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Biomedical subjects

P Roth

Publications and source records attributed to P Roth.

At least 109 records · Page 6Linked to original sources

Macrophage colony-stimulating factor in human fetal astrocytes and microglia. Differential regulation by cytokines and lipopolysaccharide, and modulation of class II MHC on microglia.

CSF-1 is a growth factor that selectively promotes the proliferation, survival, and differentiation of cells of the mononuclear phagocyte series. As part of a study on the role of cytokine and hematopoietic growth factors in central nervous system (CNS) development and inflammation, we examined the expression of CSF-1 in dissociated glial cells cultured from human fetal CNS tissue. CSF-1 mRNA and protein were constitutively expressed by astrocytes. The steady state level of CSF-1 mRNA was markedly up-regulated by both IL-1 beta and TNF-alpha in a time- and dose-dependent manner, whereas only a minimal increase was detected after stimulation with LPS. In unstimulated astrocyte cultures, CSF-1 protein levels gradually increased to 3.5-fold base-line values by 96 h and were significantly increased by all three stimulants in the order of IL-1 > or = TNF > LPS. Low levels of CSF-1 mRNA and protein were also detected in unstimulated microglia cultures. In contrast to astrocyte cultures, CSF-1 mRNA and protein increased significantly after stimulation with LPS, but changed only minimally after exposure to TNF-alpha or IL-1 beta. The effect of CSF-1 on cell proliferation, morphology, and class II MHC Ag expression was determined in highly enriched cultures of microglia and astrocytes. Microglia treated with CSF-1 showed a modest level of proliferation and differentiation into rod-shaped cells, whereas neither cell number nor shape was changed in astrocyte cultures. Interestingly, marked inhibition of both basal and IFN gamma-induced class II MHC Ag expression was observed in microglial cells cultured in the presence of CSF-1, whereas no effect was detected in astrocytes. These results suggest the possibility that in situ production of CSF-1 in the CNS may regulate normal glial cell development and contribute to the immunologic status of the CNS through the down-regulation of class II MHC expression.

Astrocytes↗

Response to a single oral test of molybdenum stable isotopes for absorption studies in humans.

Two volunteer subjects were given orally enriched solutions of Mo-95 and Mo-96 respectively. Blood samples were drawn at various times following the tracer administration. The Mo-95 and Mo-96 content in plasma samples was determined by proton nuclear activation and the response to the single oral test of enriched stable molybdenum isotopes was determined. Assuming a simple two-open-compartment model where the first compartment is the gastrointestinal tract and the other is the plasma, an indicative value of the fractional intestinal absorption for the two subjects is given. The feasibility of direct quantitative measurements of Mo intestinal absorption by the double-tracer technique, using stable tracers, is evidenced.

Administration, Oral↗

Microsurgical anatomy of the hippocampal arteries.

An anatomical study of the vascularization of the hippocampus was performed on 30 hemispheres. There were a total of 140 arteries supplying the hippocampi, for an average of 4.7 arteries per hemisphere (range three to seven arteries). Based on the origin and caliber of the arteries supplying the hippocampus, the hemispheres were divided into five groups: A) in 57% of the hemispheres studied, the origin was mixed and included the anterior choroidal artery (AChA), the main trunk of the posterior cerebral artery (PCA), and the inferior temporal, lateral posterior choroidal, and splenial branches of the PCA; B) in 27%, all of the inferior temporal branches of the PCA predominantly supplied the hippocampus; C) in 10%, the anterior inferior temporal branch of the PCA was the predominant supplier: D) in 3%, the hippocampus was predominantly supplied by arteries originating from the main trunk of the PCA (Uchimura artery); and E) in 3%, the AChA gave origin to the hippocampal vessel. It was found as a result of this study that the PCA directly and by its branches contributes much more to the blood supply of the hippocampal formation than the AChA. The uncal sulcus was found to be an important anastomotic site between the hippocampal branches of the AChA and the hippocampal branches of the PCA. In 26.6% of hemispheres, one of the hippocampal arteries arose from the lateral posterior choroidal artery. The splenial artery made a loop close to the extraventricular part of the hippocampal tail and gave off multiple vessels to this structure in 36.6% of hemispheres. The finding that the AChA passes through the choroid fissure as a trunk and its later division into the lateral plexal and medial perforating branches within the choroid plexus may be of surgical significance.

Arteries↗

[Pregnancy without medical monitoring: obstetrical and neonatal prognosis. A retrospective study of 88 cases].

Unregistered and unmonitored pregnancies account for 0.2 to 0.6 p. cent of all pregnancies. They essentially concern young, single, primiparous mothers from disadvantaged social backgrounds. Labour and delivery are generally without difficulty but the neonatal prognosis is impaired by a high proportion of premature and underdeveloped infants, often requiring a long stay in a pediatric unit.

Adolescent↗

[Ivemark syndrome: 2 case reports].

Ivemark Syndrome is a multiple organ syndrome associated with splenic abnormalities, complex cardiac pathology and an abnormality of the abdominal viscera. The incidence in our department is 1/6000 deliveries and the teratogenic effect seems to occur between the 30th and 40th days of intrauterine life, but the cause is unknown. The principal warning signal is bradycardia. Prenatal diagnosis can be made by ultrasound. The prognosis depends on the degree of malformation of the heart.

Abnormalities, Multiple↗

[Toxoplasmosis and pregnancy: is it possible to simplify the diagnostic procedures?].

About 1% of all pregnancies in France are complicated by a primary infection with toxoplasmosis. The risk for the fetus being affected increases during the pregnancy but the seriousness of the effect on the fetus becomes less with more advanced pregnancies. Treatment of the mother using Spiramycin have been proven to be efficient, lessening the risk for the fetus being affected. The diagnosis of the fetus being affected rests on a whole bundle of presumptive evidence culled from non-invasive methods and invasive methods which are not without risk. (Direct or over-enthusiastic diagnostic techniques or none at all). We have studied a series of 101 primary infections with toxoplasmosis for which we have not carried out any invasive diagnostic techniques. The long term results in 77 infants show no difference in fetal morbidity and better results as far as mortality are concerned. We therefore propose simplifying the diagnostic approach in cases of primary infection with toxoplasmosis during pregnancy.

Decision Trees↗

Tumours of the limbic and paralimbic systems.

Clinical manifestations, findings, management and outcome of a series of 177 cases with tumours of the limbic and paralimbic systems are presented. There was no operative mortality. Postoperatively 95% of them had no or only minor neurological deficits. Most of them were able to resume work. Pre-operatively 77% of the patients had epilepsy, but 84% became seizure-free after tumour removal. All 77 cases with malignant tumours died within 1-5 years. In the past many neurosurgeons were reluctant to attempt complete tumour removal in these areas. This series demonstrates the efficacy of highly skilled microneurosurgery.

Adolescent↗

Adherence of human newborn infants' monocytes to matrix-bound fibronectin.

The localization of monocytes to sites of inflammation is mediated by interactions with extracellular matrix components including fibronectin, a nonimmune opsonin with binding sites for collagen, fibrin, heparin, and cell surfaces. This study demonstrates that newborn infants' monocytes bind to both gelatin (i.e., denatured collagen) and matrix-bound fibronectin to a degree comparable to that of adult-derived cells.

Adult↗

Changes of erythropoietic and storage iron components in certain clinical situations as evaluated by ferrokinetic investigations.

A method is described for the quantitative analysis of in vivo organ measurements of 59Fe activity in ferrokinetic investigations. The time-activity curves obtained by sequential surface monitoring over sacrum, liver and spleen can be resolved quantitatively into their different components contributing to the recorded count rate. The analysis is performed in three steps: (1) Count rate contributions from activity in other organs and from scattered radiation from regions outside the organ under investigation are corrected. (2) Distinction is made between radioactivity uptake of the tissue and radioactivity contained in the perfusing blood. (3) The resulting net organ activity is then further resolved into an erythropoietic and a storage iron component by use of a computer program (SAAM-27) and assuming a compartmental model for internal iron exchange. The method was tested in three groups of patients with different haematological disorders and in normal controls. Characteristic patterns of the parameters are found for different diseases and the results correlated well with the clinical findings. It is concluded that in vivo organ measurements of 59Fe activity, when performed and analysed with sufficient care, can provide an insight into the dynamics of the iron exchange that is taking place in an organ. This analytical approach may improve the diagnostic predictions of ferrokinetic investigations.

Erythropoietin↗

Effect of recombinant human erythropoietin on iron balance in maintenance hemodialysis: theoretical considerations, clinical experience and consequences.

Iron deficiency is the main reason for insufficient response to rEPO therapy. Serum ferritin and transferrin saturation give valuable information on storage iron and iron transport. Iron demand for correction of anemia can easily be estimated after HCT (vol%) x average blood volume (dl) = mg iron. Inadequate iron supply of the bone marrow in the presence of sufficient storage iron in the RES develops frequently under rEPO, possibly explaining the improvement of bone marrow response to rEPO by concomitant intravenous iron supply. The reasons of functional iron deficiency are still speculative.

Anemia↗

Induction of monocytic cell adherence to matrix-bound fibronectin by phorbol ester.

The inflammatory response requires the localization of monocytic cells to sites of tissue injury through adherence to extracellular matrix molecules such as fibronectin (Fn), a nonimmune opsonin, which binds to collagen, fibrin, heparin and cell surfaces. Adherence to this molecule of two myeloid cell lines differing in their stage of differentiation, was studied. In the baseline state, U937 monocytic cells bound specifically to matrix-bound Fn, while HL-60 promyelocytic cells bound minimally. Exposure to Phorbol myristate acetate (PMA) dramatically increased binding of both U937 and HL-60 cells to Fn with plateau effects at 10 ng/ml for both cell lines and at 30 and 60 minutes for U937 and HL-60, respectively. Treatment with metabolic inhibitors suggests that PMA stimulation depends at least in part on intact energy metabolism, protein synthesis and cytoskeletal components. This system should help elucidate the early molecular and biochemical events involved in monocyte adherence to the extracellular matrix.

Cell Adhesion↗

Factors affecting the rearrangement efficiency of an Ig test gene.

A rearrangement test gene, pHRD, containing the mouse IgH enhancer and the metallothionein promoter, has previously been shown to rearrange efficiently after transfection into a pre-B cell line. Experiments are now reported that assess the requirements of the DNA substrate as well as of the transfected cells for efficient rearrangement. It was found that deletion of the metallothionein promoter or substitution of the IgH enhancer by the kappa enhancer did not affect rearrangement. However, deletion of the Ig enhancer reduced the efficiency. Transfection of pHRD into stable hybrids of pre-B cells and myeloma cells resulted in a high frequency of rearrangement only if certain myeloma chromosomes were lost. Furthermore, pHRD introduced into rearrangement incompetent myeloma cells upon subsequent cell fusion with pre-B cells was rearranged only very rarely and then apparently only immediately after cell fusion. Stable pre-B cell x myeloma hybrids that retained the critical myeloma chromosomes were found to have lost VDJ recombinase activity and transcripts of the RAG-1, RAG-2 and TdT genes. It is concluded that transcription, i.e., the copying of the DNA by polymerase, is probably not required for rearrangement, but that the rearrangement substrate must be in an "open" chromatin state, such as may be provided by transcriptional factors. Furthermore, the absence of rearrangement in myeloma cells is apparently due to the continued action of an inhibitor of rearrangement.

Animals↗

Intracranial venous hypertension and the effects of venous outflow obstruction in a rat model of arteriovenous fistula.

A model of rat arteriovenous fistula (AVF) was created using a proximal common carotid artery to distal external jugular vein anastomosis. Anatomical dissections revealed that the external jugular vein is the primary vessel draining intracranial venous blood. Physiological measurements were made with the AVF open and closed, and during venous outflow occlusion of the contralateral external jugular vein. Opening the AVF increased torcular pressure from 6.5 +/- 0.6 to 13.5 +/- 1.1 mm Hg and decreased mean arterial pressure from 82.7 +/- 1.8 to 62.8 +/- 1.8 mm Hg (both P less than .05), decreasing cerebral perfusion pressure from 76.2 +/- 1.7 to 49.3 +/- 2.2 mm Hg (P less than .05). Middle cerebral artery blood flow velocity (MCA BFV) decreased from 6.8 +/- 1.1 to 4.2 +/- 0.7 cm/s (P less than 0.05). In rats with an AVF, occlusion of venous outflow increased torcular pressure to 34.8 +/- 3.1 mm Hg (P less than 0.05), MCA BFV decreased to 1.8 +/- 0.5 cm/s (P less than 0.05), and severe ischemic changes were seen on the electroencephalogram. Under this condition, torcular pressure and systemic arterial pressure had a positive linear relationship (P less than 0.05), whereas in control rats torcular pressure and arterial pressure had no relationship. Restoration of cerebral perfusion pressure by release of venous outflow occlusion and AVF closure transiently increased MCA BFV to 69% above baseline (P less than 0.05). Histological examination 1 week after permanent venous outflow occlusion revealed venous infarction, subarachnoid hemorrhage, and severe brain edema in rats with an AVF but not in control rats without an AVF. This model of cerebrovascular steal with venous hypertension reproduces both hemodynamic and hemorrhagic complications of human AVF and emphasizes the importance of venous outflow obstruction and venous hypertension in the pathophysiology of these lesions.

Animals↗