Biomedical subjects

T Stigbrand

Publications and source records attributed to T Stigbrand.

239 records · Page 14Linked to original sources

PubMedDate not supplied

Prenatal low-dose gamma irradiation of the inner ear induces changes in the expression of intermediate filaments.

The expression of intermediate filaments (1F) was analysed in the inner ear in normally developed adult CBA/CBA mice and in mice of the same age which had been gamma irradiated in utero with a low dose 1-2 Gy single exposure. Well characterized monoclonal antibodies (mAbs) against all classes of intermediate filament proteins (cytokeratins-Cks, vimentin, neurofilaments, desmin and glial fibrillar acidic protein) were used. With the exception of neurofilament proteins, the expression of intermediate filament proteins was the same in adult normal and irradiated inner ears, irrespective of gestational age at exposure. A complex Ck pattern occurred in the various cell types comprising the membranous labyrinth. In spite of the differences in cell shape and internal organization of organelles, epithelia actively involved in inner ear fluid homeostasis (stria vascularis, dark cell epithelium, endolymphatic duct and sac) revealed, according to our mAbs, the same expression of Cks, except for the mouse counterpart of human Ck 7, which was found exclusively in the stria vascularis and the endolymphatic duct and sac. The pattern of intermediate filament composition in the labyrinth was the same in the mouse as in man. Irradiation on gestational days 12 or 13 (the otocyst stage)--but not at more advanced embryonic age--induced immunoreactivity for neurofilament proteins in vestibular hair cells (HC) and to a minor extent also in cochlear HC. No such positivity was found in the control material.

Abnormalities, Radiation-Induced↗

PubMedDate not supplied

Cytokeratin diversity in epithelia of the human inner ear.

The expression of cytokeratins (Cks) nos. 5, 7, the combination 5 and 8, 8, 10, 17, 18 and 19 was analysed in the inner ear of 14-24-week-old human fetuses, using 10 different well characterized monoclonal antibodies (mAbs). A complex pattern of Ck immunoreactivity was found. Cks 8 and 18 were identified in both cochlear and vestibular hair cells as well as in all other epithelia. Epithelia involved in fluid regulation (stria vascularis, Reissner's membrane and dark cell epithelium) revealed the same pattern of Ck immunoreactivity in spite of morphological differences in cell configuration. A specific Ck, no. 10 as detected with the mAbs RKSE 60, was found in the endolymphatic duct and sac. The expression of Cks in the human inner ear is in principle similar to that found in the labyrinth of other animal species, for instance in the mouse. However, the human inner ear had a more complex pattern than any inner ear so far known in animal species.

Antibodies, Monoclonal↗

PubMedDate not supplied

Inhibition of growth of HeLa cell tumours in nude mice by 125I-labeled anticytokeratin and antiPLAP monoclonal antibodies.

The radiommunotherapeutic potential of 125I-labeled monoclonal antibodies was investigated in 48 nude mice (BALB/c, nu/nu) inoculated s.c. with the HeLa Hep 2 human adenocarcinoma cell line. This isotope, 125I, which is not commonly used for therapeutic purposes caused significant decrease in tumour growth from day 10 to day 42, when coupled to monoclonal antibodies directed against placental alkaline phosphatase (H7) or cytokeratins (TS1). The average growth rate was approximately 50-60% of that observed in the untreated control group after 42 days. The specific radioactivity in each organ 42 days after injection of radiolabeled monoclonal antibodies, indicated that these target antigens retain significant amounts of radiolabeled antibody in the tumours for at least 6 weeks after injection. No weight loss was seen in the animals during this experiment. By use of autoradiographic techniques, the labeled monoclonal antibodies were visualized deep in tumours in characteristic patterns representative of viable tumour cells (H7) and necrotic areas (TS1). The therapeutic approach using 125I labeled antibodies is encouraging and may offer new dimensions in radioimmunotherapy.

Adenocarcinoma↗

PubMedDate not supplied

Protein kinase inhibitors exert stage specific and inducer dependent effects on HL-60 cell differentiation.

The human promyelocytic leukemia cell line HL-60 was induced to differentiate to mature granulocytic cells by dbcAMP or RA. The influence of distinct protein kinases during different stages of this differentiation was studied by the use of H8, staurosporine and genistein as inhibitors of PKA, PKC and PTK respectively. In dbcAMP-mediated differentiation, the PKA activity of uninduced cells is crucial for the induction of differentiation, but therefore its significance drastically declines and a more important role is played by PKC and PTK. In RA-mediated differentiation, the native state of PKA and PKC activities are necessary and of similar importance for induction. However, the differentiation is enhanced when, following induction, the activities of PKA and PTK are normal and the activity of PKC, in contrast, is temporary suppressed. At the phenotypic stage the effect of inhibition of protein kinases on maturation is in the order PTK > PKC > PKA for the dbcAMP-mediated differentiation and PKC > PKA > PTK for the RA-mediated differentiation. The results indicate that protein kinase activities during differentiation are stage specific and this specificity depends on the inducer used.

Alkaloids↗

PubMedDate not supplied

Relationship between differentiation mechanisms involving cAMP-dependent protein kinase and protein kinase C in uninduced and differentiating HL-60 cells.

The influence of protein kinases on the differentiation of a human promyelocytic leukemia-cell line HL-60 to granulocytes was studied by using H8 and staurosporine as inhibitors of PKA and PKC respectively. In order to determine the significance of these protein kinases of uninduced and differentiating cells for the final differentiation, the cells were treated with the inhibitors before (-24 hours-0 hours) and after induction (0 hour-96 hours) of differentiation. To elucidate potential "cross-talking" between PKA and PKC of uninduced and differentiating HL-60 cells, the effects of H8 and staurosporine on differentiation were further examined by exposing the cells, pretreated with inhibitors for approximately one cell cycle time before induction, to the same or a different inhibitor. The results demonstrated that the effects of the inhibition of protein kinases of these cells on differentiation are protein kinase and inducer dependent. There is also inducer-dependent "cross-talk" between the differentiation mechanisms involving PKA and PKC activities in uninduced HL-60 cells and in cells induced to differentiate by dbcAMP or RA. However, the data also demonstrate that the PKC activity of uninduced cells involved in the differentiating mechanisms is not related to the PKC activity of dbcAMP-mediated differentiation and PKA is not related to PKC, respectively, in RA-mediated differentiation. The effects of the pretreatment of HL-60 cells with dbcAMP or RA for 24 hours on their subsequent differentiation induced by dbcAMP or RA are different. The pretreatment of cells with dbcAMP strongly potentiates RA-mediated differentiation, while the pretreatment with RA suppresses twofold dbcAMP-mediated differentiation.

Bucladesine↗