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Biomedical subjects

O Henriksen

Publications and source records attributed to O Henriksen.

At least 235 records · Page 13Linked to original sources

Evaluation of a method for determination of mean transit time of xenon-133 in the lungs.

The purpose of the study was to determine the mean transit time, t, for Xe-133 in the lungs and to compare the results with t for helium determined simultaneously by the helium-dilution technique. Thirteen normal subjects were studied, and four patients with pulmonary disease. No significant difference was observed between the mean transit times for Xe-133 and helium obtained in normal subjects during equilibrium as well as during desaturation. The mean washout time for Xe-133 during desaturation, rho a/h (calculated as the area under the desaturation curve divided by activity at equilibrium), was significantly longer than the mean transit time for He. Similar results were obtained in the patients. Thus it is possible to determine total ventilation per unit volume correctly when the initial washout rate is used, whereas calculations based on rho a/h underestimate V/V. Accordingly, rho a/h should not be used as equivalent to the mean transit time. However, rho a/h might give information of clinical value, especially in patients with chronic obstructive pulmonary disease.

Adult↗

Purification and chemical characterization of papain-solubilized histocompatibility-2 antigens from mouse liver.

A large scale purification of histocompatibility-2 (H-2) antigens from mouse liver is described. The antigens were solubilized by a limited papain digestion of a crude preparation of liver membranes (strain A/J) and purified by ion exchange chromatography, gel filtration, affinity chromatography, and isoelectric focusing. The overall degree of purification of H-2Kk was 1,300-fold and that of H-2Dd was 1,500-fold; approximately 8 mg of purified H-2a antigens were obtained from 1 kg of liver. The purification was followed by a sensitive radioimmunoassay in which H-2a-containing fractions were used to inhibit the binding of 125I-labeled H-2a to appropriate antisera. H-2Dd and H-2Kk co-purified through all the steps but the concentration of H-2Kk was 2- to 3-fold higher than that of H-2Dd in the liver homogenate as well as in the purified H-2 preparation. beta 2-microglobulin was initially present in a 3- to 10-fold excess over H-2 in the liver homogenate, but the purified H-2 preparation contained approximately 2 mol of alloantigenic heavy chain/mol of beta 2-microglobulin. Isoelectric focusing and disc-gel electrophoresis showed a charge heterogeneity of H-2, with a mean isoelectric point of pH 4.9. Electrophoresis on sodium dodecyl sulfate gels showed one band. Denaturing conditions were required to remove beta 2-microglobulin and small amounts of impurities from H-2. The amino acid sequence of the first 27 residues of the isolated heavy chains was determined.

Amino Acid Sequence↗

Distensibiltiy of the papaverine-induced passive vascular bed in dermis of generalized scleroderma.

Passive distensibility of of the vascular bed in cutaneous tissue of the hand was examined in 7 normal persons and 15 patients suffering from generalized scleroderma of the acrosclerosis type. Paralysis of vascular smooth muscle cells was obtained by locally injected papaverine. Increase in vascular transmural pressure was induced by lowering the limb. Blood flow was estimated by the local Xenon wash-out technique. There was no significant difference between the patients and the normals in relative blood flow during lowering, when injection volumes of 0.005 and 0.02 ml were used, indicating that distensibility of the vascular bed in cutaneous tissue in generalized scleroderma is not diminished. However, in generalized scleroderma an injection volume of 0.1 ml caused a significant decrease in relative blood flow during lowering. This phenomenon observed in the patients probably reflects changes in total tissue pressure opposing distension of the vascular bed. This suggests an altered pressure-volume relationship of the interstitial fluid spaces in cutaneous tissue of generalized scleroderma.

Adult↗

Comparative steady state serum levels of valproic acid administered as two different formulations--Deprakine and Orfiril.

Plain tablets of sodium valproate (VPA), a useful antiepileptic drug, are bitter tasting and produce gastric irritation which leads to poor patient compliance. We have studied the steady state serum levels of VPA which can be produced in epileptic patients before and after a 1 week treatment with a plain tablet (Deprakine) versus an enteric coated tablet (Orfiril). The latter drug produced in most patients a higher drug fasting blood level than the uncoated preparation (22%). The enteric coated tablets appeared also better tolerated.

Absorption↗

'Distensibility' of the papaverine-relaxed vascular bed in human subcutaneous tissue.

The effect of an increase in vascular transmural pressure upon the blood flow in two subcutaneous vascular beds, maximally dilated by papaverine was studied in 6 healthy humans. Blood flow was measured on the dorsum of the hand and at the lateral malleolus by the local 133Xe washout technique. Increase in vascular transmural pressure was induced by lowering the labelled area various distances below heart level. Lowering the area caused an increase in blood flow. The increase was less pronounced in the legs than in the hand. As arterial perfusion pressure head remained constant during lowering, this indicates that the relative decrease in vascular resistance was smaller in the leg than in the hand. Experimental edema did not influence the relative decrease in vascular resistance. The results suggest that 'distensibility' of the resistance vessels is smaller in the leg than in the hand. This might be due to a structural adaptation of the vascular wall in vessels often subjected to increased hydrostatic pressure.

Blood Pressure↗

Decreased blood flow in a papaverine-induced passive vascular bed in sclerodermal skin.

Blood flow was measured in the form of 133Xenon washout rate constants in a cutaneous vascular bed made passive by intracutaneous injection of a 133Xenon-papaverine mixture. Experiments were performed using injection volumes of 0.005, 0.02, 0.1 and 0.2 ml in 7 normals and 15 patients suffering from generalized scleroderma. Blood flow was closely related to the volume of fluid injected, probably reflecting dilution of tissues and increased diffusion distances when injection volumes were increased. When using injection volumes of 0.005 and 0.02 ml, blood flow was significantly reduced in the patients, as compared with normals, probably because of a decreased capillary density in cutaneous tissue in generalized scleroderma.

Adult↗

Differences in the capacity of simian virus 40 (SV40) tumor antigens on cells, membranes and in soluble form to induce transplantation immunity in hamsters and mice.

The immunogenicity of the SV40 tumor-specific transplantation antigen (TSTA) on cells, cell particulates and solubilized membranes was studied in mice and in Syrian hamsters. Immunizations were done with various concentrations of tissue-culture-passaged, non-virus-releasing transformed cells, purified cell membranes and in some cases purified nuclei and papain-solubilized membranes obtained from several species, including the mouse, hamster, man, and sheep. All transformed cell lines were T-antigen-positive. The immunosensitive mKSA line of BALB/c mice and the immunosensitive SV34 cell line of the hamster were used for tumor challenge. All materials, regardless of source and of type of preparation, were strikingly immunogenic in the mouse but only SV40 virus and SV34 (hamster) cells provided protection against tumor cell challenge in the hamster. Also, in a limited study, BKV-transformed hamster cells and purified cell membranes and JCV-transformed hamster cells were found to be immunogenic by the tumor rejection assay in the mouse but not in the hamster. SV40 immunization did not protect the hamster against BKV- and JCV-transformed hamster cells. These results are discussed in terms of possible different specificities resident on the TSTA molecule.

Animals↗

Structural characterization of H-2 antigens purified from mouse liver.

Papain solubilized H-2a histocompatibility antigens (H-2Kk plus H-2Dd) have been purified by a large-scale procedure that can routinely provide 2-3 mg of heavy chain from 1 kg of mouse liver. The heavy chains were homogeneous by sodium dodecyl sulfate electrophoresis. Disc gel electrophoresis resolved two protein bands that were identified as H-2Dd and H-2Kd by immune complex formation and autoradiography. Comparative amino acid composition and NH2-terminal sequence analyses of unfractionated H-2a, H-2Kk, and HLA suggested close structural relationships. However, the following observations suggest that papain cleaves these membrane bound antigens at different positions with respect to the COOH terminus: the molecular weight of the peptide portion of papain solubilized HLA is smaller than that of H-2 (30,000 versus 33,700); the COOH-terminal sequences are different; and, finally, papain-solubilized H-2 contains a free cysteine residue in addition to the two disulfide bridges that are present in both H-2 and HLA.

Amino Acid Sequence↗

Distensibility of the vascular bed in subcutaneous tissue in generalized scleroderma.

Passive distensibility of resistance vessels in subcutaneous tissue of hand and leg was examined in 6 normals and 8 patients suffering from generalized scleroderma of the acrosclerosis type. Local paralysis of smooth muscle was obtained by injection of papaverine and increase in transmural pressure by lowering the limb. Blood flow was estimated by the local 133Xenon wash-out method. Distensibility of blood vessels in subcutaneous tissue in generalized scleroderma was not decreased to a significant degree, whereas, both in patients and normals, the blood vessels of the leg exhibited diminished distensibility compared to blood vessels of the hand. The findings suggest that the morphologic changes of vascular and extravascular tissue observed in sclerodermic skin do not affect distensibility of the vascular bed in subcutaneous tissue.

Adult↗

Dose-dependent effect of topical corticosteroids on blood flow in human cutaneous tissue.

In seven healthy subjects the dorsum of the hand was treated with beta-methasone valerate cream in increasing concentrations, from 0.1 to 1.0%, and with hydrocortisone butyrate 0.1% with or without plastic occlusion. Under conditions of controlled room temperature, blood flow in treated, placebo-treated, and untreated cutaneous tissue was measured using the local 133Xenon wash-out technique. Placebo creams did not affect cutaneous blood flow, but beta-methasone valerate 0.1% reduced blood flow and 1.0% increased it. An increase in blood flow was also observed after use of hydrocortisone butyrate under plastic occlusion. The results indicate a dual effect of potent corticosteroids on cutaneous blood flow.

Administration, Topical↗

Quantitative in vivo studies of soluble simian virus 40 tumor-specific transplantation antigens of the mouse.

Quantitative studies have been performed on the immunogenicity of a membrane-bound antigen of a simian virus 40 (SV40) -induced sarcoma in syngeneic BALB/c mice and of subcellular fractions derived from this tumor. The objectives of the investigation were: a) to develop a quantitative in vivo assay of the tumor-specific transplantation antigen (TSTA) and b) to compare the distribution of histocompatibility antigens, H-2, with that of the SV40 TSTA during several fractionation steps. The immunogenicity of the TSTA-containing fractions was assessed from dose-response curves relating tumor size and the amount of protein used for immunization. After digestion of the tumor cell membranes with a limited amount of papain, H-2 as well as TSTA were present in a soluble form. A single immunization with only 2 microng of the solubilized TSTA reduced the tumor size by 70% compared to that in nonimmunized control animals. The results of several fractionation steps suggest that H-2 and the TSTA are not tightly associated in the solubilized immunogenic material.

Animals↗

Local regulation of blood flow in subcutaneous tissue in generalized scleroderma.

The effect of orthostatic changes in vascular transmural pressure on blood flow in subcutaneous tissue was studied in 10 patients with the acrosclerotic type of generalized scleroderma. Blood flow was measured on the back of the hand by the local 133xenon washout technique. The blood flow remained constant when the hand was elevated 20 cm above the jugular notch, indicating that there is autoregulation of blood flow, When the hand was lowered 40 cm below by 50% observed in normals. Thus, intrinsic vascular reactions responsible for the autoregulator response are present, whereas the normal "vasoconstrictor response" to an increase in venous transmural pressure is almost abolished in tissues with sclerodermic changes. The abolition of the vasoconstrictor response is probably due to sympathetic neuropathy associated with the sclerodermic changes.

Aged↗

Effect of "vein pump" activation upon venous pressure and blood flow in human subcutaneous tissue.

The effect of "vein pump" activation upon superficial venous pressure and blood flow in human subcutaneous adipose tissue was studied in 6 normals and 2 patients with venous insufficiency. Blood flow in subcltaneous tissue was measured at the lateral malleolus by the local 133Xenon washout technique, with the subject placed in a supine position. During passive lowering of the leg blood flow decreased 50 per cent and total vascular resistance increased 136 per cent. Activation of the vein pump by continuously tipping the foot up and down caused a decrease in venous pressure of 5 mmHg in horizontal position. Venous pressure increased only by 8 mmHg when the leg was lowered during exercise. In this situation blood flow remained constant corresponding to an increase in vascular resistance of 42 per cent. However increasing venous pressure to 28 mmHg by venous stasis in the lowered leg during exercise caused an additional increase in vascular resistance of 82 per cent. In the patients with venous insufficiency exercise did not prevent the decrease in blood flow during lowering of the leg. Hence venous pressure elevation of 25 mmHg or more caused an additional increase in vascular resistance in subcutaneous tissue, "vasoconstrictor response". It is concluded that this "vasoconstrictor response" depends on a vasoconstrictor impulse transmission from veins to arterioles, veno-artertolar reflex.

Adipose Tissue↗

Local reflex in microcirculation in human skeletal muscle.

The effect of venous stasis of 40 mmHg upon blood flow in human skeletal muscle was studied in four normal subjects and in two chronically sympathectomized patients. Blood flow in skeletal muscle was measured by the local 133Xenon washout technique. Blood flow decreased about 30 per cent during venous stasis of 40 mmHg. In a "passive vascular bed" induced by means of histamine, blood flow decreased only by 16 per cent, indicating that the decrease in blood flow is due to a vasoconstrictor response to increase in vascular transmural pressure. The vasoconstrictor response was unaffected by a spinal sympathetic blockade, but was blocked in areas infiltrated with lidocaine or with phentolamine. The vasoconstrictor response was present in the nonoperated limbs used as a control, but abolished in the denervated arms in the two chronically sympathectomized patients. The findings strongly suggest that the vasoconstrictor response in skeletal muscle is due to a local nervous mechanism involving adrenergic fibres. Thus a local reflex mechanism, most likely a sympathetic axon reflex, seems to be present in human skeletal muscle as in cutaneous and subcutaneous tissue. This indicates that about 45 per cent of the change in total vascular conductance, when a person changes from supine to upright position, is due to this local reflex mechanism operating independently of the central nervous system.

Histamine↗