Basaloid squamous cell carcinoma of the palate.
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Biomedical subjects
Publications and source records attributed to C Nilsson.
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A circadian variation in human cerebrospinal fluid (CSF) production has recently been demonstrated using magnetic resonance phase imaging. A nightly peak in CSF production was found at approximately 0200, when production is approximately twice the daytime values. In the present study, we have investigated the effect of a beta 1-receptor antagonist, atenolol, on the production of CSF, specifically the nocturnal production peak. CSF production was measured in fourteen healthy volunteers of both sexes in the time interval 1500-1800, with or without drug administration (100 mg orally) at 1800, and a second measurement was made in the time interval 2300-0200. In the absence of drug administration, all nine volunteers showed a significant increase in CSF production at night, from 0.34 +/- 0.06 ml/min in the time interval 1500-1800 to 0.61 +/- 0.05 (SE) ml/min (P < 0.005), confirming the presence of a circadian variation in these individuals. One week later, the experiment was repeated in five of these volunteers, plus an additional five volunteers, but with the administration of 100 mg atenolol orally immediately after the first measurement (at 1800). In five of the volunteers a decrease in CSF production was seen at midnight compared with daytime production values; in two volunteers CSF production remained unchanged, while three volunteers showed increased production. The average CSF production was 32% lower at night (0.27 +/- 0.10 ml/min) compared with the afternoon (0.40 +/- 0.07 ml/min), after administration of atenolol (P = 0.37).(ABSTRACT TRUNCATED AT 250 WORDS)
Rats were made hypo- or hyperthyroid to study the role of thyroid hormones on cerebral transthyretin (TTR) mRNA expression. TTR mRNA was detected by Northern blot in rat liver, choroid plexus and meninges but not in cultured astrocytes or cultured cerebral endothelial cells. No changes were found in the levels of TTR mRNA in liver, choroid plexus or meninges in hypo- or hyperthyroid rats compared with the controls. In order to investigate the main route of thyroxine transport from blood to brain, the distribution of [125I]thyroxine in the brain was studied after intravenous (i.v.) and intraventricular (i.v.c.) injection by both direct counting and autoradiography. While distribution of [125I]thyroxine could be seen throughout the brain parenchyma after i.v. injection, the labelling was confined to the CSF spaces after i.v.c. administration. When protein synthesis was inhibited by cycloheximide treatment and [125I]thyroxine was injected intravenously, the uptake of [125I]thyroxine in the choroid plexus decreased while the uptake in the cerebral cortex increased. This indicates that thyroxine is transported into the brain primarily through the blood-brain barrier and not via the choroid plexus and CSF. We discuss the possibility that TTR has a role in the distribution of thyroxine throughout the brain.
The present study compares spinal configuration, spinal range of motion and joint mobility in first-year students of the Swedish Ballet School and in nondancing students of corresponding age and sex in a state school. The study comprises all the first-year (fourth grade) students (n = 23) at the Swedish Ballet School: 11 boys and 12 girls. Their dance practice time was 10 h per week. Thirty-six children in the fourth grade at a state school comprised the control group. None of the controls took ballet classes or participated in organised gymnastics out of school. The neutral spine configuration in standing and the sagittal spine mobility were measured using Debrunner's kyphometer and Myrin's inclinometer. Joint laxity was measured by employing a modified form of the Contompasis method. Compared with the controls, the dancers showed a higher incidence of joint hypermobility, greater mobility of the thoracic spine, a less prominent lordosis of the lumbar spine and a less prominent kyphosis in the thoracic spine in the neutral standing position. The dancers had done little or no ballet training before entering the ballet school at the age of ten. The results agree with those of earlier studies and suggest that increased flexibility is an asset for those being selected as future ballet dancers.
(-)-(3-Hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP) and transdihydrolisuride (terguride, TDHL) are partial dopamine D2 receptor agonists displaying low intrinsic activity at normosensitive postsynaptic dopamine D2 receptors in brain while activating prolactin-regulating dopamine D2 receptors in male rats with an efficacy close to that of full dopamine D2 receptor agonists. In the present study we examined the effects of these partial dopamine D2 receptor agonists on prolactin release in vitro. For this purpose prolactin-producing tumour cells which have been transfected with the dopamine D2 receptor cDNA and hence which express a dopamine D2 receptor (short isoform) that is functionally active with respect to inhibition of adenylate cyclase and prolactin release (GH4ZR7; Albert et al., J. Biol. Chem. (1990) 265, 2098) were used. While the full dopamine D2 receptor agonists, quinpirole, (+)-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) and dopamine induced a dose-dependent suppression of vasoactive intestinal peptide (VIP)-induced prolactin release from GH4ZR7, both (-)-3-PPP and terguride were inactive. Furthermore, the prolactin-suppressive effects of dopamine and quinpirole were significantly antagonized by pretreatment with (-)-3-PPP and terguride. It is concluded that partial dopamine D2 receptor agonists, which activate male lactotroph dopamine D2 receptors in vivo, may antagonize dopamine D2 receptors on GH4ZR7 cells. There were similar results from an experiment using monolayers of anterior pituitary cells from male rats. Thus, in this in vitro preparation (+)-3-PPP suppressed spontaneous prolactin release while (-)-3-PPP again was inactive.(ABSTRACT TRUNCATED AT 250 WORDS)
Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.
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OBJECTIVE: To study the pathogenicity of simian immunodeficiency virus (SIVsm) in cynomolgus monkeys in order to establish an animal model for human AIDS. METHODS: Thirty-three cynomolgus monkeys were monitored for more than 2 years following experimental infection with SIVsm. RESULTS: All the macaques became SIV-infected, as demonstrated by virus recovery from peripheral blood lymphocytes and by the appearance of viral antibodies. SIVsm was found to be pathogenic, killing 29 out of the 33 monkeys (88%) within 26 months. Clinically, infected monkeys developed lymphadenopathy, splenomegaly, diarrhoea, weight loss, neurological symptoms and a remarkably high incidence (39%) of malignant lymphomas. All lymphomas were high-grade malignant and of B-cell origin. Disease progression was associated with low CD4+ lymphocyte count, involution of initially hyperplastic follicular B-cell areas in lymph nodes, reappearance of viral antigen in serum, loss of anti-Gag antibodies and development of systemic giant cell disease in 55% of the monkeys. CONCLUSIONS: There are many similarities between SIVsm-induced AIDS in cynomolgus monkeys and human AIDS with regard to clinical, virological, immunological and pathological manifestations.
To elucidate the function of insulin-like growth factor-II (IGF-II) in the choroid plexus, the gene expression and receptor binding of IGF-II were studied in isolated epithelial cells from the porcine choroid plexus. The choroid plexus expressed multiple IGF-II transcripts of 1.2, 1.6, 2.4, and 4.4 kb, at levels higher than those found in porcine liver and kidney. These data suggest that IGF-II is synthesized by the choroid plexus. Choroid plexus epithelial cells contained high levels of IGF-I receptors on the cell surface whereas very low levels of receptor binding were found for 125I-IGF-II and 125I-insulin. Solubilization of epithelial cells showed that a large proportion of the IGF-I receptors were present in the detergent-insoluble fraction whereas IGF-II receptors and insulin receptors were concentrated in the detergent-soluble fraction. These results suggest that IGF-I receptors are located in clathrin-coated pits of the plasma membrane whereas IGF-II receptors and insulin receptors are present in endosomal vesicles. The tyrosine kinase activity of the IGF-I receptor beta-subunit was stimulated by IGF-I, IGF-II, and insulin, in order of potency, suggesting that these peptides exert a regulatory function in the choroid plexus epithelium. In conclusion, we propose that the IGF-I receptor tyrosine kinase on the surface of the epithelial cells in the pig choroid plexus mediates effects of IGF-I and IGF-II, whereas IGF-II receptors are down-regulated due to the synthesis and secretion of IGF-II in these cells.
Recent advances in magnetic resonance imaging have made it possible to visualize and quantify flow of cerebrospinal fluid (CSF) in the brain. The net flow of CSF through the cerebral aqueduct was used to measure CSF production in six normal volunteers at different times during a 24-h period. CSF production varied greatly both intra- and interindividually. The average CSF production in each time interval showed a clear tendency to circadian variation, with a minimum production 30% of maximum values (12 +/- 7 ml/h) approximately 1800 h and a nightly peak production approximately 0200 h of 42 +/- 2 ml/h. The total CSF production during the whole 24-h period, calculated as an average of all measurements, was 650 ml for the whole group and 630 ml for repeated measurements in each time interval in one of the volunteers.
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Using the choroid plexus from pig a method has been developed to purify the epithelial cells from the underlying vascularized connective tissue stroma. An epithelial cell fraction was obtained that showed a purity of at least 95%, as determined by light microscopic analysis. The epithelial cells were investigated for the presence of binding sites for the neurotransmitter peptide, vasoactive intestinal polypeptide (VIP). Suspensions of epithelial cells were found to have high affinity binding sites for 125I-labelled VIP, with maximum binding obtained after 30 min incubation at 20 degrees C with a concentration of 50 micrograms cell protein per sample. Competition experiments with displacement of [125I]VIP binding by increasing concentrations of unlabeled VIP indicated the presence of a single class of binding sites with a Kd of 3 nM and a binding capacity of 970 pmol/g cell protein. Cross-linking of [125I]VIP to epithelial cells with disuccinimido dithiobis (propionate) (DSP), followed by SDS-polyacrylamide gel electrophoresis, demonstrated binding to a single 55 kD protein. The receptor was highly specific for VIP as binding was only inhibited in the presence of high concentrations of the related peptides helodermin, growth hormone-releasing factor, secretin, and peptide histidine isoleucine. This is the first demonstration of VIP-binding to choroid plexus epithelial cells.
Using laser-Doppler flowmetry during ventriculocisternal perfusion with inulin-[14C]carboxylic acid, choroid plexus blood flow (CPBF) and CSF production were measured simultaneously in rats during periods of 3 h. Blood flow and CSF production decreased only slightly during control experiments. The effect of vasoactive intestinal polypeptide (VIP) was studied at different concentrations of the peptide given either intraventricularly or intravenously. Intraventricular administration of VIP (10(-9) or 10(-7) M) resulted in a decrease in CSF production of up to 30%, while CPBF increased by 20%, also demonstrating that CSF production and blood flow are not directly coupled in the choroid plexus. When infused intravenously, VIP (10 or 100 pmol/kg/min) increased CPBF, an effect partly antagonized at higher concentrations owing to a VIP-induced systemic hypotension. No effect of VIP on CSF production could be seen with intravenous administration.
The neurotransmitter peptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and neuropeptide Y (NPY) are located in nerve fibers supplying the pig choroid plexus, which receives an abundant sympathetic innervation. We characterized the release of [3H]noradrenaline ([3H]NA) from this tissue elicited by electrical field stimulation and studied the effects of the above-mentioned peptides on this release. The release of [3H]NA was found to be almost exclusively of neurogenic origin, despite there being a marked non-neuronal uptake of [3H]NA into the epithelium of the choroid plexus. NPY significantly decreased the release of [3H]NA by approximately 10% while VIP and PHI enhanced release by up to 25 and 35%, respectively, indicating a possible synergistic role of the two latter peptides and NA in the choroid plexus.
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Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.
The transport of thyroxine from the bloodstream to the brain and the synthesis and secretion of transthyretin (formerly called prealbumin) were studied in rats and in sheep choroid plexus perfused in vitro. Rat choroid plexus contained 4.4 micrograms and rat liver 0.39 micrograms transthyretin mRNA per gram wet tissue. The specific radioactivity of transthyretin isolated from cerebrospinal fluid of rats 60 min after intravenous injection of [14C]leucine was greater than 50 times that of transthyretin from serum. After adding [14C]leucine to the perfusion medium of an in vitro perfused sheep choroid plexus, highly radioactive transthyretin was isolated from freshly secreted cerebrospinal fluid collected from the exposed choroid plexus surface. Secretion of newly synthesized transthyretin into the perfusion medium could not be demonstrated. After intravenous injection of [125I]-thyroxine into rats, a maximum in the curve of radioactivity in tissue plotted against time after injection was observed first for choroid plexus, thereafter for cerebrospinal fluid, and still later for cortex and striatum. Based on the obtained data, a hypothesis is derived for the mechanism of the transport of thyroid hormones from the bloodstream to the brain involving transthyretin synthesized in choroid plexus and secreted into the cerebrospinal fluid.
In a random screening of camel diseases in Somalia dust-laden macrophages in lungs and/or bronchial lymph nodes were discovered in 94 of 134 animals. In 44 cases the dust-laden macrophages occurred in a number of small or large aggregates. There was a significant positive correlation between dust-laden macrophage aggregates in the lungs and pulmonary fibrosis not related to other chronic lung diseases, such as echinococcosis and chronic pneumonia. Six cases showed a cellular reaction and hyalinized nodules of the classic silicotic type. Energy dispersive X-ray analysis of the dust particles revealed presence of silica, aluminium, potassium and iron in that order. The possible clinical significance as well as the comparative pathology of the observations is discussed.