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Biomedical subjects

B S Hansen

Publications and source records attributed to B S Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Nutrition therapy in 542 hospitalized patients].

The purpose of the study was to evaluate the feasibility of nutritional therapy in a university hospital. Over a four-year period, 542 adult patients from 16 different departments were included in the study due to malnutrition and/or severe disease. Energy requirement including a surplus for weight gain was calculated by the factorial method and feeding was undertaken by means of food, liquid supplements, tube feeding or parenteral nutrition for an average period of 4.8 weeks. In patients with benign disease only, the average weight gain was as expected from energy balance but in patients with a benign stress-catabolic disease weight gain was only 40% of that expected. In malnourished patients with malignant disease, radiation- or chemotherapy could be carried out without further loss of body weight. During bone-marrow transplantation only a minor weight loss occurred. In conclusion, nutritional therapy is feasible in a clinical setting and the methods employed can identify groups of patients that require only nutritional support and other groups of patients that in addition require treatment of a stress-catabolic state.

Adult↗
PubMed1996

Importance of colonic support for energy absorption as small-bowel failure proceeds.

Digestive processes in the human colon are affected by the bacterial fermentation of malabsorbed carbohydrates and protein to short-chain fatty acids, which are absorbed and supply energy. Energy absorption was measured by assessing fecal bomb calorimetry in 148 patients with extremely different small-bowel lengths. Colectomy increased fecal loss of energy by 0.8 MJ/d and carbohydrate excretion fivefold in patients with a small-bowel length between normal and 150-200 cm. Patients with 100-150 cm small bowel, with and without a colon, excreted 1.3 +/- 0.3 and 4.7 +/- 0.5 MJ/d, respectively (P = 0.002), a difference of 3.4 MJ/d. Patients with < 100 cm small bowel excreted 3.1 +/- 0.4 and 8.0 +/- 1.3 MJ/d, respectively (P = 0.03), a difference of 4.9 MJ/d. Similar and highly significant differences were calculated by linear-regression analysis. Considerably less energy was excreted as carbohydrate than as fat in patients with preserved colonic function, probably because fermentation removed carbohydrate as absorbed short-chain fatty acids, whereas a comparable amount of energy was lost as carbohydrate and fat in patients without colonic function. The correlation between malabsorbed energy and small-bowel length was poor (r = -0.41) but increased when data for patients with and without a colon were separated (r = -0.56 and r = -0.58, respectively). Small-bowel length, however, was still an inaccurate measure of intestinal failure to absorb nutrient energy. In conclusion, colonic digestion may support energy supply with up to approximately 4.2 MJ/d as small-bowel failure proceeds, but it is of minor importance in patients with a small-bowel length > 200 cm or malabsorption < 2.1 MJ/d.

Adolescent↗
PubMed1996

Dopaminergic regulation of gonadotrophin secretion in seasonally anoestrous mares.

We have previously demonstrated that daily administration of the dopamine D2 antagonist, sulpiride, during seasonal anoestrus, effectively advances the mean time of onset of the breeding season in mares. The purpose of this study was to examine the effect of sulpiride administration on pulsatile FSH and LH secretion in seasonally anoestrous mares, follicular development, time of first ovulation and the fertility at the first ovulation. Fourteen anoestrous mares were selected based on progesterone concentrations < 1 ng ml-1 for 3 weeks and largest follicle diameter < 20 mm. Starting 30 January, eight seasonally anoestrous mares were treated daily with sulpiride until the first ovulation of the year, and six untreated control mares were maintained under the same environmental conditions. Ovarian activity was monitored and plasma samples were collected every other day. On days 1, 11 and 21 of treatment, plasma samples were collected every 15 min for 11 h in six treated and six control mares. Mares were bred during the first oestrus. Mean time of first ovulation was significantly advanced in sulpiride-treated mares compared with control mares. Pregnancy rate 18 days after ovulation was similar between groups. Mean FSH pulse frequency on the first day of treatment and mean plasma FSH concentrations on day 11 of treatment were significantly higher in sulpiride-treated mares compared with control mares. No significant difference was observed between groups for parameters of LH pulsatile secretion. The results of this study suggest that dopamine inhibits FSH pulsatile secretion in seasonally anoestrous mares.

Anestrus↗
PubMed1995

Colonic fermentation of complex dietary carbohydrates in short-bowel patients. No association with hydrogen excretion and fecal and plasma short-chain fatty acids.

BACKGROUND: The colonic degradation of carbohydrates (fermentation) to short-chain fatty acids (SCFAs) appears to have major impacts on colonocyte function, sodium and water absorption, and large-bowel energy salvation, but how to quantify the in vivo fermentation in man is still debatable. METHODS: Indicators of colonic fermentation, fecal and plasma SCFAs and breath hydrogen (H2), were measured in 10 short-bowel patients (mean +/- SE; 106 +/- 21 cm) with totally preserved large bowels who were on a 60% high-carbohydrate, 20% low-fat diet, compared with the reversed isocaloric 20% low-carbohydrate, 60% high-fat diet. This human model showed large differences in large-bowel fermentation, as excretions of calories were reduced (40%; 485 +/- 151 kcal/day) and excretions of carbohydrates were unchanged and low with the high-carbohydrate diet as compared with the low-carbohydrate diet, in contrast to unchanged calorie excretion in short-bowel patients with no colonic function. RESULTS: Fecal concentrations of SCFAs did not change when the diet was changed from the high content to the low content of carbohydrates (82 +/- 11 mmol/l and 79 +/- 9 mmol/l, respectively). The ratio of acetate in feces increased (from 48 +/- 4% to 54 +/- 3%; p = 0.01) on the high-carbohydrate diet, whereas the percentage of the other SCFAs decreased proportionally. Plasma SCFAs 2 h and 6 h after breakfast were also identical when comparing the two dietary regimens. Nor were the peak H2 breath excretion and the area under the H2 excretion-versus-time curve increased by the threefold increase in the intake of dietary carbohydrates. CONCLUSIONS: Fecal and plasma SCFAs and breath H2 excretion are of limited value in the evaluation of even large differences in colonic fermentation of complex dietary carbohydrates.

Adult↗
PubMed1994

Colon as a digestive organ in patients with short bowel.

Patients with a short bowel malabsorb dietary nutrients with loss of calories and weight. Malabsorbed carbohydrates are fermented by colonic bacteria to short-chain fatty acids, which are absorbed and supply energy. The maximum energy-consumption capacities in patients with short bowel were individually measured on 40:40% carbohydrate:fat diets. 8 patients with colon in continuity and 6 patients with jejunostomies were placed on isocaloric 60:20% or 20:60% carbohydrate:fat diets and faecal excretions of calories, carbohydrates, fat, nitrogen, and fluids were compared. The high-carbohydrate low-fat diet reduced faecal loss of energy by 2.0 MJ/day compared to the low-carbohydrate high-fat diet in patients with colon in continuity, and absorption of energy increased from 49 to 69% (p < 0.001). Faecal excretions of carbohydrates were low and not influenced by the change in carbohydrate intakes (26 g/day and 28 g/day, respectively) whereas faecal fat (46 g/day and 106 g/day) was highly dependent on dietary intakes and accounted for differences in faecal loss of energy. In contrast, patients with jejunostomies excreted equal amounts of calories on the high-carbohydrate diet (4.8 MJ/day) and the high-fat diet (5.9 MJ/day; p = 0.08); and the percentage of calories absorbed was not different (55% and 48%, respectively; p = 0.21). Furthermore, in patients without colon the excretions of carbohydrates (80 g/day and 42 g/day on high-carbohydrate and low-carbohydrate diets, respectively) and fat (69 g/day and 35 g/day on high-fat and low-fat diets, respectively) were proportional to the amounts ingested. The large intestine is important in the digestion of carbohydrates and hence in the salvage of calories in patients with short bowel and severe malabsorption.

Adult↗
PubMed1994

Gene transfer into cultured human epidermis and its transplantation onto immunodeficient mice: an experimental model for somatic gene therapy.

To try epidermis as a target for somatic gene therapy we studied transfected primary human keratinocytes grown in culture and grafted onto athymic mice. We have developed a novel technique for grafting cultured epidermal sheets onto mice. First, the graft is placed on the dorsal muscle fascia underneath the mouse skin using the latter as a bandage. Secondly, the mouse skin above the graft is removed, which exposes the grafted skin to open air and thus stimulates terminal differentiation. A novel method for the discrimination between murine and human epidermal cells is also presented, employing in situ hybridization with human Alu repeated DNA sequences. During monolayer culture the keratinocytes were lipofected with the gene for human growth hormone in an Epstein-Barr virus-based expression vector. The cells were allowed to develop a multilayered tissue for 5 d, secreting human growth hormone into the medium at a daily rate of at least 50 ng/cm2 of tissue. The transfected tissues were then grafted onto mice. We detected human growth hormone at levels of up to 2.6 ng/ml in mouse serum for 4 d, but later no human growth hormone could be found, although the transplants survived for months. To investigate the fate of the transfected cells in the transplanted tissue, we labeled them with the beta-galactosidase reporter gene. The cells staining positive for X-gal were found exclusively in the most superficial differentiated layers at 7 d after transplantation. This may be the main reason why no human growth hormone is found in the mouse circulation at this time.

Animals↗
PubMed1994

Pharmacological characterization of a biosynthetic trisulfide-containing hydrophobic derivative of human growth hormone: comparison with standard 22 K growth hormone.

Growth hormone is the classical anabolic hormone which promotes organ growth after binding to somatogenic target cell receptors, present in various target tissues. The present study elucidated the pharmacological characteristics in vitro and in vivo of human growth hormone and a recently identified by-product of a recombinant human growth hormone preparation; i.e. a trisulfide-containing (cys 182-cys 189) hydrophobic, folding derivative of growth hormone, hydrophobic derivative-growth hormone. Standard growth hormone and hydrophobic derivative-growth hormone possessed similar characteristics in vitro, both as regards binding to the somatogenic receptor on the human IM-9 cell line, and the prolactin receptor-mediated proliferation of rat Nb2 cells. This indicates that no change occurs in the binding characteristics in spite of a change in conformation of the molecule. Using an ELISA assay that detected standard and hydrophobic derivative-growth hormone equally well, the plasma pharmacokinetical profiles of the preparations following a single intravenous or subcutaneous dose were indistinguishable. Thus, following initial disposition of hydrophobic derivative-growth hormone and standard growth hormone into a volume, V1, of one to two times the plasma volume, almost 90% of either compound disappeared from plasma during the alpha-phase of the plasma decay curve. Similar half-lives of 4-5 min. were found for hydrophobic derivative-growth hormone and standard growth hormone during this phase, indicating rapid removal of drug from the circulation. Also, the AUC and Cmax values for standard and hydrophobic derivative-growth hormone did not differ following intravenous or subcutaneous administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The growth hormone (GH)-binding protein cloned from human IM-9 lymphocytes modulates the down-regulation of GH receptors by 22- and 20-kilodalton human GH in IM-9 lymphocytes and the biological effects of the hormone in Nb2 lymphoma cells.

The cDNA coding for the 246-amino acid long N-terminal extracellular portion of the human (h) GH receptor, corresponding to the circulating GH-binding protein (hGHBP), was cloned by polymerase chain reaction from human IM-9 lymphocytes. The cDNA sequence was identical to that reported for human liver and placenta and demonstrated alternative splicing of exon 3. The protein with the exon 3-encoded domain was expressed and secreted in glycosylated form from baby hamster kidney (BHK) cells, purified to homogeneity, and sequenced; the amino acid sequence was identical to that predicted from liver cDNA. The cloned hGHBP competed in a dose-dependent fashion for binding of 125I-labeled 22-kilodalton (kDa) hGH, and at higher concentrations for binding of 125I-labeled 20-kDa hGH, to IM-9 lymphocytes. hGHBP decreased the association rate of [125I]hGH to the cells without decreasing the dissociation rate. hGHBP blocked the down-regulation of GH receptor in IM-9 cells by both 22- and 20-kDa hGH. hGHBP also blocked the binding of [125I]hGH to PRL receptors on Nb2 lymphoma cells and the effect of the hormone on thymidine incorporation. Binding of both 22- and 20-kDa hGH to the binding protein was demonstrated directly by immunoprecipitation with monoclonal antibody 263. The present work thus establishes the identity of the IM-9 human GHBP from those of liver and placenta, and demonstrates its ability to bind both 22- and 20-kDa hGH with good affinity and to block their biological actions mediated though both somatogenic and lactogenic receptors. The modulation of receptor down-regulation by the BP may be a relevant facet of its physiological role.

Amino Acid Sequence↗
PubMed1989

Child mortality related to seroconversion or lack of seroconversion after measles vaccination.

When blood samples were analyzed for seroconversion after measles vaccination, it was discovered that the vaccine had been ineffective for a certain period. During the 2 years between vaccination and the time of seroanalysis, nonseroconverters had a significantly higher mortality than seroconverters (P less than 0.05). The incidence of measles among nonseroconverters was 30% during the period. Between 9 months and 3 years of age, cumulative mortality was 15.1% for nonseroconverters and 4.5% for seroconverters. The difference in mortality was larger when high risk groups (twins, motherless children) were excluded from the analysis (P less than 0.01). The difference in mortality was particularly marked among children vaccinated in the age group 9 to 11 months. This as well as other community studies suggest that measles vaccination reduces child mortality from the age of vaccination by at least 30%.

Antibody Formation↗
PubMed1988

Effect of interleukin-1 on the biosynthesis of proinsulin and insulin in isolated rat pancreatic islets.

Insulin dependent diabetes mellitus (IDDM) is often preceded or associated with lymphocytic infiltration in the islets of Langerhans (insulitis). We recently demonstrated that interleukin-1 (IL-1) produced by activated macrophages exerts a bimodal effect on insulin release and biosynthesis in isolated rat islets. In the present study we have further analysed the effect of recombinant human interleukin-1 beta (rIL-1) on the biosynthesis and conversion of proinsulin 1 and 2 in rat islets. By RP-HPLC-analysis of islets labelled with [3H]leucine we found that exposure to 6 ng/ml of IL-1 for 24 h reduced the insulin biosynthesis to 6.1 +/- 2.7% (n = 4). During the 3 h labelling period the labelled proinsulin content compared to insulin was increased from 9.0 +/- 1.3% (control) to 26.6 +/- 6.4% in the IL-1 exposed islets, and the ratio between labelled insulin 1 to 2 was increased from 2.0 +/- 0.1 to 3.4 +/- 0.4, respectively. Pulse-chase experiments with [3H]leucine and [35S]methionine indicated a more marked reduction in the conversion rate of proinsulin-2 compared to that of proinsulin-1. In conclusion these experiments demonstrate that IL-1 inhibits insulin biosynthesis by preferential attenuation of the rate of conversion of proinsulin 2.

Animals↗
PubMed1987

Interleukin 1 dose-dependently affects the biosynthesis of (pro)insulin in isolated rat islets of Langerhans.

Human crude and recombinant interleukin 1 (IL-1) was found to dose- and time-dependently affect the biosynthesis of (pro)insulin in isolated rat islets of Langerhans. Incubation of rat islets with either 0.5 U/ml or 5 U/ml of crude IL-1 for 1 h had no detectable effect on (pro)insulin biosynthesis. After 24 hours of exposure 0.5 U/ml of crude or 0.6 ng/ml of recombinant IL-1 (beta) increased the (pro)insulin biosynthesis by 42% and 58%, respectively, whereas a 10-fold greater concentration of IL-1 decreased the (pro)insulin biosynthesis by 74% and 89%, respectively. The increase in (pro)insulin biosynthesis was accompanied by an increase in total protein biosynthesis indicating a nonspecific stimulatory action of low IL-1 concentrations. In contrast, high IL-1 concentrations caused a more selective decrease of the (pro) insulin biosynthesis when compared to the total protein biosynthesis. In addition, low IL-1 concentrations were found to increase and high concentrations to decrease the relative levels of pre-proinsulin mRNA suggesting that IL-1 may act both at a pre- and post-translational level of insulin biosynthesis.

Animals↗
PubMed1987

Islet cytotoxicity of interleukin 1. Influence of culture conditions and islet donor characteristics.

We recently demonstrated that the macrophage product interleukin 1 (IL-1) is cytotoxic to isolated pancreatic islets and hypothesized that IL-1 is responsible for beta-cell destruction in insulin-dependent diabetes mellitus (IDDM). We studied whether the variation in IDDM preponderance with age, sex, and genetic background in vivo is reflected in different susceptibility to IL-1 toxicity of islets in vitro. In addition, we studied the effect of preculture conditions that support endocrine islet cell function and decrease nonendocrine passenger-cell survival on the susceptibility of beta-cells to IL-1 because it is unknown whether IL-1 acts directly on beta-cells or via passenger cells. No differences in susceptibility to various doses of IL-1-containing mononuclear cell supernatants were found between islets isolated from newborn or adult rats, male or female rats, or rats of four inbred strains, indicating that age, sex, and genetic background do not influence the susceptibility of the beta-cell to IL-1. Preculture of islets for 1-7 days in normal atmosphere and preculture of islet clusters in 95% O2 to delete passenger cells did not affect IL-1-mediated cytotoxicity, suggesting that IL-1 acts directly on beta-cells. Increasing the glucose concentration (22 mM) in the culture medium, which is known to protect beta-cells against alloxan toxicity, reduced IL-1 toxicity. Five or 25% normal human serum as well as 5% normal rat serum, but not equivalent concentrations of human serum albumin, inhibited IL-1 toxicity, indicating the presence of IL-1 inhibitors, IL-1 antagonists, or beta-cell-protecting factors in normal serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1983

Progabide: a controlled trial in partial epilepsy.

Progabide (SL 76002) was studied in a randomized double-blind crossover trial using 20 outpatients suffering from partial complex seizures. Progabide was added to the concomitant antiepileptic treatment in a fixed dosage schedule. The design included an open therapy control unit. No significant difference was established between the number of partial seizures during treatment with progabide and placebo. A trend was observed for lower seizure frequency of secondary generalized seizures during treatment with progabide. Only mild and transient side effects were observed. There was no difference between the side effects of progabide and placebo.

Anticonvulsants↗
PubMed1982

Promoter-distal region of the tra operon of F-like sex factor R100 in Escherichia coli K-12.

The distal region of the tra (transfer) operon of F-like plasmid R100 was investigated, using small plasmids derived from R100, primarily the plasmid pSM6. The transposon Tn5 (which confers kanamycin resistance) was inserted at different positions into pSM6, and the transposition derivatives were tested for ability to complement defined tra mutants of the F sex factor. Thus, the tra genes traH, G, T, and D were localized on the plasmid R100. A restriction map of pSM6 was constructed, and the locations of the insertions were mapped, using restriction endonuclease digestion of the plasmid DNA and exploiting the fact that several restriction sites are localized in the inverted repeat regions of the transposon. The gene products of the genes traG, S, T, and D were identified by radioactive labeling of proteins synthesized in minicells carrying the various insertion plasmids followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of another transfer gene, traI, was inferred from these data. Another protein, the r2-A protein, was also identified, and its gene was mapped. On the basis of the data, a best-fit physical map of this region of the tra operon of R100 was constructed. The results confirmed that the general order and size of the distal transfer genes is as in the F sex factor, but showed that differences exist with respect to all of the gene products. The significance of these differences are discussed in the light of the genetic and physical homology (Manning et al., J. Bacteriol. 150:76-88) of the transfer regions.

Bacterial Proteins↗
PubMed1980

Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man.

Interactions between analgesics and anti-epileptic drugs may sometimes present a serious clinical problem. The aim of the study was to investigate the influence of usually applied doses of dextropropoxyphene (DPX) on the steady state levels of carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB). Sixteen patients in monotherapy completed the trial, while four patients dropped out. In patients on CBZ serum levels increased (mean appr. 66%) after 6 days on DPX. In three of the patients a further increase was seen after an additional week on DPX. One patient discontinued the DPX intake because of clinical signs of toxicity, but the remainder were clinically unaffected. CBZ-epoxide levels declined simultaneously. For DPH only a doubtful increase was observed after 1-2 weeks on DPX. For PB an average increase of 20% in serum level was noted after 1 week. The protein binding of CBZ and DPH was not affected. It is concluded that patients on CBZ should be treated only with DPX if monitored properly. Patients on DPH or PB should be followed carefully until further evidence has been produced.

Adolescent↗