Biomedical subjects

C Hansen

Publications and source records attributed to C Hansen.

At least 73 records · Page 4Linked to original sources

PubMed1997

Tumor selectivity and transcriptional activation by azelaic bishydroxamic acid in human melanocytic cells.

Azelaic bishydroxamic acid (ABHA), a potent differentiating agent for lymphoid cells, was selectively toxic for 5 human tumor cell lines and transformed human melanocytes and keratinocytes (dose for 37% survival, D37, 30-100 microg/mL) compared with normal cells (melanocytes, fibroblasts; D37 > 300 microg/mL). Dendritic morphology was the only indicator found for increased differentiation, markers for the pigmentation pathway being unchanged or inhibited by ABHA. In contrast to hexamethylene bisacetamide and azelaic acid, ABHA significantly increased the HIV LTR, SV40 and c-fos promoter activities during a 24 hr treatment. Metallothionein promoter activity was enhanced by 5 hr treatment with ABHA in a sensitive melanoma cell line (MM96L) but was inhibited in a more resistant line (HeLa); c-fos promoter activity was inhibited in HeLa during this time. Transcription from a p53 binding response element was inhibited in MM96L by a 24 hr ABHA treatment but enhanced in HeLa. ABHA may represent a structural prototype for designing more potent and selective anti-melanoma agents.

Acetamides↗

PubMed1997

Primary care physicians and capitated reimbursement. Experience, attitudes, and predictors.

Given the explosive expansion of capitated reimbursement for the services of primary care physicians, we conducted a national survey of a random sample of these practitioners to measure attitudes toward capitated payment and identify predictors of important attitudes. Descriptive, factor analytic, and regression techniques were used. The response rate was 54%. As measured by scales derived from factor analysis, perceptions were strong that capitation was costly to professional and patient relationships. Patients' access to care was perceived as slightly reduced. Actual participation in capitation attenuated feelings of lack of access but not those of capitation's costly effects. Physicians' attitudes toward capitation remain negative, but participants perceive their patients' access to appropriate care as reasonable.

Attitude of Health Personnel↗

PubMed1997

A methodology for biokinetic studies using stable isotopes: results of repeated molybdenum investigations on a healthy volunteer.

A method for biokinetic studies in humans using stable isotopes is presented. The technique is based on double tracer administration and on proton activation as the analytical method. As an application, the results of investigations on molybdenum metabolism in humans are reported. The contents of 95Mo and 96Mo in biological samples were determined by inducing (p,n) reactions and by analysing the gamma-rays emitted by the radioactive products. The minimum detectable quantity was 2 ng/mL plasma for both Mo isotopes. Four investigations on molybdenum metabolism were performed on a healthy volunteer subject in the course of 3 yr. Two absorption studies with different amounts of tracers in aqueous solution were performed by giving 96Mo orally and 95Mo intravenously. Two investigations were performed with single oral administration of 96Mo in aqueous solution and of a 96Mo solution mixed with an infant formula respectively. The stability with time of the biokinetic parameters was tested. The fractional absorption values measured in this volunteer were 0.84, 0.98 and 0.95 for three studies with Mo in HCl and 0.51 for a single study with Mo administered in an infant formula, these data are discussed.

Humans↗

PubMed1997

HPLC glycosaminoglycan analysis in patients with Graves' disease.

1. Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAGs) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with Graves' eye disease. 2. A highly specific method to determine the concentration and biochemical composition of different GAGs was developed in order to obtain a sensitive test system for the activity of the disease. By means of this method, GAG excretion in 24 h urine collections of 56 patients and 21 controls was analysed by precipitation with cetylpyridinium chloride and potassium acetate in ethanol, followed by sequential enzymic hydrolysis with chondroitin AC lyase, chondroitin ABC lyase and hyaluronate lyase, with HPLC analysis of the resulting alpha, beta-unsaturated disaccharides by anion-exchange chromatography. 3. Concentrations of GAG, chondroitin sulphate A (CA), dermatan sulphate (DS) and hyaluronic acid (HA) were determined in patients and controls, with high recovery rates [72.2 +/- 5.3%, mean +/- SEM; detection limit, 4.2 micrograms/l (0.01 mumol/l)], revealing marked differences in urinary concentrations of total GAG and HA, as well as an elevation of CA in patients compared with controls. 4. Method sensitivity was 0.86 for patients with active Graves' eye disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation (before therapy: GAG, 111.49 +/- 40.32; CA, 59.58 +/- 21.34; DS, 25.05 +/- 8.12; HA, 26.88 +/- 11.63 mg/24 h; during therapy: GAG, 54.22 +/- 10.94; CA, 20.52 +/- 4.58; DS, 17.65 +/- 3.46; HA, 16.05 +/- 3.69 mg/24 h), whereas GAG excretion increased markedly 2-3 months after stopping prednisone therapy in patients with still active eye disease (GAG, 109.9 +/- 10.51; CA, 63.8 +/- 7.34; DS, 24.1 +/- 5.07; HA, 22.0 +/- 6.28 mg/24 h). 5. This sensitive method determines the nature of renally excreted GAGs, reflecting the aberrant synthesis pattern of fibroblasts in patients with Graves' disease.

Acute Disease↗

PubMed1997

Diabetic microangiopathy and urinary glycosaminoglycans.

Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (< or = 10 yr: 20.8 +/- 2.1 vs > 10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (> 300 mg/24 h: 29.9 +/- 3.3 vs < 30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (> 0.5 g/24 h: 30.3 +/- 3.7 vs < 0.05 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (> 0.12 mg/L: 34.9 +/- 2.3 vs < 0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship renal GAG excretion and the presence of microangiopathy in IDDM patients.

Adolescent↗

PubMed1997

Anxious children in adulthood: a prospective study of adjustment.

OBJECTIVE: To prospectively examine psychosocial functioning in young adulthood for children and adolescents with anxiety disorders. METHOD: This 8-year prospective study compared psychosocial functioning in young adults (mean age 22 years) who had histories of early-onset anxiety disorders, comorbid anxiety and depressive disorders, or no history of psychiatric illness (NPI). Follow-up interviews assessed subjects' residential, educational, occupational, and marital status; utilization of mental health services; and psychological status RESULTS: Anxious subjects without histories of depression were less likely than NPI controls to be living independently. Anxious-depressed subjects were less likely than controls to be working or in school; more likely than purely anxious subjects to utilize mental health services; and more likely than both anxious and control subjects to report psychological problems, most frequently depression. CONCLUSIONS: Overall, results suggest that children with anxiety disorders are relatively well adjusted in young adulthood. However, a history of comorbid depression is prognostic of a more negative outcome.

Adolescent↗

PubMed1997

Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect.

Prader-Willi syndrome (PWS) is a neuroendocrine disorder caused by a non-functioning paternally derived gene(s) within the chromosome region 15q11-q13. Most cases result from microscopically visible deletions of paternal origin, or maternal uniparental disomy of chromosome 15. In both instances no recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When the imprinting mutation is inherited from a carrier father, the risk that future children will be affected is theoretically 50%. It is therefore important that these families are referred to a geneticist for counselling and further investigation. Prenatal diagnosis is currently only feasible when the mutation has been identified in the affected child.

Chromosomes, Human, Pair 15↗

PubMed1997

Biphasic response of the metallothionein promoter to ultraviolet radiation in human melanoma cells.

Because metallothionein (MT) is elevated and may be protective in UV-irradiated skin, we have studied the effects of UV and other agents on MT transcription using the sheep MT 1A promoter, linked to the beta-galactosidase gene and stably transfected into human cell lines. beta-galactosidase reporter activity was inducible by adding Zn2+ ions to the medium (100 microM for 2-4 h). Two differentiating agents, butyric acid and azelaic bishydroxamic acid (ABHA), significantly increased the response to Zn2+ in a melanoma cell line (MM96L-gal). UVB (280-315 nm) had two distinct, time-dependent effects. During the first 4 h after irradiation, high doses of UVB inhibited induction by Zn2+, an effect that was made more acute by simultaneous exposure to the differentiating agents. These changes in reporter activity were not due to alterations in Zn2+ transport into the cell. The UVB-depressed MT response subsequently recovered and by 24 h was double the control, yet remained sensitive to ABHA. Reporter activity in transfected HeLa cells differed from that in MM96L, being depressed 4 and 24 h after UVB and insensitive to ABHA at both times. Galactosidase reporter activity driven by non-MT promoters was not affected by these treatments. Dependence of MT transcriptional activity on UV-related DNA damage could be inferred because equitoxic UVC (254 nm) affected the response to Zn2+ in a similar fashion, whereas UVA, cisplatin and a methylating agent had no effect. The MT response was partly dependent on the PKC signal transduction pathway because it was inhibited by phorbol ester in HeLa, and by bisindolyl maleimide in HeLa and MM96L. The biphasic MT transcriptional response may model a signal transduction pathway that gives an early, depressed response to acute UV damage, with exacerbation by concurrent differentiation stimuli, but switches to a positive, cell-specific and potentially protective response at later times.

Animals↗

PubMed1997

Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial.

OBJECTIVE: Vitamin E, the most potent naturally occurring lipid soluble antioxidant has been suggested to possess both anti-inflammatory and analgesic activity in humans. This double blind and randomised study used a broad spectrum of clinical and laboratory parameters to investigate whether there was any additional anti-inflammatory or analgesic effects, or both, of orally administered alpha-tocopherol in rheumatoid arthritis patients who were already receiving anti-rheumatic drugs. METHODS: Forty two patients were enrolled and treated with alpha-tocopherol (n = 20) at a dose of 600 mg twice a day (2 x 2 capsules) or with placebo (n = 22) for 12 weeks. The following parameters were measured: (1) Three clinical indices of inflammation--the Ritchie articular index, the duration of morning stiffness, and the number of swollen joints; (2) three measures of pain--pain in the morning, pain in the evening, and pain after chosen activity; (3) haematological and biochemical measures of inflammatory activity; (4) assays for the oxidative modification of proteins and lipids. RESULTS: All laboratory measures of inflammatory activity and oxidative modification were unchanged. Furthermore, the clinical indices of inflammation were not influenced by the treatment. However, the pain parameters were significantly decreased after vitamin E treatment when compared with placebo. CONCLUSION: The results provide preliminary evidence that vitamin E may exert a small but significant analgesic activity independent of a peripheral anti-inflammatory effect, but which complements standard anti-inflammatory treatment.

Administration, Oral↗

PubMed1997

Prevalence of dissociative disorders in an acute care day hospital population.

To estimate the prevalence of dissociative disorders in a day hospital and examine their relation to traumatic experiences, trained clinicians evaluated 70 of 229 patients consecutively admitted to an acute care day hospital. They used the Mini-Structured Clinical Interview for DSM-III-R Dissociative Disorders and the Traumatic Experience Questionnaire. Six of the 70 patients (9 percent) received a definite diagnosis of a dissociative disorder. Five of the six patients reported a childhood history of sexual or physical abuse. The results show that dissociative disorders are not rare among general psychiatric patients in a day hospital setting and are associated with histories of childhood trauma.

Adult↗

PubMed1996

Laser-evoked potentials after painful hand and foot stimulation in humans: evidence for generation of the middle-latency component in the secondary somatosensory cortex.

The vertex potential (N2, P2) of the laser-evoked potential (LEP) is preceded by a small negativity (N1). The role of the secondary somatosensory cortex (SII) in generation of the N1 is established for the upper but not for the lower limb. We therefore investigated the N1 after painful radiant heat stimulation of hand and foot dorsum in 22 subjects. LEPs were recorded from the scalp with midline and temporal electrodes. After hand stimulation N1 was maximal in the contralateral temporal lead (mean peak latency 156 +/- 23 ms). After foot stimulation N1 was maximal in the same lead (200 +/- 22 ms). In the ipsilateral temporal lead, N1 appeared significantly smaller and later. N2 and P2 were maximal in midline electrodes for both stimulus sites. The latency shift between hand and foot stimulation was identical for all three components. These results suggest a contribution of temporo-parietal cortex (e.g. SII) to the N1 generation for stimulation of upper and lower limb.

Adult↗

PubMed1996

Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10.

Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN. +/op) F1 carriers, we mapped this locus by linkage analysis with microsatellite markers to rat chromosome 10. The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]-1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog-2, and proline-rich protein). The markers for these loci include nine not previously reported. The op locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its location, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect.

Animals↗

PubMed1996

Intestinal calcium absorption from different calcium preparations: influence of anion and solubility.

Not only is the calcium content of a preparation significant for providing adequate calcium supplementation for the prophylaxis and therapy of osteoporosis, but also its bioavailability is of essential importance. In the present study, the bioavailability of calcium citrate and calcium lactogluconate/carbonate from a therapeutic dose (= 500 mg Ca2+) was compared in men aged between 45 and 60 years on an intra-individual basis. Calcium citrate was administered both as a solution and as a suspension to 18 healthy volunteers. Using a double-isotope method, the intestinal absorption from the three preparations was determined in randomized order at intervals of 2-4 weeks. The stable isotope 44Ca (20 mg), in highly enriched form, was added in each case to the ready-to-drink solutions and, at the same time, a sterile and pyrogen-free solution containing 5 mg of the stable isotope 42Ca was injected intravenously. The intestinal calcium absorption was then determined after 24 h on the basis of the ratio of the two isotopes in the plasma. There was a significantly higher absorption of 29% from the citrate solution than from the lactogluconate/carbonate solution (25%). Absorption from the citrate suspension was similar to that from the lactogluconate/carbonate solution. While no correlation was found between the measured values for calcium absorption from the three preparations and the plasma concentration of 1,25-dihydroxycholecalciferol, significant inverse correlations with the basal parathyroid hormone concentration were observed for the citrate and lactogluconate/ carbonate solution. The results of this study show that quantitative data on intestinal calcium absorption can be obtained without employing radioactive isotopes in humans. Moreover, they show that calcium absorption is not determined only by the solubility and the degree of ionization of the calcium salt administered, but rather that it is of a complex nature.

Biological Availability↗

PubMed1996

No mutations found by RET mutation scanning in sporadic and hereditary neuroblastoma.

Neuroblastoma occasionally occurs in diseases associated with abnormal neurocrest differentiation, e.g. Hirschsprung disease. Expression studies in developing mice suggest that the proto-oncogene RET plays a role in neurocrest differentiation. In humans expression of RET is limited to certain tumor types, including neuroblastoma, that derive from migrating neural crest cells. Mutations of RET are found associated with Hirschsprung disease. These data prompted us to investigate expression of RET and to search for gene mutations in neuroblastoma. Out of 16 neuroblastoma cell lines analyzed, 9 show clear expression of RET in a Northern blot analysis. In a single strandt conformation polymorphism (SSCP) analysis of all exons, no mutations were detected other than neutral polymorphisms. In a patient with neuroblastoma, from a family in which different neurocrestopathies, including neuroblastoma and Hirschsprung disease, had occurred, we also failed to detect RET mutations. Possibly, expression of RET in neuroblastoma merely reflects the differentiation status of the tumor cells. The absence of mutations suggests that RET does not play a crucial role in the tumorigenesis of neuroblastoma.

Drosophila Proteins↗

PubMed1996

Exclusion of SNRPN as a major determinant of Prader-Willi syndrome by a translocation breakpoint.

The predominant genetic defects in Prader-Willi syndrome (PWS) are 15q11-q13 deletions of paternal origin and maternal chromosome 15 uniparental disomy (UPD). In contrast, maternal deletions and paternal chromosome 15 UPD are associated with a different neurogenetic disorder, Angelman syndrome (AS). In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q11-q13 loci. The critical PWS region has been narrowed to a approximately 320-kb region between D15S63 and D15S174, encoding several imprinted transcripts, including PAR5, IPW, PAR1 (refs 7,8) and SNRPN, which has so far been considered a strong candidate for the PWS gene. A few PWS-associated microdeletions involving a putative imprinting centre (IC) proximal to SNRPN have also been observed. We have mapped the breakpoint of a balanced translocation (9;15)pat associated with most of the PWS features between SNRPN and IPWIPAR1. Methylation and expression studies indicate that the paternal SNRPN allele is unaffected by the translocation, while IPW and PAR1 are unexpressed. This focuses the attention on genes distal to the breakpoint as the main candidate for PWS genes, and is consistent with a cis action of the putative IC, and suggests that further studies of translocational disruption of the imprinted region may establish genotype-phenotype relationships in this presumptive contiguous gene syndrome.

Adolescent↗

PubMed1996

T cells and orbital connective tissue in endocrine orbitopathy.

In order to analyse the immunological changes in patients with endocrine orbitopathy (EO) the antigenic character of orbital connective tissue was studied. Counter-stimulation assays of patients' lymphocytes with autologous retrobulbar fibroblasts resulted in a markedly increased lymphocyte proliferation in comparison to incubation with retrobulbar control fibroblasts. Proliferation tests of retrobulbar T cell lines showed significant responses to autologous retro-orbital connective tissue proteins, with molecular weights of 6-10 kD and 19-26 kD. Phenotypic analysis of orbital T cell lines indicates that they consisted predominantly of CD4+ cells. Hyaluronic acid production of orbital fibro blasts following co-cultivation with lymphocytes of EO patients or controls revealed a threefold increased synthesis in patients with EO. Furthermore, distribution pattern of orbital extracellular matrix glycosaminoglycans (GAG) differs in EO patients in comparison to controls. The results suggest the presence of autoreactive T cells directed against antigens of orbital fibroblasts, whose stimulation results in an augmented GAG synthesis in patients with EO.

Connective Tissue↗

PubMed1996

The acute impact of ethanol on glucose, insulin, triacylglycerol,and free fatty acid responses and insulin sensitivity in type 2 diabetes.

The aim of the present study was to evaluate the acute effect of ethanol on insulin sensitivity, and glucose, insulin, free fatty acid (FFA), and triacylglycerol responses in ten patients with non-insulin-dependent (type 2) diabetes. In the test study an oral dose of 0.66 g ethanol/kg followed by continuous intravenous infusion of 0.1 g ethanol/kg per h was given to maintain a constant ethanol level in the blood. In the control study identical volumes of oral water and intravenous saline (9 g NaCl/l) were given. After 90 min insulin sensitivity was determined by the hyperinsulinaemic, euglycaemic clamp technique. Ethanol caused no change in blood glucose or insulin concentrations. The FFA level was suppressed by ethanol while the triacylglycerol level was unaffected. The insulin sensitivity was not affected by ethanol. No major acute effect of ethanol on the glycaemic control in fasting type 2 diabetic patients was found in comparison with what is seen in healthy people. The present study, along with the sparse literature, indicates that the ability of ethanol to induce hypoglycaemia is attenuated or absent in diet-treated type 2 diabetes. Furthermore, we found no change in insulin sensitivity. Consequently, the risk of acute ethanol-induced aberrations in carbohydrate metabolism in diet-treated type 2 diabetes seems to be less than previously expected, when alcohol is not taken as a part of a meal.

Administration, Oral↗

PubMed1996

Paradoxical heat sensation in patients with multiple sclerosis. Evidence for a supraspinal integration of temperature sensation.

Temperature thresholds were determined in 16 patients with probable or definite multiple sclerosis, in six patients with possible but unconfirmed multiple sclerosis and in 34 healthy subjects, using the method of limits and the thermal sensory limen (TSL) of the MarStock technique. A significant proportion of the patients had thresholds outside the 2.5 SD range for normal subjects, both for warmth detection threshold and TSL. In addition, 10 patients with probable or definite multiple sclerosis and one patient with possible multiple sclerosis reported a paradoxical heat sensation, i.e. a sensation of warmth elicited by a cold stimulus. This illusion was almost exclusively observed with the alternating warm and cold stimuli of the TSL procedure. In contrast to experimental nerve block or peripheral demyelinating neuropathy, where paradoxical heat sensation has been described by various authors, in the patients with multiple sclerosis the demyelination sites were located in the central nervous system. The observation that multiple sclerosis patients had paradoxical heat sensation in addition to threshold abnormalities supports the view that supraspinal sites are important for the integration of temperature sensation.

Adult↗