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At least 487 records · Page 27Linked to original sources
PubMed1998

Putative myeloma precursor cells expressing 2,6 sialic acid-modified antigens actually belong to the erythroid lineage.

The Golgi enzyme alpha2,6-sialyltransferase modifies glycoconjugates by adding sialic acid. In lymphocytes, different epitopes that result from this modification have been identified by the B cell-related CDw75, CDw76, HB4 or HB6 Ab. We previously described positive staining with these Ab of a highly transferrin receptor-positive (CD71) cell type in the bone marrow of multiple myeloma patients. These cells were distinct from plasma cells, but did contain Ig of the same isotype and idiotype as seen in the plasma cells. We postulated a precursor role for this cell type in myeloma. Here, we report that this CD71+ (HB4/HB6/CDw75/CDw76)+ cell is an erythroid precursor cell instead. RT-PCR did not detect Ig mRNA, and from immuno electron microscopy Ig appeared to be endocytosed rather than synthesized by these cells. At their cell surface the erythroid/megakaryocytic markers CD36 and CD41, and the erythroid-specific glycophorin A can be detected, while haemoglobin can be detected antigenically in the cytoplasm. Finally, purified cells proliferate in vitro upon addition of erythropoietin. Uptake of Ig could be explained by the presence of Fc gammaRIII(CD16), which has also been found on other haematopoietic precursor cells.

Antigens, CD↗
PubMed2001

Neuropsychological effects of low mercury vapor exposure in chloralkali workers.

Neuropsychological effects were examined in 47 mercury vapor exposed male chloralkali workers with current low concentrations of urinary mercury (mean U-Hg 5.9 nmol/mmol creatinine (Cr)). Their average duration of exposure was 13.3 years, and the calculated mean concentration of U-Hg was 9.0 nmol Hg/mmol Cr per year (exposure intensity) during their time of exposure. They were compared with 47 age-matched male referents in a cross-sectional study. The two groups were not statistically significantly different with respect to neuropsychological test performance or number of self-reported subjective symptoms. The test results of the Static Steadiness Test, which assesses tremor, were not associated with exposure to mercury vapor. However current smokers had more hand tremor than non-smokers. Statistically significant associations were found between indices of current exposure (the concentration of inorganic mercury in whole blood) and the results of the WAIS Digit Symbol Test and the Benton Visual Retention Test (number of correct responses). This could indicate a small effect of current exposure on visuomotor/psychomotor speed and attention, and immediate visual memory. Whether the association found between the historical exposure intensity and the Digit Symbol Test results may represent long-term consequences of exposure cannot be determined in this study.

Adult↗
PubMed1999

Fluorescence in situ hybridization analysis shows the frequent occurrence of 14q32.3 rearrangements with involvement of immunoglobulin switch regions in myeloma cell lines.

In many B-cell malignancies, 14q32.3 chromosomal rearrangements involving the immunoglobulin heavy chain (IgH) locus have been shown to be pathognomonic for the disease. Although in myeloma heterogeneous and complex karyotypes are found, 14q32.3 translocations are prominent. However, owing to the telomeric position of the IgH locus, 14q32.3 translocations may be easily missed. We established fluorescence in situ hybridization (FISH) assays on chromosomes and DNA fibers to determine both the occurrence of 14q32.3 rearrangements in myeloma cell lines and the precise localization of the breakpoints in the IgH locus. Our results show that 14q32.3 chromosomal rearrangements are present in almost every myeloma cell line analyzed (17 of 19, 89%). Breakpoint analysis of the lines harboring one or more 14q32.3 rearrangements with the use of fiber-FISH revealed the involvement of switch regions in the IgH locus in 11 of 17 cell lines. Remarkably, pseudogamma genes without switch regions were involved in 3 of 17 cell lines, all derived from IgA myelomas. Three of 17 cell lines contained breakpoints outside a switch or immunoglobulin heavy chain constant region. The almost ubiquitous presence of 14q32.3 rearrangements suggests an obligatory role in the development of myeloma. The high incidence of breakpoints involving switch regions indicates an oncogenic event in a late stage of B-cell differentiation.

Chromosome Aberrations↗
PubMed2001

The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus.

Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.

Amygdala↗
PubMed2001

Genomic structure and promoter characterization of an imprinted tumor suppressor gene ARHI.

We have recently identified a maternally imprinted tumor suppressor gene, ARHI (aplysia ras homolog I), the expression of which is lost in ovarian and breast cancers. We have now characterized the genomic structure of the gene including its promoter and the methylation status of its upstream CpG islands. The ARHI gene spans approximately 8 kb containing two exons and one intron. Exon 1 contains 81 non-translated nucleotides, connected to exon 2 with a 3.2-kb intron. The entire protein-coding region is located within exon 2 and encodes a 229-residue small GTP-binding protein belonging to the Ras superfamily. Genomic structure analysis has identified three potential CpG islands. Two of them (CpG island I and II) are located within the promoter and adjacent exon 1 of the ARHI gene. Aberrant methylation of these CpG islands has been detected in breast cancer cells but not in normal epithelial cells, supporting the possibility that appropriate methylation status of the CpG islands in the promoter region may play a role in the downregulation of ARHI gene expression. A TATA box is found 27 bp upstream of the transcription start site associated with several putative transcription factor binding sites. Transient transfection with nested deletion constructs of the 2-kb ARHI promoter regions fused to a luciferase reporter indicated a 121-bp sequence upstream of the transcription initiation site is required for basal promoter activity. Interestingly, this is the region where lower promoter activity has been observed in cancer cells than in normal cells.

Amino Acid Sequence↗
PubMed2002

Role of deoxycytidine kinase (dCK) activity in gemcitabine's radioenhancement in mice and human cell lines in vitro.

BACKGROUND: Gemcitabine (dFdC, 2',2'-difluorodeoxycytidine) is a deoxycytidine nucleoside analog which has a marked effect on several enzymes involved in DNA synthesis and repair. Gemcitabine has been tested as a radiosensitizer in various biological models, and radiation dose modification factors (DMF) have been reported in the range between 1.1 and 2.4. Gemcitabine is a prodrug that requires intracellular activation by phosphorylation into its active triphosphate dFdCTP form. Deoxycytidine kinase (dCK) is the enzyme involved in the first phosphorylation cascade, and several observations have suggested that dCK was a limiting factor for the cytotoxic activity of gemcitabine. OBJECTIVE: In the present article, we investigated the relationship between dCK activity and gemcitabine's radiosensitization in four mice and two human cell lines. MATERIALS AND METHODS: Four mice and two human tumor cell lines were investigated. Radiosensitization was assessed on confluent cell incubated with 5 microM gemcitabine for 3 h prior to a single radiation dose. Enzymatic activity was assessed using deoxycytidine as substrate with (specific activity) or without (total activity) inhibition of thymidine kinase 2 activity. dCK protein level was assessed by immunoblotting using a rabbit anti-human dCK antibody. mRNA expression was assessed with Northern blot using beta-actin as internal control. RESULTS: Gemcitabine's radiosensitization was heterogeneous with DMF ranging from 0.8 to 1.5. A good correlation was observed between the specific dCK activity and the protein level or the mRNA expression indicating that in our cell systems no post-transcriptional or post-translational activation occurred. An excellent correlation (r = 0.99) was observed between the specific enzymatic activity and gemcitabine's radiosensitization. Cell lines that expressed a high enzymatic activity were the more radiosensitized by gemcitabine. This correlation holds when radiosensitization was plotted against the dCK mRNA expression and protein level. CONCLUSIONS: The present study has suggested the role of dCK activity in gemcitabine's radioenhancement in human and mice cell lines. The study suggests that determination of the enzymatic activity prior to a concurrent gemcitabine and radiotherapy treatment might represent a good predictive assay for tumor response. Such concept should deserve further testing in pre-clinical and clinical settings.

Animals↗
PubMed2003

In vivo colocalization of 2-nitroimidazole EF5 fluorescence intensity and electron paramagnetic resonance oximetry in mouse tumors.

BACKGROUND AND PURPOSE: The primary objective of this study was to establish in vivo the relationship between 2-2-nitro-1H-imidazol-1yl-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) adduct formation and intratumoral oxygen concentrations measured by electron paramagnetic resonance (EPR) in a tumor model mimicking a clinical situation. The secondary objective was an attempt to calibrate in situ the immunofluorescence (IF) signal with EPR oximetry. MATERIALS AND METHODS: IM syngeneic fibrosarcoma (NFSA) bearing C3H mice were used. Three days after injection of a paramagnetic charcoal into the tumor, the mice were anesthetized, injected with the hypoxic marker EF5, and monitored every 20 min for 3 h with a low-frequency EPR spectrometer. Animals were allowed to breath either under 21 or 100% O(2). Tumors were then harvested, frozen, cut into sections including the charcoal and processed for EF5 adducts detection using monoclonal antibodies. Slices were viewed with a fluorescence microscope and 190x140 micrometer areas surrounding the charcoal were digitized and analyzed with the NIH-Image and Adobe Photoshop software. The fluorescence intensity (FI) was measured in the whole pictures and in strips of 10 micrometer around the charcoal. RESULTS: EF5 binding increased with decreasing pO(2), most substantially at pO(2) below 5 mm Hg. Baseline (ambient air) pO(2) reached 3.2+/-2.1 mm Hg in NFSA tumors. It increased to 9.8+/-3.2 mm Hg under 100% O(2). A statistically significant correlation was observed on an individual tumor basis between the FI in the first 10 micrometer strip around the charcoal and the pO(2) determined by EPR oximetry (Wilcoxon signed rank test: P<0.001). CONCLUSIONS: The present study confirms the intrinsic relationship between EF5 adduct binding and intratumoral pO(2) in an in vivo environment under biologically-relevant pO(2) values of less than 10 mm Hg.

Algorithms↗
PubMed1993

[Horton's disease disclosed by involvement of the lower limbs].

We report the case of a 62-year old woman hospitalized for acute ischaemia of the right lower limb, caused by stenosis of the superficial femoral artery associated with thrombosis of the deep femoral artery. Thromboendarterectomy was performed, and histology of the operative specimen showed thickening of the media with clusters of giant cells and fragmentation of the internal elastic lamina, without atheroma. The diagnostic of giant cell arteritis was then considered and confirmed by the presence of headaches, 38 degrees C fever and inflammatory syndrome with ESR at 75 mm in the first hour. On the other hand, biopsy of a temporal artery was negative. Corticosteroid therapy was prescribed and gave excellent clinical, laboratory and arteriographic results. It has now been demonstrated that the arteries of the lower limbs may be involved in Horton's giant cell arteritis, which is often overlooked. This involvement is rare and exceptionally proven at histology. Clinically, the most frequently described form is one of pseudo-arteritis with claudication, but a few cases of gangrene have been reported. Withdrawal of corticosteroid might be a facilitating factor. As in our patient, the arteriographic lesions are often segmental, multifocal and symmetrical, predominant in the superficial femoral artery and the arteries of the legs. The lesions regress under corticosteroid therapy, and surgery can usually be avoided. Anticoagulants are commonly prescribed when the large vessels are involved. When surgery is not indicated the diagnosis can be confirmed by biopsy of the temporal artery, which is positive in the majority of cases.

Acute Disease↗
PubMed1999

[Secondary aortoduodenal fistulas: report of 7 cases].

PURPOSE: Aortoduodenal fistulas are the most frequent aortoenteric fistulas. They may be primary (occurring after aneurysms of the native aorta) or secondary (occurring after aortic prosthesis). Aortoduodenal fistulas are a rare complication of aortic prostheses. They may be caused by prosthesis infection or due to inadequate prosthesis. METHODS: We report seven observations that emphasize issues pertaining to either diagnosis or therapy. RESULTS: The delay of occurrence is variable, with a mean of 3 years as reported in the literature. Clinical picture includes upper digestive tract hemorrhage, sometimes fever, abdominal pain or mass. Though difficult, diagnosis can be achieved through gastric endoscopy or CT-scan. Additional diagnostic procedures are often not useful and should not be numerous. Surgical procedures help guide the diagnosis and constitute the main part of the treatment with suture of the duodenum and vascular prosthesis. According to previous works, our observations including prolonged follow-up of the patients suggest that the best vascular treatment is extra-anatomic axillo-bifemoral bypass, while simple suture and prosthesis replacement lead to poor results. CONCLUSION: Mortality related to aortodigestive fistulas is high (five out of seven patients in the present study) and requires prevention, including more particularly delicate surgery and antibiotic therapy in case of any episode of infection. Aortoduodenal fistulas must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained fever.

Aged↗
PubMed1998

Use of the fixed mandibular implant in oral cancer patients: a retrospective study.

PURPOSE: A retrospective review of the fixed mandibular implant (FMI) in oral cancer patients is presented. Success of the device and associated complications are discussed. PATIENTS AND METHODS: Eighteen oral cancer patients with an FMI were identified. All were treated at a single institution. Information was obtained from medical records, radiographs, and recall examination. Demographic data, surgical history, prosthesis design, and functional data were analyzed. Results were statistically compared with outcome data for the FMI in noncancer controls. RESULTS: The average patient age was 64 years. Seventeen of the 18 patients had squamous cell carcinoma, most being T3 or T4 lesions at diagnosis. Four of 18 patients received radiation therapy (XRT) followed by resection, 11 had resection followed by XRT, two had XRT alone, and one had surgery alone. The average XRT dose to the mandible was 65.4 Gy. Two of the patients received hyperbaric oxygen (HBO). Sixteen of the implants had been loaded and followed an average of 16.4 months. Early complications included soft tissue overgrowth around pins (4 of 18); tongue ulceration (2 of 18), and intraoral wound dehiscence (2 of 18). Late complications included fistula formation (3 of 18); submental erythema (2 of 18), and persistent tissue overgrowth around pins (1 of 19). No complications required removal of the implant. Only the rate of fistula formation was statistically greater than in controls (P = .005). Average time between FMI placement and prosthesis delivery was 3.6 months. Fourteen of the 16 patients with a prosthesis reported improved ability to eat solid foods and improved articulation. All 16 patients reported improved aesthetics and increased comfort in social settings. CONCLUSIONS: The FMI is a valuable device for dental rehabilitation in oral cancer patients. Success was shown in radiated patients. The complication rate is acceptable, and stability was shown over the follow-up period. Rapid rehabilitation and functional and aesthetic improvements were also reported.

Aged↗
PubMed2001

Masking of antioxidant capacity by the interaction of flavonoids with protein.

The effect of antioxidants is often executed in complex biological mixtures where various interactions may take place. Therefore, the antioxidant capacity of antioxidants in blood plasma is examined. The assay used is the trolox equivalent antioxidant capacity (TEAC). This method gives the antioxidant capacity of a compound by measuring spectrophotometrically the disappearance of the blue/green stable ABTS [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] radical, caused by scavenging. The results show that the antioxidant capacity of quercetin, rutin, catechin or 7-monohydroxyethylrutoside (monoHER) and blood plasma is not additive. This is partly due to interactions between the antioxidant and plasma proteins. However, the antioxidant capacity of alpha-tocopherol, which also binds to protein, is not affected by the interaction. This means that besides the antioxidant capacity of the compound itself, the environment in which the antioxidant has to execute his function is important.

Antioxidants↗
PubMed1997

Changes in neuroreceptor function of tracheal smooth muscle following acute ozone exposure of guinea pigs.

We studied the effect of in vivo ozone inhalation (3 ppm, 2 h) on neuroreceptor function in guinea pig tracheal smooth muscle in vitro and the role of the epithelial layer in this process. Changes in smooth muscle tension after stimulation of the muscarinic- and beta-adrenergic receptor were recorded isometrically and stained tracheal tissue sections were histologically evaluated for changes in the epithelial and smooth muscle layer. Ozone exposure resulted in an increase in maximal contraction following stimulation of the muscarinic receptor, whereas pD2 values remained unchanged. After stimulation of the beta-adrenergic receptor no increase in maximal relaxation but only an increase in pD2 value was observed after correction for differences in precontraction level in control- and ozone-exposed situations. Mechanical removal of the epithelial layer resulted in a slight increase of the maximal contraction level after stimulation with methacholine in the control situation, whereas exposure to ozone resulted in a strong decrease of the maximal contraction level under these conditions. Histological stainings showed a slight and focal influx of neutrophilic granulocytes in the epithelial layer, submucosal layer and airway lumen after exposure to ozone. These data support the idea that ozone is able to increase the maximal degree of airway narrowing upon muscarinergic stimulation, i.e. a hyperreactivity response. The results also suggest that functionally altered epithelium plays an important role in the process of ozone-induced hyperreactivity, possibly linked with an early inflammatory response.

Animals↗
PubMed2003

Hippocampal modulation of sensorimotor processes.

While the hippocampus makes unique contributions to memory, it has also long been associated with sensorimotor processes, i.e. innate processes involving control of motor responses to sensory stimuli. Moreover, hippocampal dysfunction has been implicated in neuropsychiatric diseases, such as schizophrenia and anxiety disorders, primarily characterized by non-mnemonic deficits in the processing of and responding to sensory information. This review is concerned with the hippocampal modulation of three sensorimotor processes in rats-locomotor activity, prepulse inhibition (PPI) of the startle reflex, and the startle reflex itself-whose alterations are related to human psychosis or anxiety disorders. Its main purpose is to present and discuss the picture emerging from studies examining the effects of pharmacological manipulations of the dorsal and ventral hippocampus by local drug microinfusions. While a role of the hippocampus in regulating locomotor activity, PPI, and startle reactivity has also been suggested based on the effects of hippocampal lesions, the microinfusion studies have revealed additional important details of this role and suggest modifications of notions based on lesion studies. In summary, the microinfusion studies corroborate that hippocampal mechanisms can directly influence locomotor activity, PPI, and startle reactivity, and that aberrant hippocampal function may contribute to neuropsychiatric diseases, in particular psychosis. The relation between different sensorimotor processes and hippocampal neurotransmission, the role of ventral and dorsal hippocampus, and the extrahippocampal mechanisms mediating the hippocampal modulation of different sensorimotor processes can partly be dissociated. Thus, the hippocampal modulation of these sensorimotor processes appears to reflect multiple operations, rather than one unitary operation.

Animals↗
PubMed1998

Maternal and fetal plasma concentrations of endothelin, lipidhydroperoxides, glutathione peroxidase and fibronectin in relation to abnormal umbilical artery velocimetry.

OBJECTIVE: To study plasma concentrations of endothelin (ET), lipidhydroperoxides (LOOH), glutathione peroxidase (GSHpx) and fibronectin in relation to abnormal umbilical artery velocimetry. STUDY DESIGN: Plasma concentrations of ET, LOOH, GSHpx and fibronectin were measured in fetal and maternal venous blood in: (i) a control group (n=10); (ii) in pregnancies complicated by intrauterine growth retardation (IUGR) (n=6) or preeclampsia (n=5) with positive end diastolic flow; and in (iii) pregnancies complicated by absent or reversed end diastolic (ARED) flow in the umbilical artery (n=18). All children were delivered by primary caesarean section. RESULTS: The significantly highest maternal and fetal ET concentrations were found in plasma collected in pregnancies complicated by ARED flow in the umbilical artery. Maternal fibronectin levels were significantly raised in the ARED flow group. Maternal plasma ET levels were lowest in pregnancies complicated by IUGR. The maternal and fetal plasma concentrations of LOOH and GSHpx did not differ significantly between the groups. CONCLUSION: Abnormal Doppler velocimetry, especially ARED flow is associated with elevated maternal and fetal plasma levels of ET. The exact mechanism causing the placental vasoconstriction is unknown yet, but oxidative stress seems not to be involved.

Endothelins↗
PubMed1997

The pharmacology of the antioxidant lipoic acid.

1. Lipoic acid is an example of an existing drug whose therapeutic effect has been related to its antioxidant activity. 2. Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant activity of lipoic acid is determined by its concentration and by its antioxidant properties. Four antioxidant properties of lipoic acid have been studied: its metal chelating capacity, its ability to scavenge reactive oxygen species (ROS), its ability to regenerate endogenous antioxidants and its ability to repair oxidative damage. 4. Dihydrolipoic acid (DHLA), formed by reduction of lipoic acid, has more antioxidant properties than does lipoic acid. Both DHLA and lipoic acid have metal-chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage. 5. As a metal chelator, lipoic acid was shown to provide antioxidant activity by chelating Fe2+ and Cu2+; DHLA can do so by chelating Cd2+. 6. As scavengers of ROS, lipoic acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro-oxidant activity has been observed. However, lipoic acid can act as an antioxidant against the pro-oxidant activity produced by DHLA. 7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione. 8. DHLA can provide peptide methionine sulfoxide reductase with reducing equivalents. This enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease. 9. Through the lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during oxidative stress. 10. Within drug-related antioxidant pharmacology, lipoic acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.

Animals↗