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Biomedical subjects

H Andersen

Publications and source records attributed to H Andersen.

At least 55 records · Page 3Linked to original sources

Motor pathway function in normoalbuminuric IDDM patients.

Central motor pathways were studied in 17 normoalbuminuric insulin-dependent diabetic (IDDM) patients who had been diabetic for more than 20 years, and compared with findings in 17 age-, sex-, and height-matched control subjects. The central motor conduction time was calculated from recordings of the compound muscle action potentials of the abductor pollicis brevis muscle after single transcranial and spinal root magnetic stimulation. The central motor conduction time from motor cortex to cervical spinal roots was 9.8 +/- 1.65 ms in diabetic patients and 10.1 +/- 1.48 ms in control subjects. In diabetic patients with neuropathy the central motor conduction time was 9.5 +/- 1.76 ms vs 10.1 +/- 1.56 ms in patients without neuropathy. The excitability of the motor pathways was studied by paired transcranial magnetic stimulation at interstimulation intervals of 30-1000 ms. In normal control subjects, an early facilitation of the amplitude of the compound muscle action potential at an interstimulation interval of 30 ms was found, while no facilitation was present in diabetic patients. In addition the compound muscle action potential latencies were prolonged at interstimulation intervals of 30-50 ms in diabetic patients. The changes of excitability did not correlate with the presence of peripheral neuropathy, metabolic control or diabetes duration. It is concluded that long-term normoalbuminuric IDDM patients have imparied excitability but normal central conduction time of the motor pathways.

Adult↗

Bovine histidine-rich glycoprotein is a substrate for bovine plasma factor XIIIa.

Histidine-rich glycoprotein was purified from bovine plasma and the identity of the protein confirmed through amino acid sequencing. Activated bovine factor XIIIa catalyzed the incorporation of 1 nmol of 1,4-[14C]putrescine into 1 nmol of bovine histidine-rich glycoprotein, showing that histidine-rich glycoprotein has the ability to participate in transglutaminase-catalyzed reactions in vivo.

Amino Acid Sequence↗

Inability of insulin to maintain normal nerve function during high-frequency stimulation in diabetic rat tail nerves.

The effect of insulin on the response to long-term high-frequency stimulation (HFS = 143 Hz for 20 min) was studied in mixed tail nerves of acute streptozotocin-induced diabetic rats. In consecutive tests, untreated diabetic rats showed a significant decrease in nerve conduction velocity (NCV) and peak-to-peak amplitude (P-Pamp) and the depression of the P-Pamp during HFS was augmented. In contrast, NCV and P-Pamp in the insulin-treated rats were unchanged from the prediabetic state, but the depression of the P-Pamp during HFS reached the same degree as in untreated rats. This implies that although insulin treatment of acute experimental diabetes is able to preserve a normal NCV and P-Pamp in the resting state, it is unable to preserve normal nerve function under stress produced by HFS. Monitoring of the axon membrane functional capacity may have clinical implications in the control of peripheral neuropathies.

Action Potentials↗

Long term impact of high titer Edmonston-Zagreb measles vaccine on T lymphocyte subsets.

Several trials of high titer measles vaccine (> 10(4.7) plaque-forming unit) have found female recipients of Edmonston-Zagreb (EZ) vaccine to have lower survival than female recipients of standard measles vaccine. Two trials with medium and high titer EZ vaccine from the age of 4 months were conducted in Guinea-Bissau. To test for possible long term impact on the immune system, an investigation of T cell subsets was conducted among all children still residing in the community at 3 to 5 years of age. No differences were found between recipients of medium titer vaccine and controls. In the second trial, however, recipients of high titer had lower CD4:CD8 ratios than controls and had significantly higher CD8 percentages and lower CD4:CD8 ratios than recipients of medium titer EZ. When analyzed by sex, differences were found only among the girls. However, these differences were small and seemed unlikely to explain the reduced survival which has been associated with high titer EZ measles vaccination. In the 2 years after the investigation of T cell subsets, there was no increased mortality for recipients of EZ vaccine. Hence it is unlikely that high titer vaccine has an persistent adverse effect on survival after 3 years of age.

CD4-CD8 Ratio↗

Reduced capability of transmitting high frequency impulses in tail nerves of diabetic rats.

The effect of long-term (40 min) high frequency stimulation (143 Hz) of sensory-motor tail nerves was studied in normal and in streptozotocin-diabetic rats. The study comprised a 6-week period, repeating the test at 2-week intervals. In the initial (prediabetic) study, single experiments showed a mild depression of the peak-to-peak amplitude during high frequency stimulation, which reversed completely during a subsequent rest period. In normal rats, the amplitude depression was unchanged in repeated tests over a 6-week period. Diabetic rats showed a greater amplitude depression during high frequency stimulation. The difference was statistically significant after 2 weeks, but showed no further change at subsequent tests. The greater decrease in the amplitude in diabetic rats may reflect a depression of the axon membrane function, which may be the functional correlate to the inhibition of the Na/K ATPase activity in diabetes, described by others. Monitoring of the axon membrane functional capacity may have clinical implications in the control of peripheral neuropathies.

Action Potentials↗

Papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane in isolated frog skin.

The effect of papaverine, an inhibitor of the phosphodiesterase responsible for breakdown of cAMP, on the transepithelial sodium transport across the isolated frog skin was investigated. Serosal addition of papaverine caused initially an increase in the short-circuit current (SCC), a doubling of the cellular cAMP content and a depolarization of the intracellular potential under SCC conditions (Vscc). The initial increase in the SCC was followed by a pronounced decrease both in the SCC and in the natriferic action of antidiuretic hormone (ADH), but papaverine had no inhibitory effect on the ability of ADH to increase the cellular cAMP content. As SCC declines, no hyperpolarization was observed. The I/V relationship across the apical membrane during the inhibitory phase, revealed that papaverine reduces the sodium permeability of the apical membrane (PNaa) as well as intracellular sodium concentration. These observations and the previously noted effect of papaverine on Vscc indicates that papaverine must have an effect on the cellular Cl or K permeability. The basolateral Na,K,2Cl cotransporter was blocked with bumetanide, which should bring the cellular chloride in equilibrium. Bumetanide had no effect on basal SCC and Vscc. When papaverine was added to skins preincubated with bumetanide, the effect of papaverine on SCC and Vscc was unchanged. Therefore, the depolarization of Vscc, observed during the papaverine-induced inhibition of the SCC, must be due to a reduction in the cellular K permeability. In conclusion, it is suggested that papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane of the frog skin epithelium.

Animals↗

Increased yield of myeloid progenitor cells in bone marrow harvested for autologous transplantation by pretreatment with recombinant human granulocyte-colony stimulating factor.

Pretreatment with haemopoietic cytokines prior to marrow harvest may result in improved quality of bone marrow harvested for autologous bone marrow transplantation (BMT). Such improvements may reduce the risk for graft failure and decrease time to engraftment. Patients undergoing autologous BMT received recombinant human G-CSF (rhG-CSF) immediately prior to marrow harvest. rhG-CSF was administered as daily subcutaneous injections for 5 days at 5 micrograms/kg body weight. Comparison of bone marrow samples before and after rhG-CSF treatment showed an increased bone marrow cellularity and a ninefold increase in the number of marrow leucocytes per volume aspirated. The mean marrow myeloid:erythroid ratio increased from 2.6 to 4.0. The mean numbers of immature (CD38 positive) and proliferating (CD71 positive) myeloid cells increased significantly from 41.6 to 50.8% and from 17.0 to 34.8%, respectively. Other subsets studied, including CD34 positive stem cells, were unchanged. The relative numbers of day 7 and 14 granulocyte-macrophage colony-forming units (day 7/14 GM-CFU) were unchanged. Long-term marrow cultures revealed that the numbers of 'long-term culture initiating cells' were unchanged after rhG-CSF treatment in spite of the ninefold increase in cellularity. To date, five of the patients have been transplanted with autologous marrow harvested after rhG-CSF treatment. Time to trilineage engraftment was unchanged compared with historical controls. We conclude that pretreatment with rhG-CSF prior to marrow harvest may improve the graft by increasing the total number of myeloid lineage restricted progenitor cells, resulting in stable but not accelerated myeloid engraftment of autologous marrow.

Bone Marrow Transplantation↗

Effect of 12-O-tetradecanoyl phorbol 13-acetate on solute transport and production of cAMP in isolated frog skin.

In the present study we have examined the action of the phorbol diester tetradecanoyl phorbol acetate, an activator of protein kinase C, on the transepithelial transport of sodium, chloride and water and the production of cAMP in the isolated frog skin epithelium (Rana esculenta). Addition of tetradecanoyl phorbol acetate to the mucosal solution resulted initially in an increase in the short-circuit current, which was followed by a progressive decrease. If the short-circuit current was first activated by addition of the antidiuretic hormone, arginine vasotocin, then the addition of tetradecanoyl phorbol acetate resulted only in a pronounced inhibition. The changes in the short-circuit current were the result of changes in the active influx of Na+. The effect of tetradecanoyl phorbol acetate on the intracellular potential measured under short-circuited conditions (Vscc) was time-dependent. Just after addition of tetradecanoyl phorbol acetate to the mucosal solution, Vscc depolarized; this was followed by a slight hyperpolarization, after which Vscc continued to decline. The inhibition of the Na+ transport by tetradecanoyl phorbol acetate was associated with a decline in the response to the antidiuretic hormone (arginine vasotocin), but the ability of arginine vasotocin to increase the cellular level of cAMP and to stimulate the osmotic water flow was not affected by the presence of tetradecanoyl phorbol acetate. In skin halves in which the short-circuit current was stimulated with arginine vasotocin, addition of tetradecanoyl phorbol acetate resulted in a dose-dependent inhibition of the short-circuit current, but only minor changes in Vscc were observed. The results presented suggest that the addition of tetradecanoyl phorbol acetate to the isolated frog skin first increases and then decreases the arginine vasotocin-sensitive sodium permeability of the apical membrane. This might be due to a stimulating effect of tetradecanoyl phorbol acetate on both the activation and deactivation (turnover) of the sodium channels.

Animals↗

Low molecular weight heparin Novo (LHN-1) does not cross the placenta during the second trimester of pregnancy.

Unfractionated heparin (UF-H) has been the drug of choice for the treatment of thromboembolic disorders during pregnancy. Low molecular weight heparin (LMW-H) preparations may present some advantages over UF-H. They have longer half-lives and a better bioavailability after subcutaneous (s. c.) injection and may cause less bleeding. It has not yet been established whether LMW-H Novo (LHN-1) crosses the placenta. 17 women admitted for abortion during the second trimester of pregnancy (induced by application of prostaglandine PGE2 gel at a concentration of 0.25 mg/ml into the cervix) were given s. c. 35 anti-Xa units per kg of body weight of LHN-1 (Novo). 10 patients not receiving LHN-1 and their fetuses served as a control group. 7 women in whom the time interval between injection of LHN-1 and expulsion of the fetus was less than 3 h or more than 7 h were excluded from further study. In one fetus blood collection failed. Anti-Xa and anti-IIa levels increased approximately ten-fold in women receiving LHN-1 [anti-Xa units/ml from 0.02 +/- 0.01 (mean +/- SD) to 0.17 +/- 0.01, p less than 0.001; anti-Ha units/ml from less than 0.01 +/- 0.01 to 0.07 +/- 0.03], but remained below the detection limit in their fetuses as well as in the women and fetuses of the control group. We conclude that LHN-1 at these doses does not cross the placenta during the second trimester of pregnancy to suggest that LHN-1 may be a safe alternative to heparin in the management of the thromboembolic complications during pregnancy.

Abortion, Induced↗

The bimodal effect of interleukin 1 on rat pancreatic beta-cells--stimulation followed by inhibition--depends upon dose, duration of exposure, and ambient glucose concentration.

To investigate the hypothesis that interleukin 1 initially stimulates and then suppresses beta-cell function and that this sequential effect is directly related to interleukin 1 dose, duration of exposure, and ambient glucose concentration, insulin release was measured from cultured newborn rat islets exposed for 6 h to 6 days to interleukin 1 at doses ranging from 20 to 2000 ng/l at glucose concentrations of 3.3, 5.5 and 11 mmol/l. After 6 h of exposure and at all three glucose levels, all doses of interleukin 1 stimulated insulin release, maximal stimulation (370% of control) being observed at 5.5 mmol/l glucose and 100 ng/l interleukin 1. In contrast, after 6 days, all doses of interleukin 1 were inhibitory irrespective of glucose level, maximal inhibition (90%) being observed at 11 mmol/l glucose and 2000 ng/l interleukin 1. At 24 and 48 h of exposure, the biphasic effect of interleukin 1 was observed: lower doses of interleukin 1 at lower glucose concentrations at 24 h being more stimulatory with transition to inhibition directly related to higher glucose levels, higher interleukin 1 doses, and longer exposure. After 48 h, 200 ng/l of interleukin 1 increased insulin release to 220% at 3.3 mmol/l glucose, but at 11 mmol/l glucose a 60% suppression was seen. On the basis of these data we suggest that interleukin 1's effect on beta-cells is bimodal: stimulation followed by inhibition. Increasing interleukin 1 dose and ambient glucose concentration shift this response to the left. Experimental results will, and in vivo effects may, depend upon these three variables.

Animals↗

Structure and accessibility of domain I of Escherichia coli 23 S RNA in free RNA, in the L24-RNA complex and in 50 S subunits. Implications for ribosomal assembly.

Domain I of 23 S RNA of Escherichia coli was probed in renatured RNA, in the protein L24-RNA complex and in 50 S subunits with ribonucleases specific for single- and double-stranded regions and with chemical reagents specific for guanosines (N-1 and N-2), adenosines (N-1, N-7 and N-6), cytidines (N-3) and uridines (N-3). Reactive sites were detected by a reverse transcriptase procedure. The results support most new features of the latest version of the Santa Cruz/Urbana model of the secondary structure, which is based on evidence from sequence comparison. Most double-helical segments were reactive to cobra venom ribonuclease to some degree; the exceptions were the five "long-range" helices that are probably compactly folded within the structure. The data provide evidence for the occurrence of A(syn) X G(anti) pairings in internal loops and at the ends of some helices; they also support the existence of extensive higher-order structuring, especially within the interhelical regions, and are compatible with two of three tertiary interactions in the free RNA that were predicted from comparative sequence studies. Protein L24 is the only primary binding protein that associates with domain I and it strongly protects two sites against ribonuclease and chemical activity. Site A has the properties of a classic protein binding site and we conclude from four lines of evidence that it is the primary attachment site. Site B is rich in highly conserved, unpaired adenosine residues and lies in a potentially critical region of the structure adjoining a group of long-range helices; we infer that L24 binding here is related to the important role of L24 in initiating ribosomal assembly; the existence of both sites is supported, independently, by genetic experiments. L24-induced enhanced reactivities were detected throughout the domain and are consistent with a general "tuning" of the RNA structure. The RNA domain in the 50 S subunits is almost completely resistant to ribonucleases and only a few sites, mainly interhelical, are accessible to chemical reagents. The appearance of several newly reactive nucleotides in the subunit RNA and the enhancement of some others suggest that some minor conformational changes occur on assembly. Nevertheless, the minimal secondary structure of the renatured RNA appears to be retained. We draw the general conclusion that domain I is a highly structured domain that is important for initiating assembly and for the subsequent organization of the ribosome.

Binding Sites↗