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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin has a powerful effect on fertility and the initiation of puberty in addition to its effect on obesity. It has been suggested that that in times of fasting, infertility induced by low leptin levels protect the female from the energy demands of pregnancy. Despite this there have been no studies of the potential role of LEP gene variants on the age of onset of menarche. We genotyped 183 non-Hispanic Caucasian adult females at the LEP D7S1875 dinucleotide repeat polymorphism. The alleles were placed into three genotypes, <208/<208 bp, heterozygotes, and > or =208/> or =208 bp. A hierarchical ANOVA was performed with age of menarche as the dependent variable and LEP(1875) genotypes and maternal age (age of the mothers at birth of the subject) as independent variables. There was a significant (P </= 0.006) interaction of LEP(1875) x maternal age but neither independent variable was significant by itself. This was due to an "association crossover effect" in which the LEP(1875) by age of menarche effects were in opposite directions for those with a maternal age of <30 years compared to those with a maternal age of > or =30 years. If maternal age effects prove to be generalized, failure to take them into consideration could provide a source of hidden stratification that could significantly alter the replication of association studies.
Mol Genet Metab 2001 Jul
PMID:The LEP gene and age of menarche: maternal age as a potential cause of hidden stratification in association studies. 1146 Nov 87

Chronic bilateral common carotid artery occlusion (BCCAO) induces moderate ischemia (oligemia) in the rat forebrain in the absence of overt neuronal damage. In situ hybridization for brain-derived neurotrophic factor (BDNF) mRNA was used to search for a molecular response to moderate ischemia. BDNF mRNA was significantly increased in the hippocampal granule cells at 6 h of occlusion (ANOVA, Tukey test P<0.05). At 1, 7 and 14 days BDNF mRNA levels returned to control levels. The frequency of BDNF gene expression at 6 h was 83%, which was significantly higher than the 7% incidence of histological injury in the hippocampus (Fisher's exact test, P<0.002). Cerebral blood flow was reduced to 75% of control levels in the hippocampus after 1 week of BCCAO when measured with the autoradiographic method. Measurements of tissue flow with a microprobe for laser Doppler flow excluded decreases into the ischemic range during the period when elevated gene expression was observed. Prolonged moderate ischemia (oligemia) is a sufficient stimulus for BDNF gene expression in the hippocampus. These molecular studies provide direct evidence for an involvement of the hippocampus in the BCCAO model.
Brain Res Mol Brain Res 2001 Aug 15
PMID:Transient changes of brain-derived neurotrophic factor (BDNF) mRNA expression in hippocampus during moderate ischemia induced by chronic bilateral common carotid artery occlusions in the rat. 1148 52

GLABROUS1 (GL1) belongs to the large family of MYB transcription factors and is known to play a central role in trichome initiation. We studied trichome distribution and the molecular variation of GL1 in 28 A. thaliana accessions. Trichome density on rosette leaves was highly variable among those accessions. On the molecular level, we detected substantial sequence variation in a 3-kb fragment which included the complete coding region of the GL1 locus (pi = 0.01). Phylogenetic analysis of GL1 indicates the presence of two diverged clades among 28 accessions. Using ANOVA, we show that the phenotypic variation in trichome density cannot be explained by the sequence divergence between the two phylogenetic lineages. Sequence analysis of wild-type Arabidopsis thaliana and Arabidopsis lyrata accessions indicates that all amino acid substitutions are located outside of the conserved helix-turn-helix DNA-binding domains R2 and R3. Using plants of A. thaliana and A. lyrata with either naturally occurring or ethyl methane sulfonate--induced glabrous phenotypes, we demonstrate that the last 14 C-terminal amino acids of the GL1 gene have no major impact on the initiation of trichomes.
Mol Biol Evol 2001 Sep
PMID:Trichome distribution in Arabidopsis thaliana and its close relative Arabidopsis lyrata: molecular analysis of the candidate gene GLABROUS1. 1150 55

The age-associated changes in dopamine subtype receptors were examined in Aplysia californica. The density of the subtype receptors D1, D2, D3 and D4 was examined in the ganglia from 4.5-, 6-, 8-, 9- and 12-month animals. Receptor analysis was performed by examining the binding of radiolabeled ligands to the individual subtypes. [3H]SCH23390 and [3H]Clozapine were used to analyze D1 and D4 specific binding. [3H]Quinpirole was used for determining D2 and D3 specific binding. Specific binding was found to be present for all four receptor subtypes. All receptor subtypes showed an increase in density from 4.5 to 6 months. From 6 to 8 months D2 and D3 decreased, while D1 and D4 increased. D4 showed the strongest increase. All four subtypes examined showed decreases from 8 to 12 months. ANOVA results indicated age was a significant factor in the subtype receptor density for all receptor types.
Comp Biochem Physiol B Biochem Mol Biol 2001 Dec
PMID:Dopamine receptor subtype density as a function of age in Aplysia californica. 1169 23

There is evidence that oxidative stress plays a role in the development of chronic lung disease (CLD), with immature lungs being particularly sensitive to the injurious effect of oxygen and mechanical ventilation. We analyzed total ascorbate, urate, and protein carbonyls in 102 bronchoalveolar lavage fluid samples from 38 babies (33 preterm, 24-36 wk gestation; 5 term, 37-39 wk gestation). Preterm babies had significantly decreasing concentrations of ascorbate, urate, and protein carbonyls during the first 9 days of life (days 1-3, 4-6, and 7-9, Kruskal-Wallis ANOVA: P = 0.016, P < 0.0001, and P = 0.010, respectively). Preterm babies had significantly higher protein carbonyl concentrations at days 1-3 and 4-6 (P = 0.005 and P = 0.044) compared with term babies. Very preterm babies (24-28 wk gestation) had increased concentrations of protein carbonyls at days 4-6 (P = 0.056) and significantly decreased ascorbate concentrations at days 4-6 (P = 0.004) compared with preterm babies (29-36 wk gestation). Urate concentrations were significantly elevated at days 1-3 (P = 0.023) in preterm babies who subsequently developed CLD. This study has shown the presence of oxidative stress in the lungs of preterm babies during ventilation, especially in those who subsequently developed CLD.
Am J Physiol Lung Cell Mol Physiol 2001 Dec
PMID:Oxidative stress in lavage fluid of preterm infants at risk of chronic lung disease. 1170 34

Cardiac autonomic dysfunction is common in heart disease with or without congestive heart failure, and can cause sudden cardiac death. However, cardiac autonomic abnormalities in non-ischemic (hypertensive) heart failure, which is prevalent in Black Africans is poorly documented. We conducted a cross-sectional study of 32 patients with congestive heart failure, mostly secondary to hypertension (aged 52 +/- 15 years, with ejection fraction of 0.38 +/- 11) and 30 age- and sex-matched healthy volunteers (aged 51 +/- 11 years, 14 males/16 females). Cardiac autonomic function was assessed by the Valsalva's maneuver, respiratory sinus arrhythmia (for cardiac vagal tone) and the pressor and chronotropic changes following forearm isometric handgrip exercise and the assumption of upright posture (tests of sympathetic function). The exercise tolerance of the cardiac patients was assessed by the distance covered during 6 min of walking. The Valsalva ratio was significantly lower in chronic heart failure, 1.10 +/- 0.08 compared to the healthy controls 1.47 +/- 0.20 (p<0.001). Specifically, the phase IV bradycardia in heart failure, was significantly attenuated to 650 +/- 121 msec compared to the value of 935 +/- 101 msec in healthy controls (p<0.001). The phase 11 Valsalva tachycardia did not differ between the patients and controls. The respiratory sinus arrhythmia was also significantly reduced in chronic heart failure (p<0.05) compared to controls. Treatment of the heart failure patients with enalapril-digoxin and diuretics by 4 weeks, resulted in a reversal of the autonomic abnormalities. The phase IV bradycardia increased significantly to 798 +/- 164 msec (p<0.01) and the Valsalva ratio to 1.35 +/- 0.25 (p<0.01) and the respiratory sinus arrhythmia increased toward normal. There was close positive correlation between the Valsalva's ratio and the 6 min self paced distance covered (r = 0.44, p = 0.03 ANOVA), and a weak inverse correlation to cardiac size and cardiothoracic ratio (r = -0.31, p = 0.09). This study demonstrates cardiac autonomic dysfunction (especially reduced vagal tone) in Black Nigerians with mainly non-ischemic congestive heart failure. The parasympathetic dysfunction significantly correlates with severity of heart failure. Current treatment reverses autonomic dysfunction to values seen in healthy age matched controls, mainly through augmentation of cardiac parasympathetic activity.
Cell Mol Biol (Noisy-le-grand) 2001 Sep
PMID:Cardiac autonomic function in Blacks with congestive heart failure: vagomimetic action, alteration in sympathovagal balance, and the effect of ACE inhibition on central and peripheral vagal tone. 1178 58

Dynamic imaging of the inflow of technetium-99m hexamethylpropylene amine oxime (HMPAO) to the brain has been proved to allow estimation of the hemispherical cerebral blood flow (CBF) using the Patlak plot. In this study, we compared the hemispherical CBF (in ml/min/100 g) of different patient groups. A total of 25 patients (comprising 13 with migraine and 12 scheduled for endarterectomy owing to angiographically confirmed severe stenosis of the internal carotid artery on at least one side) underwent baseline and acetazolamide 99mTc-HMPAO brain perfusion studies. In addition, acetazolamide 99mTc-HMPAO studies were performed in 12 healthy subjects (no baseline study was performed for ethical reasons.) Dynamic studies were acquired by means of a dual-detector gamma camera with a large field of view (HELIX, Elscint). Special difference images were created to make definition of the aortic arch and hemispherical brain regions easier and more reproducible. A semi-automatic method was developed to determine the transit time from the aorta to the brain, making the generation of the Patlak plot even more robust. The baseline CBF values did not significantly depend on the disease (P>0.1), whereas the CBF values obtained after acetazolamide provocation did do so (ANOVA, P<0.001). Patients suffering from migraine showed a significant increase in global CBF values after acetazolamide provocation (paired t test, P<0.05), but we could not find any effect of the provocation in patients awaiting carotid endarterectomy, indicating a lack of cerebrovascular reserve capacity. Comparison of the results of the acetazolamide study in patients and the control group revealed the CBF values to be significantly lower in patients with carotid stenosis (two-sample t-test, P<0.001), but not in those with migraine (P>0.1). In summary, using quantitative analysis of 99mTc-HMPAO brain studies we could objectively compare the CBF of patients suffering from different diseases. Especially the CBF values obtained after acetazolamide provocation permitted effective differentiation of disease states. The quantitative results may be of assistance in therapy planning, e.g. in selection of the correct operative technique.
Eur J Nucl Med Mol Imaging 2002 Feb
PMID:Quantitative assessment of blood flow reserve using 99mTc-HMPAO in carotid stenosis. 1192 83

Post-mortem specimens from the Stanley Foundation Neuropathology Consortium, which contains matched samples from patients with schizophrenia, bipolar disorder, non-psychotic depression and normal controls (n = 15 per group), have been distributed to many research groups around the world. This paper provides a summary of abnormal markers found in prefrontal cortical areas from this collection between 1997 and 2001. With parametric analyses of variance of 102 separate data sets, 14 markers were abnormal in at least one disease. The markers pertained to a variety of neural systems and processes including neuronal plasticity, neurotransmission, signal transduction, inhibitory interneuron function and glial cells. The data sets were also examined using the non-parametric Classification and Regression Tree (CRT) technique for the four diagnostic groups and in pair-wise combinations. In contrast to the results obtained with analyses of variance, the CRT method identified a smaller set of nine markers that contributed maximally to the diagnostic classifications. Three of the nine markers observed with CRT overlapped with the ANOVA results. Six of the nine markers observed with the CRT technique pertained to aspects of glutamatergic, GABA-ergic, and dopaminergic neurotransmission.
Mol Psychiatry 2002
PMID:Molecular abnormalities in the major psychiatric illnesses: Classification and Regression Tree (CRT) analysis of post-mortem prefrontal markers. 1198 83

Recent imaging and postmortem studies suggest that impaired connectivity is involved in the pathophysiology of schizophrenia and major affective disorders. We investigated the presynaptic proteins complexin (Cx) I and Cx II in postmortem prefrontal cortex in schizophrenia (n = 13; six suicide, seven nonsuicide), major depression (n= 11, all suicide) and controls (n = 11) with an enzyme-linked immunoadsorbent assay (ELISA). Overall analysis indicated a significant difference between groups (F = 3.93, P = 0.007). Cx I (enriched in inhibitory terminals) was decreased 33% in schizophrenia (26% in schizophrenia/nonsuicide, 42% in schizophrenia/suicide) and 27% in major depression. Cx II (enriched in excitatory terminals) was not significantly different. Analysis of the ratio of Cx II/Cx I was carried out as an indication of the balance of excitatory to inhibitory terminals. A significant difference between groups (ANOVA, F = 6.42, P = 0.005) was observed. The mean value of Cx II/Cx I was significantly increased by 34% in schizophrenia (26% in schizophrenia/nonsuicide and 43% in schizophrenia/suicide) and by 32% in depression compared with control (Student-Newman-Keuls test, P = 0.05). Immunoreactivities of the two complexins were highly correlated in all groups. However, compared with controls and depression, samples from cases with schizophrenia appeared to have relatively less Cx I for similar amounts of Cx II. Immunocytochemical studies of rat frontal cortex after 3 weeks treatment with chlorpromazine, trifluoperazine or haloperidol revealed no differences in complexins, synaptophysin, SNAP-25, syntaxin or VAMP in comparison with animals treated with vehicle. Alterations of complexins may contribute to the molecular substrate for abnormalities of neural connectivity in severe mental disorders.
Mol Psychiatry 2002
PMID:Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness. 1208 66

Sensorineural hearing loss is found in many inherited forms of muscular dystrophy. We investigated the dy mouse model, which has congenital muscular dystrophy due to a defect in laminin alpha 2, for evidence of cochlear dysfunction. Auditory brainstem response (ABR) audiometry to pure tones was used to evaluate 3-month-old homozygous dy/dy and age-matched C57 control mice. The average ABR thresholds to tone-burst stimuli for four frequencies (4, 8, 16, and 32 kHz) were determined and statistically compared by ANOVA. The dy/dy mice demonstrated elevated auditory thresholds ranging from 25 to 27 dB at each frequency tested (p<0.0001). Anatomic evaluations of the ears revealed pathology ranging from extensive connective tissue infiltration within the inner ear to possible minor defects in the cells of the organ of Corti. These anatomic and physiologic observations suggest that the extracellular matrix protein laminin plays a crucial role in normal cochlear function. Furthermore, the dy congenital muscular dystrophy mouse offers a novel model for evaluation of sensorineural hearing loss associated with muscular dystrophy.
Mol Genet Metab 2002 Jul
PMID:Hearing loss in the laminin-deficient dy mouse model of congenital muscular dystrophy. 1212 36


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