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Biomedical subjects

T Christensen

Publications and source records attributed to T Christensen.

At least 199 records · Page 11Linked to original sources

Diabetic macroangiopathy. Medial calcifications, narrowing, rugosities, stiffness, norepinephrine depletion and reduced blood flow capacity in the leg arteries.

Five quantitative studies performed to disclose and measure diabetic abnormalities in the leg arteries are reported and briefly discussed. A medial as well as an intimal disease was found in the diabetic leg arteries. Thus roentgenological medial calcification correlated to glucose intolerance in older non-diabetics and to diabetes duration in young insulin dependent diabetics. An intimal roughness was disclosed by arteriography in young insulin-dependent diabetic patients. The roughness grew worse the longer the diabetes persisted. The development of this abnormality did not take place simultaneous with the medial calcification, but was closely connected with another disclosed abnormality, a uniform arterial narrowing, quite unlike the well known abrupt narrowing in older patients. The existence of a uniform arterial narrowing in diabetic patients was confirmed by ultrasonography and the use of this technique further revealed arterial stiffness as a long-term diabetic phenomenon. A functional abnormality of the leg arteries of diabetic patients was disclosed by measurement of the postischemic peak blood flow in the leg in a 45 degree feet-down position. A vast destruction of the autonomic nerves of the peripheral arteries was demonstrated by measurement of the norepinephrine content post mortem in long-term diabetic patients. The results reported suggest a specific element in the large-vessel disease of diabetic patients.

Adult↗

Retention and photodynamic effects of haematoporphyrin derivative in cells after prolonged cultivation in the presence of porphyrin.

Photoradiation therapy of cancer in the presence of haematoporphyrin derivative is based on a retention of porphyrin in malignant tissue. After long term incubation of NHIK 3025 cells in the presence of 25 microgram ml-1 haematoporphyrin derivative, one fraction is easily removed from the cells by washing with a serum-rich medium. Another fraction remains bound to the cells for a prolonged time. The former does not contribute to the photosensitivity of the cells while the latter, the tightly-bound component, results in a photosensitivity proportional to the cellular contents of porphyrin. Transformed cells are shown to be slightly more sensitive and to retain 25-50% more haematoporphyrin derivative than non-transformed cells. Cytological effects of light absorbed by the tightly-bound component have been studied. The growth of treated cells is similar to that of control cells after a dose-dependent post irradiation lag period. A relatively slow leakage of lactate dehydrogenase (LDH) out of the cells takes place after treatment. The treatment induces a significant increase in the frequency of sister chromatid exchanges (SCE). We conclude that photoactivation of the tightly-bound fraction of haematoporphyrin derivative induces less damage to the outer cell membrane and probably more intracellular damage than irradiation of cells after a short period in contact with the derivative.

Animals↗

Fatigue and cardiorespiratory function following abdominal surgery.

Subjective feelings of fatigue were assessed before operation and 10, 20 and 30 days after uncomplicated elective abdominal surgery in 16 otherwise healthy patients, using a constructed fatigue scale model. In addition, all patients had an orthostatic stress test performed at the same times. Six of the patients also underwent a bicycle ergometer test measuring heart rate and oxygen consumption. Subjective feelings of fatigue were increased (P less than 0.01) at all three postoperative observations, and only 5 of 16 patients returned to their preoperative level. The increased subjective feeling of fatigue correlated positively (RS = 0.53, P less than 0.001) with the increased pulse rate seen during orthostatic stress after operation. Heart rate was about 5 per cent higher (n.s.) after operation when bicycling at the same work loads, while oxygen consumption decreased by about 2 per cent (P less than 0.01) at all three postoperative bicycle tests. It is concluded that even electric uncomplicated abdominal surgery is followed by a pronounced feeling of fatigue, which may persist 1 month after surgery in about one-third of patients. The fatigue scale model seems applicable for future studies on the pathogenesis and treatment of the postoperative fatigue syndrome.

Abdomen↗

Autogenous control: ribosomal protein L10-L12 complex binds to the leader sequence of its mRNA.

Ribosomal proteins L10 and L12 are encoded in the L10 operon, situated at position 89.5 min on the Escherichia coli genetic map, and are able to regulate their own translation. The two proteins form a L10-L12 complex that is able to bind specifically to the leader sequence of the L10 operon mRNA and prevent translation. We show that the leader sequence: (i) is required for the translation of mRNA into L10 and L12 proteins; and (ii) contains a unique binding site for the inhibitory L10-L12 complex. We suggest that a specific secondary structure of the leader RNA is required for translation. When this structure is perturbed by L10-L12 binding, by deletion, or point mutations, translation is inhibited. The block on the synthesis of L10 and L12 can presumably be removed by the incorporation of the inhibitory L10-L12 complex into assembling 50S ribosome subunits. We observed that rRNA prevents the binding of L10-L12 to the mRNA. Furthermore, we have identified extended sequence homologies within the 23S rRNA and L10 leader region RNA. The L10-L12 binding site on the mRNA includes part of the homologous sequences.

Bacterial Proteins↗

The main photosensitizing components of hematoporphyrin derivative.

Commercial hematoporphyrin (Hp) and the tumor-localizing and photosensitizing agent hematoporphyrin derivative (Hpd) were analysed by means of high pressure lipid chromatography (HPLC). Furthermore, their efficiencies in sensitizing the photoinactivation of human cells in vitro were compared. The comparison showed that the least polar components of Hpd played the major role in this sensitization. In Hpd solutions used for injection in photochemotherapeutic treatment of cancer, these active components seem to be present as aggregates.

Cell Line↗

Porphyrin-sensitized photoinactivation of human cells in vitro.

NHIK 3025 cells derived from a carcinoma in situ were exposed to hematoporphyrin derivative (Hpd) and light and examined by light microscopy, freeze-etching, scanning, and transmission electron microscopy. The first morphologic changes observed were shrinkage of mitochondria and formation of vesicles on the cell membrane. Furthermore, increased membrane permeability led to accumulation of Hpd and cellular swelling, with a concomitant reduction in the number and size of the microvilli. Some of the vesicles seemed to originate from microvilli. The freeze-etching appearance of the membranes of the majority of the cells was unaltered by treatment with Hpd and light. However, in some cases clustering of membrane particles was observed. At low doses membrane vesiculation and cell swelling were reversed within a few hours after treatment, indicating that repair processes were operative.

Carcinoma in Situ↗

Release of lysosomal enzymes and lactate dehydrogenase due to hematoporphyrin derivative and light irradiation of NHIK 3025 cells in vitro.

NHIK 3025 cells in monolayer cultures were irradiated with near ultraviolet light in the presence of hematoporphyrin derivative (HPD). The release of lysosomal enzymes and the cytosol marker enzyme lactate dehydrogenase to the culture medium was determined 1, 3, 6 and 24 hours after irradiation. The enzyme activities of the cell pellet were investigated 24 hours after irradiating the cells. After exposure of HPD-labelled cells to light doses causing no cell inactivation, the leakage of enzymes was slightly inhibited in the first 6 hours followed by a period between 6 and 24 hours when the cells released the same amount or slightly more enzymes than the control. The enzyme activities of cell pellets made 24 hours after exposure were 40-75% of control values due to either a small inhibition of cellular enzyme activity or of inhibited cell growth by this dose. A higher light dose inactivating 80-90% of the cells, caused a rapid release of both lysosomal and cytosol enzymes. The cell pellets contained very little of the enzymes 24 hours after treatment and especially free intracellular enzymes had been released with high efficiency. Leupeptin, a lysosomal protease inhibitor, did not protect the cells from inactivation. We conclude that the release of lysosomal enzymes after porphyrins and light is of little significance in terms of cell killing.

Acetylglucosaminidase↗

Photodynamic effects on human cells exposed to light in the presence of hematoporphyrin. Localization of the active dye.

Human cells of the line NHIK 3025 were exposed to light in the presence of hematoporphyrin. Cellular inactivation, induction of single-strand breaks in the DNA and cellular uptake of hematoporphyrin were measured under different conditions. It was concluded that hematoporphyrin bound to or taken up by the cells leads to photoinactivation and photoinduction of single-strand breaks in the DAN, while hematoporphyrin present in the medium outside the cells is of no significant importance.

Cell Line↗

Uptake of hematoporphyrin derivative and sensitized photoinactivation of C3H cells with different oncogenic potential.

Four types of mouse embryo fibroblast cells of different oncogenic potential were investigated with respect to uptake of the tumor localizing agent hematoporphyrin derivative (Hpd) and sensitized photoinactivation. Cell size and cellular content of Hpd were measured simultaneously for single cells by means of flow cytofluorimetry. The more malignant cell types had a slightly higher porphyrin uptake per unit cellular volume than the untransformed type, while the photosensitivity of cells incubated with Hpd was equal for all the cell types. Since Hpd seems to concentrate in membranes, this may be related to the fact that the membrane areas of malignant cells are relatively larger than that of untransformed cells, due to the presence of more microvilli. The present study indicates that the preferential localization of Hpd in tumors, as well as the high efficiency of phototherapy reported in the literature, are due to extracellular differences between the tumors and normal tissue.

9,10-Dimethyl-1,2-benzanthracene↗

Multiplication of human NHIK 3025 cells exposed to porphyrins in combination with light.

Cells from the established line NHIK 3025 were exposed to haematoporphyrin derivative and light. After this photodynamic treatment the first interphase of surviving cells was prolonged. Furthermore, a pronounced effect on the progression through the first mitosis was observed. Mainly the duration of metaphase was increased. Some of the cells were irreversibly arrested in mitosis and the cells that were able to complete mitosis after treatment multiplied in the subsequent generations at the same rate as the control. Cells treated in the late stages of the mitosis went out of mitosis at the same rate as the control. This indicates that the treatment with porphyrins and light induces a block in a specific stage of mitosis.

Carcinoma in Situ↗

Photodynamic effects of haematoporphyrin derivative on synchronized and asynchronous cells of different origin.

Phototherapy in the presence of haematoporphyrin derivative has been shown to have a preferential effect on malignant tumours when compared to normal tissue. This communication presents a comparison of the sensitivity to photochemotherapy in vitro of different cell lines. Asynchronous populations of cells were exposed to light in the presence of haematoporphyrin derivative, and found to be inactivated with a comparable efficiency. The lines were of human, Chinese-hamster or mouse origin and had different abilities to form tumours after heterotransplantation into nude mice or transplantation into syngeneic, immunosuppressed mice. Synchronized cells from 4 of the lines showed a similar variation in sensitivity to light throughout the cell cycle. Cells near the middle of interphase showed the highest sensitivity, whilst cells in early G1 were found to be least sensitive towards treatment with haematoporphyrin derivative and light.

Animals↗