared with elderly women. For all major specific cancer sites except testicular cancer, the incidence rate is significantly higher among the elderly than among any groups of younger and middle-aged persons. Among elderly men, cancer of the prostate (451 per 100,000), the lung (449 per 100,000) and the colon (176 per 100,000) make up around half of all diagnosed cancers. Prostate cancer is around 22 times more frequent among elderly men than among younger men. The corresponding most frequent cancers among elderly women, making up 48% of all malignant cancers, are breast (248 per 100,000), colon (133 per 100,000), lung (118 per 100,000) and stomach cancer (75 per 100,000). For most cancers, marked geographical variations in incidence rates are found among the elderly, reflecting socioeconomic differences, particularly between the developing and the developed countries. In contrast with other major causes of death among the elderly, cancer incidence and mortality have not in general declined, indicating that primary prevention (especially cessation of tobacco smoking) remains a most valuable approach to decrease mortality; for most of the major cancers (prostate, colon, breast) the causes remain almost unknown. Thus, research into potential causes is urgently needed for future prevention. Since the mortality rates for female cancer in general are declining, and since the incidence is increasing more steeply than the mortality among the men, the number of living elderly ever diagnosed with a cancer will further increase during the next years. Therefore, it is important to emphasise the increasing need for research into the prevention of cancer and the planning of treatment and care in the elderly.

Adult↗

Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study.

PURPOSE: We evaluated the erectogenic properties of a new cyclic alpha-melanocyte-stimulating hormone analogue, Melanotan-II, to treat men with psychogenic erectile dysfunction. MATERIALS AND METHODS: Ten men with erectile dysfunction of no known organic cause were entered in a double-blind, placebo controlled crossover study in which the erectogenic properties of Melanotan-II and a vehicle placebo were compared using real-time RigiScan monitoring. The presence, duration and rigidity of erections were recorded during a 6-hour period. RESULTS: In 8 of 10 men treated with Melanotan-II clinically apparent erections developed. Mean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo (p=0.0045). Transient side effects of nausea, stretching and yawning, and decreased appetite were reported more frequently after injections of Melanotan-II than placebo but none required treatment. CONCLUSIONS: Melanotan-II is a potent initiator of erections in men with psychogenic erectile dysfunction and has manageable side effects at a dose of 0.025 mg./kg.

Abdominal Muscles↗

Expression of natural and synthetic genes encoding herpes simplex virus 1 protease in Escherichia coli and purification of the protein.

An attractive target for anti-herpes chemotherapy is the herpes simplex virus 1 (HSV-1) protease encoded by the UL26 gene. Studies with HSV-1 strains that harbour mutations in the protease gene have demonstrated that the protease is essential for DNA packaging and virus maturation. The UL26 translation product is 635 amino acids long and undergoes autoproteolytic processing between residues Ala247/Ser248 and Ala610/Ser611. The N-terminal processing product (amino acids 1-247) contains the protease domain. To perform crystallization studies and high throughput screening for potent inhibitors, large amounts of the HSV-1 protease are required. However, expression of the natural HSV-1 protease gene in Escherichia coli using a T7-promoter-regulated system is low and does not allow for the efficient production of larger amounts of highly purified enzyme. In this report, we describe the use of a synthetic protease gene with optimized E. coli codon usage. The level of protease expression was at least 20 times higher with the synthetic gene as compared to the natural UL26 gene. The HSV-1 protease was purified to homogeneity in three steps using mixed-bed ion-exchange chromatography, affinity chromatography, and hydroxyapatite chromatography.

Amino Acid Sequence↗

Determination of acetyl-CoA enrichment in rat heart and skeletal muscle by 1H nuclear magnetic resonance analysis of glutamate in tissue extracts.

The contribution of a 13C-enriched substrate to the acetyl-CoA pool in animal tissues is typically measured by analysis of glutamate enrichment from tissue extracts. 13C NMR analysis offers the advantages of minimal sample processing and high information content, but has a low analytical sensitivity compared to other methods of tracer analysis such as GC/MS. We present a sensitive, simple, and direct 1H NMR measurement of glutamate C4 enrichment from tissue extracts. The method is demonstrated with heart and hindlimb muscle tissue extracts of rats infused with [2,4,6,8-13C4]-octanoate, a source of [2-13C]acetyl-CoA. Glutamate C4 enrichment in extracts of individual hindlimb soleus muscles weighing approximately 150 mg and containing approximately 0.3 mumol of glutamate was quantified by 1H NMR within about 40 min. Glutamate C4 enrichment measurements by 1H NMR in heart and gastrocnemius muscle were also highly correlated with independent measurements obtained from 13C NMR isotopomer analysis.

Acetyl Coenzyme A↗

ATP-sensitive potassium channels mediate contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle.

Sympathetic vasoconstriction is sensitive to inhibition by metabolic events in contracting rat and human skeletal muscle, but the underlying cellular mechanisms are unknown. In rats, this inhibition involves mainly alpha2-adrenergic vasoconstriction, which relies heavily on Ca2+ influx through voltage-dependent Ca2+ channels. We therefore hypothesized that contraction-induced inhibition of sympathetic vasoconstriction is mediated by ATP-sensitive potassium (KATP) channels, a hyperpolarizing vasodilator mechanism that could be activated by some metabolic product(s) of skeletal muscle contraction. We tested this hypothesis in anesthetized rats by measuring femoral artery blood flow responses to lumbar sympathetic nerve stimulation or intraarterial hindlimb infusion of the specific alpha2-adrenergic agonist UK 14,304 during KATP channel activation with diazoxide in resting hindlimb and during KATP channel block with glibenclamide in contracting hindlimb. The major new findings are twofold. First, like muscle contraction, pharmacologic activation of KATP channels with diazoxide in resting hindlimb dose dependently attenuated the vasoconstrictor responses to either sympathetic nerve stimulation or intraarterial UK 14,304. Second, the large contraction-induced attenuation in sympathetic vasoconstriction elicited by nerve stimulation or UK 14,304 was partially reversed when the physiologic activation of KATP channels produced by muscle contraction was prevented with glibenclamide. We conclude that contraction-induced activation of KATP channels is a major mechanism underlying metabolic inhibition of sympathetic vasoconstriction in exercising skeletal muscle.

Adrenergic alpha-Agonists↗

[Prenatal and postnatal prevalence of Turner syndrome. A registry-based study].

The prevalence of Turner's syndrome in Denmark 1970-1993 was studied and the validity of prenatal diagnosis was assessed. The study was conducted on prenatal and postnatal Turner's syndrome in the Danish Cytogenetic Central Register. All registered Turner's syndrome karyotypes (100 prenatal cases and 215 postnatal cases) at the Danish Cytogenetic Central Register were included. The main outcome measures were prevalence of Turner's syndrome karyotypes among prenatally tested fetuses and Turner's syndrome among liveborn infants. The results showed that among infant girls, prevalence of Turner's syndrome was 32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner's syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner's syndrome, pregnancy was allowed to continue and 24 of the children were live born. Thirteen of the liveborn children were karyotyped postnatally, and the diagnosis of Turner's syndrome had to be revised for eight, seven being normal girls and one boy. This gives a tentative predictive value of amniocentesis in the diagnosis of Turner's syndrome between 21% and 67%. There was no significant relation between mother's age and risk of Turner's syndrome. In conclusion, a discrepancy between prenatal and postnatal prevalence of Turner's syndrome challenges the specificity of prenatal examination in diagnosing Turner's syndrome.

Adult↗