Subcellular distribution of zinc in islet beta-cell fractions.
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Animals↗
Biomedical subjects
T Andersson
Publications and source records attributed to T Andersson.
The role of viral glycoproteins in mumps-virus-dependent lymphocyte-mediated cytotoxicity in vitro.
Human peripheral blood lymphocytes (PBL) from healthy donors express enhanced natural cytotoxicity to target cells after a brief exposure to mumps virus in vitro. We describe here experiments aiming at elucidating the mechanism of this virus-dependent cytotoxicity. Treatment with proteolytic enzymes resulted in virus particles depleted of one or both kinds of their glycoproteins spikes. Removal of both of these components frrom the virion abrogated their ability to enhance cytotoxicity. This virus-dependent cytotoxicity was significantly but not completely reduced when one of the spike glycoproteins (gp 75, HANA) was removed selectively. Similarly, nucleic-acid-free preparations of the spikes, obtained by detergent treatment of mumps virions, also elicited enhanced cytotoxicity. However, the activity of these preparations was lower than that of untreated virions. Further evidence for the importance of HANA was provided by the use of (F(ab')2 fragments of anti-HANA-specific rabbit antibodies. When these fragments were allowed to react with virus before addition of the virus to PBL, no augmentation of cytolysis was observed. Antibody fragments specific for the other spike protein (gp 61, F) failed to inhibit the virus-dependent enhancement of PBL-mediated cytotoxicity. However, anti-HANA and anti-F blocked this reaction when added directly to the mixture of virus-treated PBL and target cells. The results are compatible with the hypothesis that virus-dependent cytotoxicity requires HANA for anchoring the virus to PBL receptors (and perhaps to bring effector and target cells into closer contact), whereas F may be involved in subsequent events increasing effector cell function.
Antigens, Viral↗
Effect of Fc-receptor modulation on mumps-virus-dependent lymphocyte-mediated cytotoxicity in vitro.
The natural cytotoxicity of peripheral blood lymphocytes (PBL) from normal human donors to a variety of tissue culture target cells increases upon brief exposure of lymphocytes to mumps virus. The effector cells operative in this system have Fc receptors for IgG (FcR), since cytotoxicity was abolished when FcR+ cells were removed by passage of the lymphocyte over immune-complex columns. When PBL were treated with immune complexes for 16 h at 37 degrees C, their FcR activity was sharply decreased (modulation), as indicated by a significantly reduced capacity of the treated cells to display antibody-dependent cytotoxicity (ADCC). Modulation had variable effects on natural cytotoxicity. In contrast, the virus-dependent cytotoxicity above the natural cytotoxicity remained essentially unchanged, indicating that a functionally intact FcR is not required in this system for carrying out cytolysis.
Antibody-Dependent Cell Cytotoxicity↗
Perchlorate binding to cytochrome c: a magnetic and optical study.
1. The effects of perchlorate on cytochrome c have been investigated by 1H and 35Cl NMR, electron paramagnetic resonance and optical spectroscopy. 2. The pK values for the formation and disappearance of the major alkaline conformation were found to be displaced from 9.3 to 8.3 and from 10.4 to 10.9, respectively. The displacement was dependent on the ClO4(-) concentration below 0.1 M. 3. Competition experiments between perchlorate and chloride show that ClO4(-) binds both to the neutral and alkaline forms but with a higher affinity for the latter. The appearance of a new binding site in the alkaline form accounts for the markedly enhanced relaxation rate of 35ClO4(-) in this pH range. Complex formation between cyanide and the alkaline species results in the loss of this binding site, which probably is located close to or within the heme crevice. 4. The neutral form of ferricytochrome c also binds perchlorate strongly as evidence by the unique appearance of a high-spin signal dependent on pH and perchlorate concentration. This signal disappears with the same pK value as the neutral form. The effects of perchlorate on cytochrome c are due to specific binding of this ion.
Animals↗
Ca2+ transport in pancreatic beta-cells during glucose stimulation of insulin secretion.
The role of Ca2+ in the regulation of insulin secretion was evaluated using beta-cell-rich pancreatic islets isolated from ob/ob-mice. The glucose stimulation of the secretory activity is supposed to result from accumulation of Ca2+ in the submembrane cytoplasmic space. It is likely that this process reflects the balance between increased entry of Ca2+ into the beta-cells and an enhanced sequestration of Ca2+ in the organelle sinks. The proposed model can explain the cAMP potentiation of glucose-stimulated insulin release with suppression of the mitochondrial Ca2+ uptake. Furthermore, differences in the Ca2+ buffering capacity of the secretory granules may account for other characteristic features of glucose-stimulated insulin release, in particular its biphasic nature and sensitivity to suppression on withdrawal of nutrients.
Adenosine Triphosphate↗
Calcium movements in relation to glucose-stimulated insulin secretion.
The influence of glucose on the beta-cell handling of Ca2+ was studied in pancreatic islets isolated from ob/ob mice. Glucose had both stimulatory and inhibitory effects on the washout of radioactivity from islets preloaded with 45Ca. Although the phenomenon of stimulation may be essentially associated with an increased turnover of 45Ca incorporated in response to glucose, the inhibitory effect might merely reflect a lowering of Ca2+ in the cytoplasm following from its accumulation into secretory granules and mitochondria. It is suggested that the Ca2+ uptake by the granules is mediated by an ATP-dependent proton gradient and that these organelles serve as a regulator of the cytoplasmic Ca2+ involved in stimulus-secretion coupling. Alterations in the beta-cell handling of Ca2+ may not only explain the role of glucose as an initiator of insulin release, but also the potentiation by cAMP of the action of glucose. The latter effect can tentatively be ascribed to an increase of cytoplasmic Ca2+ following cAMP-induced inhibition of the net Ca2+ uptake by mitochondria.
1-Methyl-3-isobutylxanthine↗
[Septicemia and purulent meningitis in splenectomized patients].
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Adult↗
Ion binding to cytochrome c studied by nuclear magnetic quadrupole relaxation.
The enhancement of the 35Cl- transverse relaxation rate on binding of chloride ions to oxidized and reduced cytochrome c has been studied under conditions of variable sodium chloride concentration, temperature, pH, sodium phosphate, iron hexacyanide, and sodium cyanide concentration. The results revealed the presence of a strong binding site(s) for chloride in both oxidized and reduced cyt c, with a higher affinity in ferrocytochrome c. Competition experiments suggest that these sites also bind iron hexacyanide and phosphate. Cyanide binding to the iron in ferricytochrome c at alkaline and neutral pH was shown to decrease the binding of chloride. The pH dependence of the 35Cl- relaxation rate has been fitted by using literature pK values for ionizable groups. No indications of Na+ binding to oxidized and reduced cytochrome c have been observed by using 23Na+ NMR. Our results suggest that chloride is bound near the exposed heme edge and that the surface structure or dynamics in this region are different in the two oxidation states.
Chlorides↗
Intra-arterial chemotherapy of malignant head and neck tumours with superselective angiographic technique.
A technique is described for repeated superselective angiographic infusion of anticancer drugs into advanced malignant tumours of the head and neck region. The technique allows for a high concentration of the drug in the tumour and, furthermore, it is possible to ensure that the infused anticancer drug adequately reaches the tumour. Mitomycin C was given to 15 patients with advanced malignant tumours of the head and neck region. In 16 patients a partial remission was seen, and in another 5 patients a subjective improvement was reported. No complications were observed.
Adult↗
Undifferentiated giant and spindle cell carcinoma of the thyroid. Report on two combined treatment modalities.
Undifferentiated giant and spindle cell carcinoma of the thyroid is a rapidly fatal disease. Most patients die from local tumour progression and with distant metastases. A combination of debulking surgery, irradiation and combination chemotherapy is reported. An improvement of the local results of treatment was observed. A combination of irradiation and chemotherapy resulted in local control in only one of 8 patients. Therefore, debulking surgery was added in the next 5 patients and a local control was achieved in 4.
Aged↗
5 years' experience of 5-S-cysteinyldopa in melanoma diagnosis.
Determinations of the urinary excretion of 5-S-cysteinyldopa were performed in 571 patients previously treated by surgery for melanoma or melanoma metastasis. 90% of the 161 patients with metastases showed values exceeding 0.15 mg/24 h, and 9% of the 410 patients without metastases had such values. The increase in 5-S-cysteinyldopa excretion was generally more pronounced in men with metastases than in women, 98% of the men and 77% of the women with metastases showing values exceeding 0.15 mg/24 h. High levels of 5-S-cysteinyldopa are of grave prognostic significan4% died within one month, and only 3% survived for more than a year. In Sweden, determination of 5-S-cysteinyldopa in patients operated on for melanoma gives maximum information in the winter (October--March), when sun exposure does not influence the excretion levels.
Adult↗
Calcium and pancreatic beta-cell function. 4. Evidence that glucose and phosphate stimulate calcium-45 incorporation into different intracellular pools.
beta-Cell-rich pancreatic islets were microdissected from ob/ob-mice and used for studies of 45Ca uptake and washout. Irrespective of whether the experiments were performed at 21 or 37 degrees C both glucose and phosphate stimulated the net uptake of lanthanum-nondisplaceable 45Ca. The stimulatory effect of phosphate was additive to that produced by glucose. 45Ca incorporated in response to phosphate differed from that taken up in the presence of 20 mM glucose in being easily washed out although it was not affected by the glucose concentration of the washing medium. The efflux of 45Ca was reduced after introducing phosphate into a medium used to perifuse islets which had accumulated 45Ca in response to 20 mM glucose. This suggests that the outward calcium transport can be influenced also by intracellular trapping of the cation. The glucose-stimulated insulin release was inhibited by phosphate; an effect reversed by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. It is concluded that a common effect of glucose and phosphate is to trap calcium in the pancreatic beta-cells but that there are fundamental differences between their effects on intracellular distribution of calcium and on insulin release.
Animals↗
Treatment of traumatic arthritis in the horse with intra-articular orgotein (palosein).
A total of 134 horses of various breeds were treated for aseptic arthritis of traumatic origin using Orgotein (Palosein). The drug was injected into 192 affected joints of these animals. Recovery rates of 94 per cent were recorded in cases which had shown lameness for less than 2 months before treatment commenced and 49 per cent in those lame for longer than 2 months.
Animals↗
En-bloc irradiation of tumours of the head and neck and their lymphatics. II. Early results and side effects.
The results and side effects of en-bloc irradiation of ear, nose and throat tumours and their lymphatics showed that the technique had been successful in nasopharyngeal carcinoma, but poor in carcinoma of the hypopharynx. Marked early and late radiation side effects were relatively common in high age and with certain tumour sites, whereas no correlation could be demonstrated with total absorbed dose, fractionation, cumulative radiation effect or major surgery.
Aged↗
Immunoglobulin-independent natural cytotoxicity of Fc receptor-bearing human blood lymphocytes to mumps virus-infected target cells.
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Adult↗
Enhanced cytotoxicity of human lymphocytes against rabies-infected cells by rabies-specific antibodies.
Human anti-rabies immune sera enhanced the in vitro cytotoxicity of human lymphocytes against rabies virus-infected green-monkey kidney cells. The immune sera were collected from patients immunized with rabies vaccine produced either in human diploid cells or in nervous tissue. Significant cytotoxicity was observed even with high serum dilutions, indicating that the K-cell assay might be a sensitive tool for detection of anti-rabies antibodies.
Animals↗
Interactions between human lymphocytes and paramyxovirus-infected cells: adsorption and cytotoxicity.
The capacity of human lymphocytes to adhere to paramyxovirus-infected monolayers and their capacity to kill paramyxovirus-infected cells was investigated. A large fraction of human lymphocytes was found to adhere firmly to the paramyxovirus-infected monolayers. Predsorption of lymphocytes on mumps virus-infected cells impaired their adsorption to a second cell monolayer of the same type. The cytotoxic activity of lymphocytes against mumps virus-infected cells was also reduced after predsorption on mumps virus- or Newcastle disease virus-infected (NDV) cell monolayers. Exposure of lymphocytes to trypsin did not significantly decrease either adsorption or cytotoxicity. Pretreatment of lymphocytes with neuraminidase (NANase) partly inhibited adsorption whereas cytotoxicity was not decreased. Cell fractionation experiments after rosetting of the lymphocytes with sheep erythrocytes (E) indicated that T cells were equally or better adsorbed than "non-T" cells. Taken together with previous experiments which showed that the majority of T lymphocytes are not cytotoxic against mumps virus-infected cells these results suggest that adherence of lymphocytes to infected cells and cytotoxicity may be unrelated phenomena.
Antigens, Viral↗
5-S-cysteinyldopa in the urine of melanoma patients.
A newly discovered amino acid, 5-S-cysteinyldopa, present in the urine of healthy subjects is excreted in pathological amounts in many patients suffering from melanoma metastases. Increased excretion of 5-S-cysteinyldopa may be observed before metastases become clinically evident. Determination of 5-S-cysteinyldopa is superior to determination of dopa+dopamine in the diagnosis of melanoma metastases.
Adult↗