Extra Movements in Healthy People: Challenging the Definition and Diagnostic Practice of Tic Disorders.

The occurrence of motor/vocal tics, that is, "extra movements" and/or "extra vocalizations," is the leading diagnostic criterion for tic disorders. We show that extra movements are common also in healthy controls, so that a surplus of movements per se is not indicative of the presence of a tic disorder. This questions the usefulness of Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for tic disorders in clinical practice. Apparently, it is not solely a surplus of movements that defines tic disorders. Instead, movement characteristics and patterns seem to play a crucial role. ANN NEUROL 2023;93:472-478.

Effect of rescue surgery after non-curative endoscopic resection of early gastric cancer.

BACKGROUND: Whether rescue surgery confers a survival benefit in patients undergoing non-curative endoscopic resection of early gastric cancer remains controversial. METHODS: This was a retrospective review of patients who underwent non-curative endoscopic resection of at least one lesion of differentiated-type early gastric cancer between 2000 and 2011. Patients with a positive lateral resection margin as the only non-curative factor were excluded. Outcome was investigated by univariable (Kaplan-Meier) and multivariable (Cox proportional hazards) analysis. RESULTS: Some 341 patients underwent non-curative endoscopic resection for at least one lesion of differentiated-type early gastric cancer. Sixty-seven patients with a positive lateral resection margin as the only non-curative factor were excluded, leaving 274 patients for analysis; 194 had rescue surgery and 80 had no additional treatment. The median duration of follow-up was 60·5 months. Patients who had rescue surgery were younger, had a lower Charlson co-morbidity index score, smaller tumours and a higher lymphovascular invasion rate than patients with no treatment. Among 194 patients who had rescue surgery, intragastric local residual tumours were found in ten (5·2 per cent) and lymph node metastases in 11 (5·7 per cent). Patients with lymph node metastasis were significantly older than those without metastasis; no other significant differences were found. Univariable analysis showed that patients aged less than 65 years, those with a Charlson co-morbidity index score below 4 and patients undergoing rescue surgery had significantly longer overall survival. Five-year overall survival rates in the rescue surgery and no-treatment groups were 94·3 and 85 per cent respectively. In multivariable analysis, rescue surgery was identified as the only independent predictor of overall survival after non-curative endoscopic resection of early gastric cancer. CONCLUSION: Rescue surgery confers a survival benefit after non-curative endoscopic resection of early gastric cancer.

Feasibility and efficacy of argon plasma coagulation for early esophageal squamous cell neoplasia.

We present 19 cases in which argon plasma coagulation (APC) was used as curative initial treatment for 5 low-grade esophageal squamous intraepithelial neoplasias (ESINs), 12 high-grade ESINs, and 2 early esophageal squamous cell carcinomas (ESCCs). Complete response was defined as the absence of tumor from any biopsy taken from the ablated lesion. At follow-up endoscopy 2 - 4 months after APC, 94.7 % of patients had achieved complete response in a single treatment session. Only one patient with high-grade ESIN showed local recurrence. This patient underwent additional APC and showed complete response at 12 months after initial APC. At the 12-month follow-up endoscopy, again 94.7 % had a complete response. The exception was one patient with local recurrence, who underwent additional APC. After the 12-month follow-up endoscopy, no patient showed local recurrence during a median follow-up of 22 months. No stricture requiring endoscopic dilation occurred after the procedure. This study suggests that APC is a feasible and effective treatment modality for ESIN and early ESCC.

Y-box-binding protein 1 (YB-1) and its functions.

This review describes the structure and functions of Y-box binding protein 1 (YB-1) and its homologs. Interactions of YB-1 with DNA, mRNAs, and proteins are considered. Data on the participation of YB-1 in DNA reparation and transcription, mRNA splicing and translation are systematized. Results on interactions of YB-1 with cytoskeleton components and its possible role in mRNA localization are discussed. Data on intracellular distribution of YB-1, its redistribution between the nucleus and the cytoplasm, and its secretion and extracellular functions are summarized. The effect of YB-1 on cell differentiation, its involvement in extra- and intracellular signaling pathways, and its role in early embryogenesis are described. The mechanisms of regulation of YB-1 expression in the cell are presented. Special attention is paid to the involvement of YB-1 in oncogenic cell transformation, multiple drug resistance, and dissemination of tumors. Both the oncogenic and antioncogenic activities of YB-1 are reviewed. The potential use of YB-1 in diagnostics and therapy as an early cancer marker and a molecular target is discussed.

Proteasome system of protein degradation and processing.

In eukaryotic cells, degradation of most intracellular proteins is realized by proteasomes. The substrates for proteolysis are selected by the fact that the gate to the proteolytic chamber of the proteasome is usually closed, and only proteins carrying a special "label" can get into it. A polyubiquitin chain plays the role of the "label": degradation affects proteins conjugated with a ubiquitin (Ub) chain that consists at minimum of four molecules. Upon entering the proteasome channel, the polypeptide chain of the protein unfolds and stretches along it, being hydrolyzed to short peptides. Ubiquitin per se does not get into the proteasome, but, after destruction of the "labeled" molecule, it is released and labels another molecule. This process has been named "Ub-dependent protein degradation". In this review we systematize current data on the Ub-proteasome system, describe in detail proteasome structure, the ubiquitination system, and the classical ATP/Ub-dependent mechanism of protein degradation, as well as try to focus readers' attention on the existence of alternative mechanisms of proteasomal degradation and processing of proteins. Data on damages of the proteasome system that lead to the development of different diseases are given separately.

Nucleocytoplasmic transport of proteins.

In eukaryotic cells, the movement of macromolecules between the nucleus and cytoplasm occurs through the nuclear pore complex (NPC)--a large protein complex spanning the nuclear envelope. The nuclear transport of proteins is usually mediated by a family of transport receptors known as karyopherins. Karyopherins bind to their cargoes via recognition of nuclear localization signal (NLS) for nuclear import or nuclear export signal (NES) for export to form a transport complex. Its transport through NPC is facilitated by transient interactions between the karyopherins and NPC components. The interactions of karyopherins with their cargoes are regulated by GTPase Ran. In the current review, we describe the NPC structure, NLS, and NES, as well as the model of classic Ran-dependent transport, with special emphasis on existing alternative mechanisms; we also propose a classification of the basic mechanisms of protein transport regulation.

Truncated form of importin alpha identified in breast cancer cell inhibits nuclear import of p53.

Disruption of the function of tumor suppressor proteins occasionally can be dependent on their subcellular localization. In about 40% of the breast cancer tissues, p53 is found in the cytoplasm as opposed to the nucleus, where it resides in normal breast cells. This means that the regulation of subcellular location of p53 is an important mechanism in controlling its function. The transport factors required for the nuclear export of p53 and the mechanisms of their nuclear export have been extensively characterized. However, little is known about the mechanism of nuclear import of p53. p53 contains putative nuclear localization signals (NLSs) which would interact with a nuclear transport factor, importin alpha. In this report we demonstrate that importin alpha binds to NLSI in p53 and mediates the nuclear import of p53. Reverse transcriptase-polymerase chain reaction and sequencing analyses showed that a truncated importin alpha deleted the region encoding the putative NLS-binding domain of p53, suggesting that it could not bind to NLSs of p53 proteins. Binding of importin alpha to p53 was confirmed by using yeast two-hybrid assay. When expressed in CHO-K1 cells, the truncated importin alpha predominantly localized to the cytoplasm. In truncated importin alpha expressing cells, p53 preferentially localized to cytoplasmic sites as well. A significant increase in the p21(waf1/cip1) mRNA level and induction of apoptosis were also observed in importin alpha overexpressing cells. These results strongly suggest that importin alpha functions as a component of the NLS receptor for p53 and mediates nuclear import of p53.

Activating mutation of GS alpha in McCune-Albright syndrome causes skin pigmentation by tyrosinase gene activation on affected melanocytes.

McCune-Albright syndrome (MAS) is a sporadic disease characterized by café-au-lait spots, polyostotic fibrous dysplasia and hyperfunctional endocrinopathies. To elucidate the mechanism of skin pigmentation, melanocytes, keratinocytes and fibroblasts were primary cultured from the café-au-lait spot of a MAS patient. Then, mutational analysis and morphologic evaluation were performed. Also, cAMP level and tyrosinase gene expression in cultured cells were determined. Only Gsalpha mutation was found in affected melanocytes and the cAMP level in affected melanocytes was higher than that of normal melanocytes. The mRNA expression of tyrosinase gene was increased in the affected melanocytes. This study suggests that skin pigmentation of MAS results from activating mutation of Gsalpha in melanocytes and the mechanism involves the c-AMP-mediated tyrosinase gene activation.

[Homocarnosine levels in repeated hypothermia and hibernation]. / Soderzhanie gomokarnozina pri mnogokratnoi gipotermii i zimnei spiachke.

Compulsory cooling of rats (20 degrees) and susliks (20 degrees-10 degrees) leads to a considerable decrease of homocarnosine in cerebral hemispheres in midbrain and diencephalon and cerebellum. When hypothermia is repeated 4 or 7 times (in every 24 h) a more considerable decrease in the homocarnosine quantity in the rat brain takes place and it is not normalized after self-warming of the organism. After 11-12-fold hypothermia, when a certain adaptation of animals to cooling is developed, the second increase of homocarnosine content with subsequent normalization of its level in great cerebral hemispheres and in cerebellum at self-warming is observed. In dynamics of the hibernation (1, 7 and 30 days) either preservation of normothermal level or a certain increase of the homocarnosine content in all areas of the suslik brain under examination is observed.