Search PubMed⌕ Search

Biomedical subjects

L Granholm

Publications and source records attributed to L Granholm.

At least 19 recordsLinked to original sources

Induction of GFAP production in human glioma lines grafted into the anterior chamber of the rat eye.

Three established glial fibrillary acidic protein (GFAP)-negative cell lines from human gliomas were transplanted to the anterior chamber of the rat eye. Short-term survival was seen with all transplants. The cells expressed GFAP following transplantation. For comparison, 4 GFAP-positive cell lines were transplanted. With grafting of 5000 cells of any of 6 bipolar cell lines, the transplanted cells could be seen to develop multiple, slender processes reminiscent of mature astrocytes. When 50,000 cells were grafted, vascularized cell mats covering the corneae were seen. The induction of GFAP production and the phenotypic changes were interpreted as signs of differentiation induced by the new environment. All transplanted cells were rejected after 8 weeks.

Animals↗

Prolonged survival and vascularization of xenografted human glioblastoma cells in the central nervous system of cyclosporine A treated rats.

Glioblastoma cells from three established lines were transplanted in oculo and in cerebrum to rat hosts. A very low dose of Cyclosporine A was found sufficient to allow graft survival whereas grafts in non-immunosuppressed animals did not survive. Moderate immunosuppression permitted long term graft survival without aggressive growth of glioblastoma cells, creating a protracted course during which neither cell rejection nor tumor proliferation occurred. A tumor reminiscent of a glioblastoma was only seen in one animal on high immunosuppression. Phenotypic changes such as the induction of glial fibrillary acidic protein (GFAP) production and an astrocytic morphology were observed in the cells growing in oculo but not in cerebrum. Vascularization was easily demonstrated with laminin immunofluorescence but the endothelial proliferation typical of glioblastomas was not seen.

Animals↗

Sialyllactotetraosylceramide, a ganglioside marker for human malignant gliomas.

The ganglioside composition of surgically removed human glioma tissue was shown to differ from that of normal adult brain tissue. First, it contained reduced amounts of the major normal brain gangliosides of the gangliotetraose series. Second, it contained increased proportions of gangliosides not detected in normal brain tissue. One of these was isolated and established as being sialyllactotetraosylceramide 3'-isoLM1. Radioimmunoassay for this ganglioside antigen in human glioma tissue revealed that 14/14 specimens of grades III and IV were positive but only 1/4 of grade II. Normal brain tissue was negative. These results suggest that sialyllactotetraosylceramide is a marker for human malignant gliomas.

Antigens, Neoplasm↗

Potential ganglioside antigens associated with human gliomas.

Gangliosides in human gliomas were investigated and found to have an altered composition and concentration as compared to normal grey and white matter of brain. The major gangliosides GM1, GD1a, and GT1b were markedly reduced in the tumour tissue and in contrast there was an increase of gangliosides GM3 and GD3, which often appeared as the dominating ones. Moreover, the tumours contained gangliosides, both mono- and oligosialylated, which could not be detected in the normal brain. The concentration of gangliosides, 0.7 +/- 0.4 mumol sialic acid/g, was significantly lower as compared to normal brain grey (p less than 0.001) and white matter (p less than 0.01), which contained 3.5 +/- 0.3 and 1.2 +/- 0.3 mumol sialic acid/g respectively. The tumour tissue concentration of phospholipids was 14 +/- 8 and of cholesterol 19 +/- 12 mumol/g. The appearance in glioma tissue of gangliosides that are not found in normal brain tissue suggests that these are tumour associated and might serve as surface antigens detectable by specific monoclonal antibodies.

Adult↗

Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver glucocorticoid receptor.

By means of a monoclonal antibody against the rat liver glucocorticoid receptor (GR) in combination with the indirect immunoperoxidase technique it has been possible to demonstrate GR-immunoreactive nerve and glial cell nuclei all over the tel- and diencephalon of the male rat. Strongly GR-immunoreactive nerve cell nuclei were only present in the parvocellular part of the paraventricular hypothalamic nucleus, in the anterior periventricular hypothalamic nucleus, in the ventral part of the mediobasal hypothalamus, and in the CA1 and CA2 subregion of the hippocampal formation. Within the paraventricular hypothalamic nucleus a substantial overlap exists between the GR-immunoreactive area and the CRF-immunoreactive area. Medium to high densities of moderately GR-immunoreactive nerve cell nuclei were present all over the cortical hemispheres. Medium densities of moderately GR-immunoreactive nerve cells were demonstrated in many thalamic nuclei and in the central amygdaloid nucleus. After adrenalectomy the GR immunoreactivity was predominantly located in the pericaryon. Upon acute corticosterone treatment of adrenalectomized male rats, the GR immunoreactivity was again mainly demonstrated in the nerve cell nuclei indicating that corticosterone can translocate GR from the cytoplasm to the cell nuclei. It is suggested that the hypothalamic GR may be involved in the regulation of especially CRF secretion but also in the secretion of other anterior pituitary hormones such as TRH and somatostatin.

Adrenalectomy↗

Evidence of prolactin receptors in the choroid plexus and a possible role in water balance in neonatal brain.

Tissue dehydration, including that of the brain, is a natural part of maturation. In the newborn it is accompanied by an acute salt water diuresis which is particularly pronounced in the premature infant. The decrease in cranial volume and fall in intracranial pressure to subatmospheric levels observed in premature infants after birth suggests that the brain shares in this process. Since fluid homeostasis is normally under hormonal control, the inordinate loss of fluid in the prematurely born may be attributable to a hormonal imbalance. The possibility that prolactin, a proven osmoregulatory hormone in submammalian species but not in mammals and primates, may have an important role in this process is suggested by recent evidence that prolactin regulates tissue water in fetal and newborn animals. If this hormone assists in the regulation of water and electrolyte content of the brain during the perinatal period then prolactin receptors might be expected at blood-brain and blood-CSF barriers. Our study with preterm, term and adult rabbits indicates that prolactin receptors are present and in much higher concentrations in the choroid plexus than in other tissues examined. Specific binding of prolactin to receptors on tissues normally is observed to increase with age. Since binding to the choroid plexus decreased with age it would suggest that the effect of prolactin on choroid plexus function may be more important during the perinatal than later stages of development.

Age Factors↗

Effect of dexamethasone treatment on volume and contrast enhancement of intracranial neoplasms.

In a prospective study the effect of dexamethasone treatment on tumor volume and contrast enhancement was evaluated by computed tomography (CT) in 15 patients with intracranial lesions. Histological diagnoses were confirmed in 13 patients who had undergone surgical intervention. A CT study of the head, with and without contrast medium, was performed prior to the dexamethasone treatment and at various intervals during the treatment for 8-19 days. The volume, attenuation, and contrast enhancement of the tumor were measured and related to the time after the start of the treatment. In six meningiomas there was no change in the volume and enhancement of the tumors. Out of four gliomas, there was an increase in volume of two tumors, whereas the other two cases showed a decrease in the tumor volume. In one glioma a distinct decrease in enhancement was observed. In three cases of metastasis a decrease in enhancement and tumor volume was noted. An acoustic neurinoma and an unverified lesion, considered radiologically to be a glioma, also showed a decrease in tumor volume and contrast enhancement. In tumors that responded to the treatment, a decrease both in volume of the tumor and peritumoral brain edema as well as a decrease in contrast enhancement of the tumor were observed.

Adult↗

Estrogen and progestin receptors in intracranial meningiomas.

Tissue samples from 16 meningioma patients were analysed for the cytosolic estrogen receptor concentration using isoelectric focusing and 11 of the 16 cases were also analysed for the cytosolic progestin receptor concentration using sucrose gradient centrifugation. In this study, 15 of the 16 (94%) and 9 of the 11 (82%) meningiomas had detectable estrogen and progestin receptors, respectively. The mean estrogen receptor concentration in female subjects was 8.9 fmol/mg protein and in males 3.0 fmol/mg protein. This sexual difference in receptor content was statistically significant. When the progestin receptor concentrations were plotted against the estrogen receptor concentrations in the same tumors, a relatively good positive correlation was obtained in female patients (r = 0.87). These findings confirm and extend previous reports on the existence of sex steroid receptors in human brain tumors and might open up the possibility of selective endocrine therapy against meningiomas, especially in case of poor-risk patients.

Adult↗

A qualitative comparison of the glucocorticoid receptor in cytosol from human brain and rat brain.

The glucocorticoid receptor in cytosol from human brain was studied using isoelectric focussing in slabs of polyacrylamide gel. [3H]Dexamethasone was used as tracer for receptor analysis. The glucocorticoid receptor from human brain was compared to the glucocorticoid receptor in rat brain. A similar peak of radioactivity with a pI of about 6.1 was obtained by isoelectric focussing of cytosol from both human brain and rat brain. The trypsin-induced fragmentation patterns of the glucocorticoid receptor from human brain and rat brain were very similar when analyzed by isoelectric focussing. The hormone specificity of the glucocorticoid receptor in human brain and in rat brain cytosol was compared by competition experiments using unlabelled dexamethasone, betamethasone, cortisol and corticosterone as competitors. No difference between human brain and rat brain cytosol was detected. It is concluded that the hormone specificity and the protein structure of the glucocorticoid receptors in human brain and in rat brain are similar.

Adrenalectomy↗

A study of glucocorticoid receptors in intracranial tumors.

Tissue samples from 20 patients with various intracranial tumors and one case of cerebral contusion were analyzed for the cytosolic glucocorticoid-receptor concentration using isoelectric focusing in slabs of polyacrylamide gel. It is pointed out that the clinical response to dexamethasone in brain edema associated with various intracranial lesions is, to some extent, parallel to the glucocorticoid-receptor concentration in these tumors. The findings in this investigation suggest that the cytosolic glucocorticoid receptor might be responsible for the initiation of a series of biochemical effects of steroids affecting brain edema. It is possible that the first step in eliciting a beneficial clinical response to dexamethasone in patients with brain tumors is the formation of a steroid-receptor complex in the peripheral parts of the tumor.

Adolescent↗

On pathogenesis of symptoms in Ménière's disease.

A conception of the mechanism for initiating symptoms in Ménière's disease has been forwarded. According to this conception production of endolymph may vary also in normals. The hydrops in Ménière cases is brought about by a relative insufficiency in endolymphatic draining routes and the hydrops presents itself only at peak endolymph production periods. The attacks of vertigo are brought about at the distension of the sacs as well as of the regaining of normal shape of the sacs. The mechanism causing the vertigo could be an effect of mechanical push-and-pull effect on the sensory epithelium of the cristae. The early low-tone hearing loss and the persistant normal caloric reactivity also in advanced Méière cases may be due to simple physical laws : distensions of sacs with equal walls will more easily be brought about in wider than narrow compartments.

Dilatation, Pathologic↗

Lars Leksell.

Explore the source record for details and available documents.

Animals↗