Effects of estradiol on very low density lipoprotein receptor mRNA levels in rabbit heart

AbstractThe VLDL receptor, a newly identified lipoprotein receptor, has a domain structure homologous with the LDL receptor but has one additional cysteine rich repeat in the ligand binding domain. To study the regulation of the VLDL receptor in vivo, we administered 17 α-ethinyl estradiol to rabbits and examined its effects on VLDL receptor mRNA levels in the heart, one of the organs with highly expressed VLDL receptors, by RNA blotting. The ventricular level of VLDL receptor mRNA increased dramatically after estradiol administration. We could not detect VLDL receptor mRNA in the liver even after estradiol administration. We have confirmed the enhanced expression of liver LDL receptor mRNA by estradiol, however, only weak expression of the LDL receptor was detected in the ventricle of the rabbit heart. These results suggest that estradiol exerts its effect on the VLDL receptor gene expression in the heart

The WD40-repeat protein Pwp1p associates in vivo with 25S ribosomal chromatin in a histone H4 tail-dependent manner

The tails of core histones (H2A, H2B, H3 and H4) are critical for the regulation of chromatin dynamics. Each core histone tail is specifically recognized by various tail binding proteins. Here we screened for budding yeast histone H4-tail binding proteins in a protein differential display approach by two-dimensional gel electrophoresis (2DGE). To obtain highly enriched chromatin proteins, we used a Mg(2+)-dependent chromatin oligomerization technique. The Mg(2+)-dependent oligomerized chromatin from H4-tail deleted cells was compared with that from wild-type cells. We used mass spectrometry to identify 22 candidate proteins whose amounts were reduced in the oligomerized chromatin from the H4-tail deleted cells. A Saccharomyces Genome Database search revealed 10 protein complexes, each of which contained more than two candidate proteins. Interestingly, 7 out of the 10 complexes have the potential to associate with the H4-tail. We obtained in vivo evidence, by a chromatin immunoprecipitation assay, that one of the candidate proteins, Pwp1p, associates with the 25S ribosomal DNA (rDNA) chromatin in an H4-tail-dependent manner. We propose that the complex containing Pwp1p regulates the transcription of rDNA. Our results demonstrate that the protein differential display approach by 2DGE, using a histone-tail mutant, is a powerful method to identify histone-tail binding proteins

Post-Cataract Surgery Visual Disturbance in a Retinitis Pigmentosa Patient with Asteroid Hyalosis

A patient with retinitis pigmentosa showed visual disturbances following successful cataract surgery. He had a dense asteroid hyalosis in the eye before cataract surgery. After the surgery he noticed that his vision became worse. The visual disturbance was explained as being caused by the progression of retinal degeneration. Although the electroretinogram was non-recordable, the degeneration of macular area appeared relatively small. We considered that dense asteroid hyalosis was responsible for his visual disturbances, and pars plana vitrectomy (PPV) was performed to remove the asteroid hyalosis. After the PPV, rapid improvement of his visual acuity was observed. Cataract surgery may affect the status of asteroid hyalosis and cause rapid visual loss. PPV should be considered for retinitis pigmentosa patients with dense asteroid hyalosis, especially when a large decrease in visual acuity is noted shortly after cataract surgery

Pathophysiology of massive infantile spasms: perspective on the putative role of the brain adrenal axis.

Massive infantile spasms are an age-specific seizure syndrome of infancy. Uniquely, the spasms respond to hormonal manipulation using adrenocorticotropic hormone (ACTH) or glucocorticoids. A hypothesis explaining the efficacy of hormonal therapy, age-specificity, multiple causative factors, and spontaneous resolution of infantile spasms is presented. Corticotropin-releasing hormone (CRH), an excitant neuropeptide suppressed by ACTH/steroids, is implicated. Evidence for the age-specific convulsant properties of CRH is presented, and a putative scenario in which a stress-induced enhancement of endogenous CRH-mediated seizures is discussed. Clinical testing of the CRH-excess theory and its therapeutic implications are suggested

Synaptic Depression Via Mglur1 Positive Allosteric Modulation Suppresses Cue-Induced Cocaine Craving

Cue-induced cocaine craving is a major cause of relapse in abstinent addicts. In rats, cue-induced craving progressively intensifies (incubates) during withdrawal from extended-access cocaine self-administration. After ~1 month of withdrawal, incubated craving is mediated by Ca(2+)-permeable AMPA receptors (CP-AMPARs) that accumulate in the nucleus accumbens (NAc). We found that decreased mGluR1 surface expression in the NAc preceded and enabled CP-AMPAR accumulation. Thus, restoring mGluR1 transmission by administering repeated injections of an mGluR1 positive allosteric modulator (PAM) prevented CP-AMPAR accumulation and incubation, whereas blocking mGluR1 transmission at even earlier withdrawal times accelerated CP-AMPAR accumulation. In studies conducted after prolonged withdrawal, when CP-AMPAR levels and cue-induced craving are high, we found that systemic administration of an mGluR1 PAM attenuated the expression of incubated craving by reducing CP-AMPAR transmission in the NAc to control levels. These results suggest a strategy in which recovering addicts could use a systemically active compound to protect against cue-induced relapse

特発性正常圧水頭症におけるアルツハイマー病脳脊髄液バイオマーカーの動的モニタリング

京都大学0048新制・課程博士博士(医学)甲第22636号医博第4619号新制||医||1044(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 高橋 淳, 教授 古川 壽亮, 教授 村井 俊哉学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Anterior Choroidal Artery Infarction Evaluated with ¹²³I-Imp Single-Photon Emission Computed Tomography and 7 Tesla Magnetic Resonance Imaging

Anterior choroidal artery (AchA) infarction remains a challenging diagnosis although it was first described almost 100 years prior. N-isopropyl-p-[¹²³I]-iodoamphetamine single-photon emission computed tomography (¹²³I-IMP SPECT) and 7 Tesla magnetic resonance angiography (7T-MRA) are not routinely performed in cases of AchA infarction. Therefore, the application of ¹²³I-IMP SPECT and 7T-MRA for AchA infarction has not been reported previously. A 67-year-old man presented with disturbed consciousness, gaze preference to the left, aphasia, right homonymous hemianopia, and right hemiparesis. Brain magnetic resonance imaging revealed infarction of the left posterior limb of the internal capsule. Left middle cerebral artery was clearly seen on MRA. However, ¹²³I-IMP SPECT on day 13 showed cortical hypoperfusion which indicated thalamus involvement with neural deactivation. Additionally, 7T-MRA on day 15 revealed an intact left AchA suggesting reperfusion. The neurological deficits improved gradually after treatment and rehabilitation. This case demonstrates AchA infarction with cortical hypoperfusion associated with thalamus involvement, which was clarified by performing ¹²³I-IMP SPECT and 7T-MRA. Perfusion analysis and evaluation of detailed vascular anatomy in stroke can be expected to elucidate pathological conditions