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Biomedical subjects

C Marin

Publications and source records attributed to C Marin.

At least 19 recordsLinked to original sources

ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression.

The one-hybrid system with an inverted CCAAT box as the DNA target sequence was used to identify proteins acting on key DNA sequences of the promoter of the topoisomerase IIalpha gene. Screening of cDNA libraries from the leukemia Jurkat cell line and from the adult human thymus resulted in the isolation of a novel protein of 793 amino acids (89,758 Da). This protein has in vitro CCAAT binding properties and has been called ICBP90. Adult thymus, fetal thymus, fetal liver, and bone marrow, known as active tissues in terms of cell proliferation, are the tissues richest in ICBP90 mRNA. In contrast, highly differentiated tissues and cells such as the central nervous system and peripheral leukocytes are free of ICBP90 mRNA. Western blotting experiments showed a simultaneous expression of topoisomerase IIalpha and ICBP90 in proliferating human lung fibroblasts. Simultaneous expression of both proteins has also been observed in HeLa cells, but in both proliferating and confluent cells. Overexpression of ICBP90 in COS-1-transfected cells induced an enhanced expression of endogenous topoisomerase IIalpha. Immunohistochemistry experiments showed that topoisomerase IIalpha and ICBP90 were coexpressed in proliferating areas of paraffin-embedded human appendix tissues and in high-grade breast carcinoma tissues. We have identified ICBP90, which is a novel CCAAT binding protein, and our results suggest that it may be involved in topoisomerase IIalpha expression. ICBP90 may also be useful as a new proliferation marker for cancer tissues.

Adult

Narrow beneficial effect of dextromethorphan on levodopa-induced motor response alterations in an experimental model of parkinsonism.

The effects of acute and chronic dextromethorphan on levodopa-induced motor response alterations have been studied in rats with unilateral lesion of nigrostriatal pathway induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a 6-OHDA injection (8 microg) into the left medial forebrain bundle. To validate the effect of acute dextromethorphan administration, groups of rats were treated with levodopa (25 mg/kg, twice daily) for 22 days. On day 23, animals received dextromethorphan (20, 30 or 40 mg/kg) immediately before levodopa. In a second set of experiments, lesioned rats were concomitantly treated with levodopa plus dextromethorphan (20, 30 or 40 mg/kg, twice at day) for 22 consecutive days in order to investigate the potential effect of chronic dextromethorphan administration in preventing the decrease in the duration of motor response. As expected, the duration of the motor response to levodopa had significantly decreased by the 22nd day of levodopa in each group of treatment. Acute administration of dextromethorphan on day 23 reversed the reduction in the duration of the levodopa response only when administered at the lowest dose used in the present study (20 mg/kg) (p<0.05). Chronic administration of dextromethorphan concomitant to levodopa did not prevent levodopa effect showing a significant decrease on motor response duration (124+/-4 on day 1 vs. 88+/-16 on day 22, p<0.05, 30 mg/kg, twice a day). Our results indicate that in parkinsonian rats dextromethorphan is not a useful drug to prevent levodopa-induced motor alterations, however, low doses of dextromethorphan may be beneficial to reverse these alterations in motor response.

Animals

Trace element levels in whole blood samples from residents of the city Badajoz, Spain.

Copper, lead, cadmium, and zinc were determined by anodic stripping voltammetry after sample digestion and potentiometric stripping analysis was used for Pb and Cd determination in original samples. Selenium was determined by cathodic stripping voltammetry or hydride generation AAS. Element levels found in the whole blood sample in a group of 82 people are for Cd: 0.98 +/- 0.94 ng/ml; for Pb: 46.7 +/- 28.6 ng/ml; for Cu: 1.07 +/- 0.12 micrograms/ml; for Zn: 6.95 +/- 1.08 micrograms/ml, and for Se: 116 +/- 25 ng/ml. Analytical data have been correlated to age, sex, smokers or non-smokers, drinking and food habits.

Adult

Systemic administration of NMDA and AMPA receptor antagonists reverses the neurochemical changes induced by nigrostriatal denervation in basal ganglia.

In Parkinson's disease, nigrostriatal denervation leads to an overactivity of the subthalamic nucleus and its target areas, which is responsible of the clinical manifestations of the disease. Because the subthalamic nucleus uses glutamate as neurotransmitter and is innervated by glutamatergic fibers, pharmacological blockade of glutamate transmission might be expected to restore the cascade of neurochemical changes induced by a dopaminergic denervation within the basal ganglia. To test this hypothesis, two types of glutamate antagonists, the NMDA receptor antagonist MK-801 and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist LY293558, were administered systemically, either alone or in combination with L-DOPA, in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. The effect of treatment was assessed neurochemically by analyzing at the cellular level the functional activity of basal ganglia output structures and the subthalamic nucleus using the expression levels of the mRNAs coding for glutamic acid decarboxylase and cytochrome oxidase, respectively, as molecular markers of neuronal activity. The present study shows that treatment with glutamate antagonists, and particularly with AMPA antagonists, alone or in combination with L-DOPA, reverses the overactivity of the subthalamic nucleus and its target areas induced by nigrostriatal denervation. These results furnish the neurochemical basis for the potential use of glutamate antagonists as therapeutic agents in Parkinson's disease.

Animals

Detection of 14-3-3 brain protein in the cerebrospinal fluid of patients with paraneoplastic neurological disorders

The detection of 14-3-3 protein in cerebrospinal fluid by immunoblotting is useful for the diagnosis of Creutzfeldt-Jakob disease (CJD). We found 14-3-3 protein in 10 of 80 (12.5%) patients with paraneoplastic neurological disorders (PNDs), whose presenting symptoms may mimic those of CJD. In 47 of 48 CJD patients, the 14-3-3 protein was detected as a single band, and it was detected as a double band in 1 patient. The double-band pattern was observed in 9 of the 10 14-3-3 proteinpositive patients with PNDs. The 14-3-3 protein assay may be positive in PND patients, but the immunoblotting pattern distinguishes most PND samples from those of CJD.

Journal Article

[Subareolar injection of 99m-Tc sulfur colloid for sentinel nodes identification in multifocal invasive breast cancer].

The objective were to study the relevance of the subareolar injection for sentinel node [SN] detection in multiple foci breast cancer. Seventy-nine patients with infiltrative breast carcinoma (diagnosed pre-operatively by core biopsy) and a mean age of 55 (31-78) years were enrolled. All patients were free of previous homolateral surgery, chemotherapy, locoregional radiotherapy or prevalent axillary lymph node. Using four 0.1 ml injections of 1.8 MBq, the technetium-99m 100 nm filtered sulfur colloid was injected by subareolar way (group I) in 16 cases of radiologically cancer with multiple invasive foci and 31 cases of radiologically unifocal cancer, and by peritumoral way (group II) in 32 cases of radiologically unifocal cancer. Scintigrams were obtained 2 to 4 hours after the injections and radioactive nodes were detected peroperatively 18 hours after the injection by intraoperative detection probe. Individual removal of all radioactive nodes was followed by axillary dissection at levels I and II of Berg including Rotter area control. All sentinel nodes were submitted to standard histopathological analysis on serial sections at 500 mu intervals completed by immunohistochemistry for cytokeratin on negative SN. SN were detected by scintigrams in 85% and 88% of the cases of group I and group II respectively, but in 98% and 97% of the cases of respectively both groups by intraoperative probe. Group I was composed of 69% ductal, 22% lobular and 9% tubular carcinomas, and group II of 87% ductal, 10% lobular and 3% tubular carcinomas. Seven and 5 radiologically unifocal tumors were in fact with multiple invasive foci at histology in groups I and II respectively. The complete scintigraphic procedure permitted the detection of a mean number of 2.7 (1-7) SN in group I and 2.3 (1-4) in group II (NS). In group I, the SN were metastatic in 22 patients (48%), 15 of them with the metastases being restricted to the SN, whereas in group II, the SN were metastatic in 9 patients (28%), 5 of them with the positivity restricted to the SN. No false negative result (SN negative and other axillary nodes positive) was observed in group I and only one false negative result in group II which was related to a cancer with histological multiple invasive foci. Sensitivities were 100% and 90%, and negative predictive values were 100% and 95%, for groups I and II respectively. Subareolar injection of radiocolloid allows identification of SN in cases of unifocal and multiple cancer. The mean number of SN detected by the subareolar method is not significantly different, although higher, to that detected by peritumoral injection.

Adenocarcinoma

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Adult

Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus.

Previous studies have shown that the A-IV-347Ser polymorphism is associated with the variability in low density lipoprotein (LDL)-cholesterol response to dietary therapy. The present study was designed to evaluate the association of this polymorphism with the individual variability observed in postprandial lipemic response. This polymorphism was characterized in 50 healthy male subjects homozygous for the apolipoprotein (apo)E3 allele. All subjects were subjected to a vitamin A-fat load test. Blood was drawn at time 0 and every hour over a period of 11 hours. Cholesterol and triglycerides (TG) in plasma and lipoprotein fractions of CH, TG, and retinyl palmitate (RP) were determined. Data from the postprandial lipemia revealed that subjects with the A-IV-347Ser allele (n = 14) have a lower postprandial response in total TG (P < 0.025), large triglyceride rich lipoproteins (TRL) TG (P < 0.02), and small-TRL TG levels (P < 0.007), and a higher postprandial response in large-TRL apoA-IV (P < 0.006) and apoB-100 (P < 0.041) levels than subjects homozygous for the A-IV-347Thr subjects (n = 36). In conclusion, the modifications observed in postprandial lipoprotein metabolism associated with this polymorphism within the apoA-IV gene locus may be involved in the variability in LDL-CH response observed in subjects consuming high saturated fat diets.

Adolescent

Juxtacortical chondromyxoid fibroma: imaging findings in three cases and a review of the literature.

Chondromyxoid fibroma is a rare bone neoplasm characterized by chondral, myxoid and fibrous differentiation. Uncommon locations include the bone surface. Roentgenography, MRI and ultrasound can suggest the diagnosis. However, diagnosis of chondromyxoid fibroma is rarely made prior to biopsy. We present the radiologic and pathologic findings in three patients with this tumor and a review of the literature.

Adult

Striatal synaptophysin levels are not indicative of dopaminergic supersensitivity.

Recent evidence suggests that behavioral supersensitivity to dopamine (DA) agonists observed in chronic neuroleptic-treated animals might be related to changes in synaptic morphology and density. The aim of this study was to test this hypothesis using Western blotting to determine the striatal synaptophysin levels in rats chronically treated with haloperidol followed by sub-acute administration of a DA agonist. Chronic haloperidol treatment (1 mg/kg/day for 21 days) produced an 88% increase in striatal synaptophysin levels and a 73% increase in apomorphine-induced stereotypes. Sub-acute administration of the DA D-1 receptor agonist SKF38393 (10 mg/kg/day for 5 days) or the DA D-2 receptor agonist quinpirole (1 mg/kg/day for 5 days) did not modify the haloperidol-induced increase in striatal synaptophysin levels. However, sub-acute administration of SKF38393 attenuated (62%) haloperidol-induced stereotypies. We conclude that there is no direct relationship between stereotyped behavior and synaptophysin levels indicating that striatal synaptophysin levels are not a good marker of dopaminergic supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin's disease.

We studied an autoantibody (called anti-Tr), found in the serum and CSF of five patients with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). Anti-Tr antibodies labelled the cytoplasm of Purkinje cells of human and rat cerebellum. The molecular layer of rat cerebellum showed a characteristic dotted pattern suggestive of immunoreactivity of dendritic spines of Purkinje cells. Patients with cerebellar disorders without HD (159) or HD without PCD (30) did not harbor anti-Tr antibodies. Immunoblots of human Purkinje cells or rat and mouse cerebellum were negative. Anti-Tr antibodies, as defined in this study, appear specific for HD-associated PCD. The immunohistochemical pattern described in the rat cerebellum coupled with the absence of reactivity in the immunoblot may be used to identify anti-Tr antibodies.

Adolescent

Effect of 347-serine mutation in apoprotein A-IV on plasma LDL cholesterol response to dietary fat.

Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apoprotein (apo) A-IV has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. One mutation has been described in the apo A-IV gene that causes substitution of Ser for Thr at position 347. To study the influence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr allele (347Thr) and the rest who were either homozygous (n = 2) or heterozygous carriers of the Ser allele (347Ser). They consumed three consecutive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Program (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in monounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers of the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P < .034), LDL-C (-0.62 vs -0.31 mmol/L, P < .012), and apo B (-14 vs -8 mg/dL, P < .01) levels when they were switched from the SFA to the NCEP type 1 diet than homozygous carriers of the 347Thr allele. The change from the NCEP type 1 to the MUFA diet resulted in a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P < .028) and apo B (5 vs -1 mg/dL, P < .006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the G-->A polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholesterol, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by the 347Ser mutation of apo A-IV.

Adult

Dietary fat clearance in normal subjects is modulated by genetic variation at the apolipoprotein B gene locus.

Apolipoprotein B (apo B) plays a dominant role in cholesterol homeostasis. Several polymorphic sites within or adjacent to the gene locus for apo B have been detected. The X+ allele (XbaI restriction site present) of the XbaI restriction fragment polymorphism on the apo B gene has been found in some studies to be associated with higher serum cholesterol and/or triglyceride levels and with greater dietary response. The present study was designed to evaluate whether the apo B XbaI polymorphism was associated with the interindividual variability observed during postprandial lipemia. Fifty-one healthy young male volunteers [20 X-/X- (X-), and 31 X+/X- or X+/X+ (X+)], homozygotes for the apo E3 allele, were subjected to a vitamin A-fat load test. Subjects with the X- genotype had significantly greater retinyl palmitate (RP) and apo B-48 postprandial responses on both the large and the small TRL lipoprotein fractions compared with X+ subjects. In summary, subjects with the X-/X- genotype at the apo B locus have a greater postprandial response than X+ subjects. These differences observed in postprandial lipoprotein metabolism could explain some of the reported associations of this polymorphism to coronary heart disease risk.

Adolescent