Search PubMed⌕ Search

Biomedical subjects

H Christensen

Publications and source records attributed to H Christensen.

At least 217 records · Page 12Linked to original sources

Increased mechanical strength of left colon in old rats treated with growth hormone.

The effects of treatment with 2.7 mg biosynthetic human growth hormone (b-hGH; 2.7 mg/kg b.w./day) for 80 days on the biomechanical properties and collagen deposition of the left colon were studied in 27-month-old male rats. The b-hGH-treated rats increased in body weight by 17%, and the wet weight of colon by 31%. The defatted dry weight and the hydroxyproline content of the left colon were increased by 41 and 29%, respectively, compared with controls. The biomechanical analysis showed that the maximum load and stiffness of the left colonic specimens in the b-hGH-treated group were enhanced by 27 and 60%, respectively, and the strain at maximum load was 24% less than in the control group. The maximum 'stress' and stiffness were 40 and 73% higher, respectively, than in the controls. Histological examination demonstrated that the mean crypt heights was 9% higher in the b-hGH-treated rats than in the controls. Consequently, treatment of old rats with b-hGH may increase the strength, collagen deposition and mucosal crypt height of the left colon.

Aging↗

Dose-dependent stimulatory effect of human growth hormone on the strength and collagen deposition of colonic anastomoses in the rat.

The effects of treatment with four different doses of biosynthetic human growth hormone (b-hGH; 0.125 mg kg-1 d-1, 0.5 mg kg-1 d-1, 2.0 mg kg-1 d-1, 8.0 mg kg-1 d-1) on the bursting strength and collagen deposition of rat colonic anastomoses were studied. Rats receiving 2.0 mg and 8.0 mg b-hGH demonstrated increases in the pre- and postoperative body weights, and the bursting strength and hydroxyproline content of the anastomotic segments in these groups were significantly higher than controls on day 4 postoperatively. The serum levels of insulin-like growth factor I (IGF-I) were significantly higher than the controls after four days of preoperative treatment in the groups receiving 2.0 mg and 8.0 mg b-hGH, and postoperatively the IGF-I levels were significantly higher than those of the controls in the groups receiving 0.5 mg, 2.0 mg and 8.0 mg b-hGH per kg. Consequently, positive correlations were found between treatment doses of b-hGH and anastomotic defatted dry weight, hydroxyproline content and bursting strength of colonic anastomoses.

Anastomosis, Surgical↗

Serum amylase levels in gynecologic patients with acute abdominal pain.

Total amylase and salivary (S) type isoamylase were measured in serum from 80 women with acute abdominal pain admitted to the Department of Gynecology. Fifty-seven patients had verified gynecologic diseases, including 21 patients with inflammation of the internal genitals and 11 with ectopic pregnancy. Twelve patients had an intrauterine pregnancy in the first trimester. None of the 80 patients showed hyperamylasemia.

Abdominal Pain↗

The ontogeny of the uptake systems for glycine, GABA and glutamate in synaptic vesicles isolated from rat spinal cord-medulla.

Synaptic vesicles have been isolated from rat spinal cord-medulla at different postnatal ages, and the ontogeny of the uptake of glycine, gamma-aminobutyric acid (GABA) and glutamate has been investigated. The accumulation of the 3 amino acids increased with increasing time after birth reaching adult level at about postnatal day 30. This developmental increase probably parallels the synaptogenesis and suggests a functional role of the uptake of the amino acids into synaptic vesicles in the nerve terminals. The developmental time course for these vesicular uptake systems was totally different from those of the corresponding plasma membrane uptakes.

Aging↗

Uptake of glycine, GABA and glutamate by synaptic vesicles isolated from different regions of rat CNS.

Synaptic vesicle fractions have been isolated from cerebral cortex, subcortical telencephalon, whole brain and spinal cord by density gradient centrifugation. The Mg2+ ATP-dependent vesicular uptake and the Na(+)-dependent synaptosomal uptake of glycine, GABA and L-glutamate has been compared in the different regions. All these regions contain GABA as inhibitory neurotransmitter, whereas glycine only plays a dominant role as such in the spinal cord. The ratio between GABA and glycine uptake in the different vesicle fractions was similar, and the ratios differed greatly from the ratios in the synaptosomal uptake. In contrast, the ratio between glutamate and GABA uptake in vesicles from different regions differed, and these ratios corresponded to the ratios in the synaptosomal uptake. These results indicate that glycine is taken up into synaptic vesicles from non-glycine terminals, and we suggest that GABA and glycine can be taken up into the same vesicle population.

Adenosine Triphosphate↗

Inhibition of gamma-aminobutyrate and glycine uptake into synaptic vesicles.

The substrate specificity of vesicular GABA and glycine uptake was studied in vesicle fractions from brain and spinal cord, respectively. Glycine, beta-alanine and gamma-vinyl-GABA were competitive inhibitors of the GABA uptake were competitive inhibitors of the GABA uptake by synaptic vesicles in brain. Likewise GABA and beta-alanine turned out to be competitive inhibitors of vesicular uptake of glycine in spinal cord. The apparent K1 values were in the same range as the respective Km values for the transport systems. Accumulation of different amino acids were examined, and the structurally related amino acids GABA, beta-alanine and glycine were all taken up by both vesicle fractions. In the present study, we suggest that there are similarities in the vesicular transporters for GABA and glycine, and the two amino acids are probably taken up into the same vesicle population. The key factor in differentiating between GABA and glycine as transmitters in the terminals could be the synthesis and the high-affinity synaptosomal uptake.

Alanine↗

Molten globule intermediates and protein folding.

The background to the concept of the term "molten globule" as a description of intermediates observed in the folding of globular proteins is discussed. These compact intermediates are characterised by certain properties including the presence of secondary structure and considerable conformational mobility compared to the native, functional state. Those intermediates that are thermodynamically stable under mild denaturing conditions have many features in common with the transient intermediates that accumulate significantly during the process of folding. Attention is drawn to cases where the two types are however distinguished on grounds of their Stokes radius, in which cases there is currently no direct evidence for the involvement of the stable intermediates on the folding pathway. Experimental evidence relating to the early stages in folding is reviewed and compared, highlighting the temporal relationship between general collapse of the polypeptide chain and the formation of secondary structure. The continued use of the term "molten globule" is recommended where the minimum essential structural criteria for this state are met.

Animals↗

Postoperative biosynthetic human growth hormone increases the strength and collagen deposition of experimental colonic anastomoses.

This study examined the effects of preoperative treatment with 2.0 mg biosynthetic human growth hormone (b-hGH)/kg/day on the bursting strength and collagen deposition of experimental left colonic anastomoses, and of intact colon from sham-operated rats. The anastomotic bursting pressure was 55% higher in the b-hGH treated animals on day 2 (p less than 0.05) and 79% higher on day 4 (NS; p = 0.056), and the bursting wall tension was 65% higher on day 2 (p less than 0.05) and 112% higher on day 4 postoperatively (p less than 0.05), than saline-injected controls. The hydroxyproline content of the anastomotic segment in the b-hGH treated rats increased by 56% on day 4 (p less than 0.005) and by 30% on day 6 postoperatively (p less than 0.05), compared with controls. At 3 cm proximal to the anastomoses the defatted dry weight and hydroxyproline content of the healing colons were increased after 6 days compared with the sham-operated rats. There was, however, no difference between the b-hGH treated rats and the paired controls, indicating that growth hormone is not involved in this process.

Anastomosis, Surgical↗

Explicit and implicit memory in dementia and normal ageing.

In two experiments, young subjects, healthy elderly subjects (spouses), and highly intelligent elderly subjects (elite elderly), were compared with dementia patients in a variety of explicit and implicit memory tasks, to investigate two issues: whether priming in Alzheimer-type dementia is contingent upon the presence of pre-existing representations, and whether intelligence modulates performance in explicit memory tasks in healthy ageing. Dementia patients performed as well as spouses in a homo-phone-spelling task. Moreover, they established new contextual associations when memory was tested by word-stem completion. The hypothesis that priming in dementia is contingent upon pre-existing memory representations was not supported. Spouses, elite elderly, and young subjects did not differ in their ability to recognize correctly recently heard stimuli or to complete word stems. However, recall of lists of words and paired associates was better in both young and elite elderly subjects than in spouses. It is concluded that intellectual capacity rather than chronological age in healthy subjects modulates performance in explicit-memory tasks.

Aged↗

Is age kinder to the initially more able? A study of eminent scientists and academics.

Elderly eminent academics and blue-collar workers were compared with Doctor of Philosophy students and trade apprentices to investigate whether intelligence and memory deteriorate at a slower rate in persons with high ability. The elderly groups showed decline on tests of perceptual-motor speed, visuospatial reasoning, inferential thinking and memory relative to the young subjects. Initial ability determined the level of intellectual performance, such that elderly academics maintained their initial advantage over the elderly blue-collar workers. However, with the exception of the Similarities subtest of the Wechsler Adult Intelligence Scale, the rate of change on tests of memory and intelligence did not differ for the high- and low-ability groups. The hypothesis that high ability is associated with a slower rate of cognitive decline was not supported.

Academies and Institutes↗

Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans.

Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used for measurement of blood flow rates. An automatic portable blood pressure recorder and processor unit was used for measurement of systolic blood pressure, diastolic blood pressure, and heart rate every 15 min. The change from upright to supine position at the beginning of the night period was associated with a 30-40% increase in blood flow rate and a highly significant decrease in mean arterial blood pressure and heart rate (P less than 0.001 for all). Approximately 100 min after the subjects went to sleep an additional blood flow rate increment (mean 56%) and a simultaneous significant decrease in mean arterial blood pressure (P less than 0.001) were observed. The duration of this hyperemic phase was 116 min. A highly significant reduction of the subcutaneous vascular resistance (50%) was demonstrated during the hyperemic blood flow rate phase compared with the surrounding phases (P less than 0.0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.

Adult↗

Bronchodilator and corticosteroid reversibility in ambulatory patients with airways obstruction.

With the aim of characterising subgroups, we analysed reversibility tests from 1,048 patients with airways obstruction (baseline FEV1 less than 60% of predicted normal (%pred), and FEV1 to FVC ratio less than 0.6). Spirometry before and after inhalation of salbutamol 0.3 mg and ipratropium bromide 0.06 mg was performed before and after one week of treatment with prednisone 30 mg daily. The changes in FEV1 after bronchodilators showed unimodal distribution (mean = 7.0 %pred, st.dev. = 6.6 %pred). The responses to corticosteroid were more spread out (mean = 6.3 %pred, st.dev. = 13.8 %pred). The correlation between bronchodilator responses before and after corticosteroid treatment was poor (r = 0.30), although highly significant (p less than 0.000,001). The responses to bronchodilators were virtually independent of the steroid reversibility. The corticosteroid response was inversely related to age (r = -0.20, p less than 0.000,001) and smoking habits (r = -0.17, p less than 0.000,001), and moderately associated with blood eosinophilia (r = 0.34, p less than 0.000,001). The frequency distribution of the bronchodilator responses and the steroid response and combinations of the responses were all unimodal, making any distinction between nosologic subgroups arbitrary. It is clear from the study that criteria other than just response to therapy must be employed for distinction of subgroups among patients with airways obstruction.

Adolescent↗

Site-directed mutagenesis of beta-lactamase I. Single and double mutants of Glu-166 and Lys-73.

Two single mutants and the corresponding double mutant of beta-lactamase I from Bacillus cereus 569/H were constructed and their kinetics investigated. The mutants have Lys-73 replaced by arginine (K73R), or Glu-166 replaced by aspartic acid (E166D), or both (K73R + E166D). All four rate constants in the acyl-enzyme mechanism were determined for the E166D mutant by the methods described by Christensen, Martin & Waley [(1990) Biochem. J. 266, 853-861]. Both the rate constants for acylation and deacylation for the hydrolysis of benzylpenicillin were decreased about 2000-fold in this mutant. In the K73R mutant, and in the double mutant, the rate constants for acylation were decreased about 100-fold and 10,000-fold respectively. All three mutants also had lowered values for the rate constants for the formation and dissociation of the non-covalent enzyme-substrate complex. The specificities of the mutants did not differ greatly from those of wild-type beta-lactamase, but the hydrolysis of cephalosporin C by the K73R mutant gave 'burst' kinetics.

Bacillus cereus↗

[Benzodiazepines in blood samples with 0 alcohol content sent to the Institute of Forensic Chemistry].

The Institute of Forensic Chemistry, Copenhagen, receives approximately 29,000 blood samples annually for alcohol determination from drivers suspected of drinking and driving. The incidence of benzodiazepines were estimated in the 877 alcohol-negative samples from six months (01.01-07.31 1983). Eight samples had to be excluded because of insufficient material. Screening for benzodiazepines was made by means of a radioreceptor-method. Quantification and identification of the benzodiazepines was performed by gas- and liquid-chromatography. 15% of the samples were found to be positive for benzodiazepines (13% positive for diazepam and desmethyldiazepam), while an earlier investigation of the same type of material, but including all blood samples, both alcohol-positive and negative showed only 5.8% of the samples positive for benzodiazepines (5.5% positive for diazepam). These findings are in agreement with the results of other investigations. 59% of the diazepam cases had a total concentration of diazepam and desmethyldiazepam higher than 1 mumol/kg. 69% were men and 31% were women. Most cases were found in the age group 20-30 years old. In only 22% of the cases, had the police required analyses for benzodiazepines. Due to the known difficulties in instituting proceedings against drivers influenced by drugs, it is feared, that the drug problem in connection with driving will be forgotten, all the while it is increasing steadily.

Automobile Driving↗

Beta-lactamases as fully efficient enzymes. Determination of all the rate constants in the acyl-enzyme mechanism.

The rate constants for both acylation and deacylation of beta-lactamase PC1 from Staphylococcus aureus and the RTEM beta-lactamase from Escherichia coli were determined by the acid-quench method [Martin & Waley (1988) Biochem. J. 254, 923-925] with several good substrates, and, for a wider range of substrates, of beta-lactamase I from Bacillus cereus. The values of the acylation and deacylation rate constants for benzylpenicillin were approximately the same (i.e. differing by no more than 2-fold) for each enzyme. The variation of kcat./Km for benzylpenicillin with the viscosity of the medium was used to obtain values for all four rate constants in the acyl-enzyme mechanism for all three enzymes. The reaction is partly diffusion-controlled, and the rate constant for the dissociation of the enzyme-substrate complex has approximately the same value as the rate constants for acylation and deacylation. Thus all three first-order rate constants have comparable values. Here there is no single rate-determining step for beta-lactamase action. This is taken to be a sign of a fully efficient enzyme.

Acylation↗

Growth hormone increases the bursting strength of colonic anastomoses. An experimental study in the rat.

The effect of growth hormone on the bursting strength of left colonic anastomoses was investigated experimentally. Seventy-two 3 month-old female rats were randomized into two groups receiving daily injection of either saline (controls) or 2.0 mg biosynthetic human growth hormone per kg body weight per day. All injections were started 7 days before a left colonic resection and anastomosis, and continued until sacrifice at the 2nd, 4th or 6th post-operative day. The bursting strength of the anastomoses was tested in anaesthetized, living rats. The bursting pressure and the bursting wall tension of the growth hormone treated animals were increased two-fold on the second post-operative day (2p less than 0.005) and three-fold on the fourth post-operative day (2p less than 0.05), compared with controls. There was no difference in the bursting pressure or the bursting wall tension on the sixth postoperative day. The mass of the resected segment was increased by the pre-operative growth hormone treatment, whereas the hydroxyproline content was unchanged. In conclusion, treatment with biosynthetic human growth hormone increases the strength of colonic anastomoses in the early phases of healing.

Anastomosis, Surgical↗

Double labelling of cell surface antigens with colloidal gold markers.

Particles of colloidal gold of different diameters (15 nm and 40) have been used to distinctively label different surface antigens expressed on the surface of human peripheral blood B and T lymphocytes. Silver enhancement has been used to facilitate the observation of the gold particles. Observations were carried out in the backscattered electron imaging mode of the scanning electron microscope. Two different methods have been compared: in Method I the two antigens have been identified by monoclonal antibodies of different classes (IgG and IgM); in Method II monoclonal antibodies of the same subclass were used but the ligands were different (goat anti-murine Ig versus biotin/streptavidin). Some cross-reactivity was observed with Method I, but not with Method II.

Animals↗