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1.
Carbohydr Polym ; 212: 260-269, 2019 May 15.
Article in English | MEDLINE | ID: mdl-30832856

ABSTRACT

Glucoamylolysis of maize starch at 55 °C has been studied by means of scanning electron microscopy (SEM), wide-angle X-ray diffraction spectroscopy (WAXD), and differential scanning calorimetry (DSC). It was found that hydrolysis is accompanied by changes in thermodynamic parameters of diluted aqueous dispersions of partially hydrolyzed starches. Such changes are ensured by two processes directly from hydrolysis and accompanying annealing. At relatively low degrees of hydrolysis (less than 30%), changes in thermodynamic parameters are mainly controlled by annealing. At the same time, at high degrees of hydrolysis (more than 40%), the main contribution to changes in thermodynamic parameters of partially hydrolyzed starch granules is due to the hydrolysis itself. It has been established that the main controlling parameter is the thickness of crystalline lamellae Lcrl, which, when annealed, increases, but tends to decrease at deeper glucoamylolisis. It has been established that the thickness Lcrl of crystalline lamellae, which increases with annealing, but shows a tendency to decrease with deeper glucoamylolysis is the most representative parameter of changes in maize starch after hydrolysis.


Subject(s)
Glucan 1,4-alpha-Glucosidase/chemistry , Glucan 1,4-alpha-Glucosidase/metabolism , Starch/chemistry , Starch/metabolism , Thermodynamics , Zea mays , Chemical Phenomena , Hydrolysis , Starch/isolation & purification , X-Ray Diffraction/methods
2.
Dokl Biochem Biophys ; 480(1): 146-148, 2018 May.
Article in English | MEDLINE | ID: mdl-30008096

ABSTRACT

For the first time, with the aid of differential scanning calorimetry, the thermal denaturation of fibrinogen under induced oxidation was studied. All fibrinogen structural elements detected by DSC (D region, αC-domain, and E region) are subjected to oxidation. Structural changes in fibrinogen molecule were characterized by the denaturation temperature, denaturation enthalpy, and van't Hoff enthalpy.


Subject(s)
Fibrinogen/chemistry , Protein Processing, Post-Translational , Calorimetry, Differential Scanning/methods , Humans , Oxidation-Reduction , Protein Domains
3.
Article in Russian | MEDLINE | ID: mdl-29560941

ABSTRACT

AIM: To study the phenomena of visual-hemispatial neglect in healthy people and patients with brain diseases of different genesis. MATERIAL AND METHODS: Eighty-eight patients with schizophrenia spectrum disorders, 68 patients with exogenous organic brain diseases and 240 healthy adults of different age were included in the study. The digit cancellation test modified by the authors was used. RESULTS AND CONCLUSION: The validity of the modified digit cancellation test was approved and its age standards were obtained. In healthy right-handed people, there was the bias of attention focus to the left, the decrease of asymmetry intensity of visual-spatial inattention during physiological aging and the presence of some clinical peculiarities of neglect in schizophrenia spectrum disorders and lateralized organic damages of the brain. This variant of the test can be recommended for practical use as the sensitive psychometric tool.


Subject(s)
Perceptual Disorders , Schizophrenia , Attention , Brain , Extremities , Functional Laterality , Humans , Neuropsychological Tests
4.
Dokl Biochem Biophys ; 474(1): 231-235, 2017 May.
Article in English | MEDLINE | ID: mdl-28726091

ABSTRACT

For the first time, by using the complex of physicochemical methods (mass-spectrometry, differential scanning calorimetry, spectrofluorimetry, method of spectral and fluorescent probes, dynamic light scattering, and UV spectrophotometry), the oxidation-mediated modification of chemical and spatial structure of albumin has been studied. All albumin structural regions are subjected to oxidation, methionine and aromatic amino acids primarily involved in oxidation. The albumin melting shows a decrease in thermal stabilization of the structure and changing of aggregation upon oxidation. The change in physical and chemical properties of albumin under different quantity of the oxidizer has been analyzed.


Subject(s)
Serum Albumin/metabolism , Amino Acid Sequence , Humans , Models, Molecular , Oxidation-Reduction , Ozone/metabolism , Protein Structure, Secondary , Serum Albumin/chemistry
5.
Zh Nevrol Psikhiatr Im S S Korsakova ; 115(1 Pt 2): 13-19, 2015.
Article in Russian | MEDLINE | ID: mdl-25909801

ABSTRACT

OBJECTIVE: A complex neuropsychological and neuroimaging study of deep brain structures in depression with cognitive impairment. MATERIAL AND METHODS: We studied 73 patients with endogenous depression and 86 patients with depressive syndrome in temporal epilepsy. MRI and neuropsychological methods were used to study brain structures. Results and сonclusion. Neurocognitive impairment was more severe in patients with depressive syndrome in the structure of temporal epilepsy. The differences between the patients with endogenous and organic (temporal epilepsy) affective disturbances were determined by the more marked memory and spatial-constructive impairments in patients with organic disorders. Deficit of executive functions, planning functions and cognitive organization were more typical for the patients with endogenous affective disorders. The MRI study revealed the decrease in the left hippocampus due to sclerotic processes in patients with temporal epilepsy and the increase in the right amygdale in patients with endogenous depressive disorders. The results demonstrate the significant similarity between characteristics of the cognitive profile in patients with endo- and exogenous depressions.

6.
Rev. colomb. quím. (Bogotá) ; 44(1): 5-10, ene.-jun. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-774956

ABSTRACT

Los telómeros son estructuras complejas de ADN y proteína localizadas en el extremo de los cromosomas eucariotes. Su principal función es proteger el extremo cromosomal de ser reconocido y procesado como ADNs fracturado, evitando así eventos de recombinación y fusión que conducen a inestabilidad cromosomal. El ADN telomérico consta de secuencias cortas, repetidas una tras otra, ricas en guanina; la cadena rica en guanina se extiende formando una región de cadena sencilla denominada extremo 3' protuberante. Las proteínas por su parte, se pueden clasificar en: dsBPs, o proteínas de unión a la cadena doble, GBPs aquellas que reconocen específicamente el extremo protuberante y, proteínas que las interconectan mediante interacciones proteína-proteína. El gen PF3D7_1006800 de Plasmodium falciparum codifica para una proteína putativa similar a una GBP de Criptosporidium parvum, con el fin de establecer si esta proteína de P. falciparum presenta la capacidad de unión al ADN telomérico del parásito, se produjo una proteína recombinante a partir de la región codificante del gen, se purificó y se utilizó en ensayos de unión a ADN, y en la generación de anticuerpos policlonales específicos contra PfGBP. Nuestros resultados indican que la proteína de P. falciparum es una proteína nuclear con capacidad de unión al ADN telomérico in vitro, por lo que podría ser parte del complejo proteico encargado de proteger y/o mantener el telómero in vivo.


Telomeres are specialized structures at the end of chromosomes that consist of repetitive DNA sequences and associated proteins. The primary role of telomeres is to protect the end of linear chromosomes from recombination, fusion, and recognition as broken DNA ends. This protective function can be achieved through association with specific telomere binding proteins. Telomeric DNA consists of G-rich double-stranded arrays followed by a single-stranded G-rich overhang. The telomeric proteins can be classified in dsBPs, which bind double-stranded DNA, GBPs those that bind specifically to G-rich overhang, and proteins that interact with telomeric factors. Plasmodium falciparum gene PF3D7_1006800 codifies for a protein highly similar to Cryptosporidium parvum GBP. In order to investigate whether the P. falciparum protein binds telomeric DNA, a recombinant protein was produced, purified and DNA binding assays were performed. Polyclonal antibodies against rPfGBP were produced and tested in western blot. Our results indicate that PfGBP is a nuclear protein that binds telomeric DNA in vitro, which could be part of the protein complex responsible for protecting and/or maintaining the telomere in vivo.


Os telómeros são estruturas complexas de DNA e proteína localizadas no extremo dos cromossomas dos eucariotas. Sua principal função é proteger o extremo dos cromossomas para que não sejam reconhecidos e processados como DNAs fraturados. O anterior evita eventos de recombinação e fusão que conduzem à instabilidade nos cromossomas. O DNA telomérico tem sequencias curtas e repetidas, ricas em guanina. A cadeia rica em guanina estende-se para formar uma região de cadeia simples chamada extremo 3' protuberante. As proteínas podem-se classificar em: dsBPs ou proteínas de união à cadeia dupla, GBPs que são as que reconhecem especificamente o extremo protuberante e, as proteínas que interligam mediante interações proteína-proteína. O gene PF3D7_1006800 de Plasmodium falciparum codifica para uma proteína similar a uma GBP de Criptosporidium parvum. Com o objetivo de estabelecer se a proteína de P. falciparum presenta a capacidade de união ao DNA telomérico, foi produzida uma proteína recombinante partindo da região codificante do gene, purificou-se e utilizou-se nos ensaios de união ao DNA e na geração de anticorpos policlonais específicos contra PfGBP. Os nossos resultados indicam que a proteína de P. falciparum é uma proteína nuclear com capacidade de união ao DNA telomérico in vitro, pelo que poderia fazer parte do complexo proteico encarregado de proteger e/ou manter o telómero in vivo.

7.
Surg Endosc ; 29(6): 1462-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25159656

ABSTRACT

BACKGROUND: Laparoscopic Heller myotomy with partial fundoplication is the gold standard treatment for achalasia. Laparoscopic limited Heller myotomy (LLHM) with no anti-reflux procedure is another possible option. METHODS: A review of prospectively collected data was performed on patients who underwent LLHM from January 1998 to December 2012. Evaluation included gastroscopy, esophageal manometry, 24-h pH-metry, and the Short Form(36) Health Survey(SF-36) questionnaire at baseline and 6 months, as well as the global symptom score at baseline, 6 months, and 5 years post-surgery. Comparison between outcomes was performed with a paired t student's test. RESULTS: 126 patients underwent LLHM. Of these, 60 patients had complete pre and post-operative motility studies. 57 % were female, patient mean age was 45.7 years, with a mean follow-up of 10.53 months. Mean operative time was 56.1 min, and the average length of stay was 1.7 days. At 6 months, a significant decrease in the lower esophageal sphincter resting pressure (29.1 vs. 7.1 mmHg; p < 0.001) and nadir (16.4 vs. 4.3 mmHg; p < 0.001) was observed. Normal esophageal acid exposure (total pH < 4 %) was observed in 68.3 % patients. Nevertheless, of the remaining 31.7 % with abnormal pH-metry, only 21.6 % were clinically symptomatic and all were properly controlled with medical treatment without requiring anti-reflux surgery. Significant improvement in all pre-operative symptoms was observed at 6 months and maintained over 5 years. Dysphagia score was reduced from 9.8 pre-operatively to 2.6 at 5 years (p < 0.001), heartburn score from 3.82 to 2 (p < 0.01), and regurgitation score from 7.5 to 0.8 (p < 0.001). Only one patient (0.8 %) presented with recurrent dysphagia requiring reoperation. CONCLUSION: LLHM without anti-reflux procedure is an effective long-term treatment for achalasia and does not cause symptomatic GERD in three quarters of patients. The remaining patients are well controlled on anti-reflux medications. It is believed that similar clinical results would be obtained during a clinical investigation of the POEM procedure.


Subject(s)
Esophageal Achalasia/surgery , Esophageal Sphincter, Lower/surgery , Gastroesophageal Reflux/etiology , Laparoscopy/methods , Postoperative Complications , Adolescent , Adult , Aged , Female , Follow-Up Studies , Fundoplication/methods , Gastroesophageal Reflux/prevention & control , Humans , Male , Middle Aged , Operative Time , Postoperative Complications/prevention & control , Reoperation , Retrospective Studies , Treatment Outcome , Young Adult
8.
Endocrinology ; 153(8): 4039-48, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22719054

ABSTRACT

The type 2 iodothyronine selenodeiodinase (D2) is a critical determinant of local thyroid signaling, converting T(4) to the active form T(3) at the cytoplasmic face of the endoplasmic reticulum, thus supplying the nucleus with T(3) without immediately affecting circulating thyroid hormone levels. Although inhibitors of the cholesterol synthesis/isoprenylation pathway, such as hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins) have been to shown to down-regulate selenoproteins via interruption of normal selenocysteine incorporation, little is known about the effect of statins on D2. Here, we report that statins and prenyl transferase inhibitors actually increase D2 activity in cells with endogenous D2 expression. Although we confirmed that lovastatin (LVS) decreases the activity of transiently expressed D2 in HEK-293 cells, the prenyl transferase inhibitors increase activity in this system as well. LVS treatment increases endogenous Dio2 mRNA in MSTO-211H cells but does not alter transiently expressed Dio2 mRNA in HEK-293 cells. The prenyl transferase inhibitors do not increase Dio2 mRNA in either system, indicating that a posttranscriptional mechanism must exist. Cotreatment with LVS or the prenyl transferase inhibitors with the proteasome inhibitor MG-132 did not lead to additive increases in D2 activity, indirectly implicating the ubiquitin-proteasomal system in the mechanism. Finally, C57BL/6J mice treated with LVS or farnesyl transferase inhibitor-277 for 24 h exhibited increased D2 activity in their brown adipose tissue. These data indicate that statins and downstream inhibitors of the isoprenylation pathway may increase thyroid signaling via stimulation of D2 activity.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Iodide Peroxidase/metabolism , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Cell Line , Cell Line, Tumor , Enzyme Activation/drug effects , HEK293 Cells , Humans , In Vitro Techniques , Iodide Peroxidase/genetics , Leupeptins/pharmacology , Lovastatin/pharmacology , Male , Mice , Mice, Inbred C57BL , Iodothyronine Deiodinase Type II
9.
Biochemistry (Mosc) ; 74(6): 633-42, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19645668

ABSTRACT

The damaging effect of UV radiation (lambda > 260 nm) on bovine alpha-crystallin in solution was studied by small-angle X-ray scattering, gel permeation chromatography, electrophoresis, absorption and fluorescence spectroscopy, and differential scanning calorimetry. The results obtained show that damage to even a large number of subunits within an alpha-crystallin oligomer does not cause significant rearrangement of its quaternary structure, aggregation of oligomers, or the loss of their solubility. Due to the high resistance of its quaternary structure, alpha-crystallin is able to prevent aggregation of destabilized proteins (especially of gamma- and beta-crystallins) and so to maintain lens transparency throughout the life of an animal (the chaperone-like function of alpha-crystallin).


Subject(s)
Protein Structure, Quaternary/radiation effects , Ultraviolet Rays/adverse effects , alpha-Crystallins/chemistry , Animals , Calorimetry, Differential Scanning , Cattle , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Lens Cortex, Crystalline/chemistry , Protein Denaturation , Scattering, Small Angle , Spectrometry, Fluorescence , Spectrophotometry , alpha-Crystallins/isolation & purification , alpha-Crystallins/radiation effects
10.
IEEE Trans Biomed Circuits Syst ; 1(1): 73-84, 2007 Mar.
Article in English | MEDLINE | ID: mdl-23851523

ABSTRACT

A very large format neural stimulator device, to be used in future retinal prosthesis experiments, has been designed, fabricated, and tested. The device was designed to be positioned against a human retina for short periods in an operating room environment. Demonstrating a very large format, parallel interface between a 2-D microelectronic stimulator array and neural tissue would be an important step in proving the feasibility of high resolution retinal prosthesis for the blind. The architecture of the test device combines several novel components, including microwire glass, a microelectronic multiplexer, and a microcable connector. The array format is 80 times 40 array pixels with approximately 20 microwire electrodes per pixel. The custom assembly techniques involve indium bump bonding, ribbon bonding, and encapsulation. The design, fabrication, and testing of the device has resolved several important issues regarding the feasibility of high-resolution retinal prosthesis, namely, that the combination of conventional CMOS electronics and microwire glass provides a viable approach for a high resolution retinal prosthesis device. Temperature change from power dissipation within the device and maximum electrical output current levels suggest that the device is acceptable for acute human tests.

11.
Probl Endokrinol (Mosk) ; 52(1): 6-10, 2006 Feb 15.
Article in Russian | MEDLINE | ID: mdl-31627673

ABSTRACT

A hundred and twenty-six outpatients (41 males and 75 females) with type 1 diabetes mellitus were examined to study the affective and personal determinants of their attitude towards the disease at the Saint Petersburg City Diabetes Center within the framework of cooperation of the V. M. Bekhterev Psychoneurological Research Institute and the Academician I. P. Pavlov Saint Petersburg State Medical University. The examinees' mean age was 31.8±10.1 years. The mean duration of the disease was 17.1±8.3 years. Most patients were found to have symptoms of late diabetic complications. The patients' attitude towards the disease and their affective and personal characteristics were examined, by using a test for the psychological diagnosis of the types of an attitude towards the disease, scales for the rapid psychological diagnosis of neurotization, and the questionnaire "Copying ways". Analysis of the results led to the following conclusions: the probability of hypemosognostic reactions in patients with type 1 diabetes mellitus is relatively independent of the objectively assessed severity of the disease; the affective and personality characteristics associated with hypemeurotization considerably increase the risk of the hypemosognostic type of the internal picture of the disease, which is largely mediated by a tendency for avoidance behavior and by the lack of stress-coping behavioral skills, mainly problem solution-planning and self-regulation skills. Psychological correction aimed at enhancing the emotional stability of a personality and developing stress-coping skills seems to improve the adaptation of patients with type 1 diabetes mellitus to their disease.

12.
Int J Obes Relat Metab Disord ; 28(1): 49-56, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14557830

ABSTRACT

BACKGROUND: Obesity in women has been associated with a variety of factors, including genetic predisposition, social class, early age at menarche, exercise, alcohol consumption and diet. Obesity is a risk factor for the occurrence and the recurrence of breast cancer in postmenopausal women, perhaps because of increased exposure to estrogen, insulin and insulin-like growth factors (IGFs). The progesterone receptor (PR) and the steroid hormone receptor coactivator pCIP/ACTR/AIB1/TRAM1/RAC3 (AIB1) are hypothesized to mediate signaling crosstalk between these hormonal pathways. Polymorphisms in both genes have been described and their association with breast cancer risk reported. If genetic factors contribute to obesity, and the PR and AIB1 genes influence estrogenic, insulin and IGF pathways, then genetic patterns resulting from PR and AIB1 polymorphisms may be associated with obesity in postmenopausal women. OBJECTIVE: We compared the PR and AIB1 genotypes of postmenopausal women with breast cancer with demographic, disease-related, reproductive, lifestyle and dietary variables in terms of the strength of their relationship with obesity (BMI> or =30 kg/m2). SUBJECTS: A total of 301 postmenopausal women previously diagnosed with Stage I, II or IIIA breast cancer, who are enrolled in the Women's Healthy Eating and Living (WHEL) study (age: 34.5-70.8 y, BMI: 17.8-54.6 kg/m2). MEASUREMENTS: The PR polymorphism PROGINS was identified by PCR. The length of the AIB1 polyglutamine repeat was determined by PCR and nondenaturing gel electrophoresis or DNA sequencing. BMI was obtained at the baseline clinic visit upon entry into the WHEL study. Information about date of diagnosis, stage of disease, tumor hormone receptor status and adjuvant treatment received were obtained from medical records. Reproductive, menstrual history, demographic, family history of cancer, smoking history and exercise frequency and intensity information were obtained from questionnaires. Dietary and alcohol intake data came from four 24-h telephone recalls of food intake obtained at the study entry. RESULTS: The combined inheritance of PROGINS A1/A1 and AIB1 28/29, 28/30, 28/31, 29/29 or 29/30 (AIB1 LG) genotypes (adjusted odds ratio (OR)=2.22 (95% confidence interval 1.25-3.93)) and early age at menarche (<12 y) (adjusted OR=2.34 (1.12-4.86)) were each associated with the risk for obesity. Current use of tamoxifen (adjusted OR=0.49 (0.28-0.87)) and an alcohol intake > or =10 g/day (adjusted OR=0.28 (0.11-0.77)) were inversely associated with BMI > or =30 kg/m2. CONCLUSION: Early age at menarche and a PROGINS A1/A1+AIB1 LG genetic pattern had comparable levels of association with obesity in this cross-sectional sample of postmenopausal women with breast cancer. Since this was a cross-sectional rather than a case-control design, the association between PROGINS and AIB1 genotype and obesity found in this sample should be considered preliminary, and must be re-evaluated with a new and larger sample.


Subject(s)
Breast Neoplasms/genetics , Obesity/genetics , Postmenopause/genetics , Receptors, Progesterone/genetics , Transcription Factors/genetics , Adult , Aged , Body Mass Index , Cross-Sectional Studies , Diet , Energy Intake , Female , Genotype , Humans , Life Style , Menarche/physiology , Middle Aged , Nuclear Receptor Coactivator 3 , Polymorphism, Genetic/genetics , Regression Analysis , Risk Factors
14.
Nature ; 424(6945): 165-8, 2003 Jul 10.
Article in English | MEDLINE | ID: mdl-12853949

ABSTRACT

Stellar occultations--the passing of a relatively nearby body in front of a background star--can be used to probe the atmosphere of the closer body with a spatial resolution of a few kilometres (ref. 1). Such observations can yield the scale height, temperature profile, and other information about the structure of the occulting atmosphere. Occultation data acquired for Pluto's atmosphere in 1988 revealed a nearly isothermal atmosphere above a radius of approximately 1,215 km. Below this level, the data could be interpreted as indicating either an extinction layer or the onset of a large thermal gradient, calling into question the fundamental structure of this atmosphere. Another question is to what extent Pluto's atmosphere might be collapsing as it recedes from the Sun (passing perihelion in 1989 in its 248-year orbital period), owing to the extreme sensitivity of the equilibrium surface pressure to the surface temperature. Here we report observations at a variety of visible and infrared wavelengths of an occultation of a star by Pluto in August 2002. These data reveal evidence for extinction in Pluto's atmosphere and show that it has indeed changed, having expanded rather than collapsed, since 1988.

16.
Psychon Bull Rev ; 8(2): 244-61, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11495112

ABSTRACT

Traditional color vision theory posits that three types of retinal photopigments transduce light into a trivariate neural color code, thereby explaining color-matching behaviors. This principle of trichromacy is in need of reexamination in view of molecular genetics results suggesting that a substantial percentage of women possess more than three classes of retinal photopigments. At issue is the question of whether four-photopigment retinas necessarily yield trichromatic color perception. In the present paper, we review results and theory underlying the accepted photoreceptor-based model of trichromacy. A review of the psychological literature shows that gender-linked differences in color perception warrant further investigation of retinal photopigment classes and color perception relations. We use genetic analyses to examine an important position in the gene sequence, and we empirically assess and compare the color perception of individuals possessing more than three retinal photopigment genes with those possessing fewer retinal photopigment genes. Women with four-photopigment genotypes are found to perceive significantly more chromatic appearances in comparison with either male or female trichromat controls. We provide a rationale for this previously undetected finding and discuss implications for theories of color perception and gender differences in color behavior.


Subject(s)
Color Perception/genetics , Rod Opsins/genetics , Adult , Female , Genotype , Humans , Male , Retina/physiology , Sex Factors
18.
Stat Med ; 20(11): 1681-91, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11391695

ABSTRACT

We describe a methodology for model comparison in a Bayesian framework as applied to survival with a surviving fraction. This is illustrated using a case study of a randomized and controlled clinical trial investigating time until recurrence of depression. Posterior distributions are simulated using Metropolis-within-Gibbs Markov chain methods. Models reflecting the effects of covariates on the log odds of being in the surviving fraction, the log of the hazard rate, as well as both and neither are compared. Bayes factors for comparing the models are obtained by using the bridge sampling method of calculating normalizing constants.


Subject(s)
Bayes Theorem , Models, Biological , Survival Analysis , Algorithms , Antidepressive Agents, Tricyclic/therapeutic use , Computer Simulation , Depression/drug therapy , Depression/prevention & control , Disease-Free Survival , Humans , Imipramine/therapeutic use , Markov Chains , Multicenter Studies as Topic/methods , Randomized Controlled Trials as Topic/methods
19.
Neurosci Lett ; 303(1): 45-8, 2001 Apr 27.
Article in English | MEDLINE | ID: mdl-11297820

ABSTRACT

Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is still unclear. Evidence has accumulated indicating that it reflects dopamine deficiency associated with defective arborization of dopaminergic dendrites. We monitored the differentiation in vitro of dopaminergic neurons, cultured from HPRT-deficient knockout mice. The HPRT-deficient dopaminergic neurons exhibited a decelerated rate of outgrowth of dendrites in comparison to that of control neurons resulting, after 8 days in culture, in 32% smaller average total length of dendrites per neuron (P<0.025). The results suggest that the abnormal dendrite outgrowth in LNS reflects a defective developmental process.


Subject(s)
Brain/physiology , Dendrites/physiology , Dopamine/deficiency , Hypoxanthine Phosphoribosyltransferase/deficiency , Animals , Cells, Cultured , Lesch-Nyhan Syndrome/physiopathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons/physiology
20.
Breast Cancer Res Treat ; 70(1): 27-37, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11767002

ABSTRACT

Recent studies from our laboratory have revealed that basic fibroblast growth factor (bFGF) selectively inhibits the proliferation of human MCF-7 breast cancer cells. It has also been shown to enhance cis-platinum-induced apoptosis, decrease levels of the anti-apoptotic gene product bcl-2, and increase levels of the cyclin-dependent protein kinase inhibitor p21/WAF1/Cip1. Transforming growth factor beta-1 (TGFbeta1), a cell growth regulator has been found to have an inhibitory effect on breast cancer cells. The aim of the present study was to evaluate the possible role of TGFbeta1 in the antiproliferative effects of bFGF in MCF-7 breast cancer cells. We found that exogenous, as well as endogenous (overexpressed) bFGF increased TGFbeta1 mRNA expression in the cells and enhanced the secretion of TGFbeta1 into culture medium. However, exogenous addition of TGFbeta1 neither led to a decrease in bcl-2 nor induced an increase in the levels of p21/WAF1/Cip1 and neutralizing antibodies to TGFbeta1, did not reverse bFGF-induced G1 arrest northe increase in p21/WAF1/Cip1 level. In contrast, antisense oligonucleotides to TGFbeta1 abrogated the antiproliferative effects and inhibited the induction of p21/WAF1/Cip1 by bFGF in MCF-7 cells. These data suggest that the anti-proliferative effects of bFGF in human MCF-7 breast cancer cells are mediated by endogenous TGFbeta1, while exogenous TGFbeta1 does not mimic all the effects of bFGF on these breast cancer cells. These findings provide an important basis for further investigations into the autocrine and paracrine processes that control the growth of breast cancer cells.


Subject(s)
Angiogenesis Inhibitors/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cyclins/metabolism , Fibroblast Growth Factor 2/metabolism , Growth Inhibitors/metabolism , Transforming Growth Factor beta/metabolism , Angiogenesis Inhibitors/pharmacology , Blotting, Northern , Blotting, Western , Breast Neoplasms/blood supply , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/genetics , Female , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/pharmacology , Gene Expression Profiling , Growth Inhibitors/genetics , Humans , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/prevention & control , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/pharmacology , Transforming Growth Factor beta1 , Tumor Cells, Cultured
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