Successful Treatment with Clonazepam and Pramipexole of a Patient with Sleep-Related Eating Disorder Associated with Restless Legs Syndrome: A Case Report

Sleep-related eating disorder (SRED) is characterized by recurrent episodes of involuntary eating during sleep period and is often associated with restless legs syndrome (RLS). Although pharmacotherapy is recommended for SRED patients, no drug have shown promising effects so far. The patient, a 48-year-old Japanese housewife, first visited our clinic and complained about nighttime eating. She had a history of hypertension, diabetes mellitus, sleep apnea syndrome, and depression. Insomnia appeared 10 years before the first visit and she often received hypnosedatives; at the same time, she developed nocturnal eating episodes. She had amnesia for these episodes, and she felt urge to move her legs while sleeping. The patient was diagnosed with SRED and RLS. Reduction in the doses of triazolam decreased her nighttime eating frequency, and her complete amnesia changed to vague recall of eating during night. Clonazepam 1.0 mg at bedtime decreased nocturnal eating frequency from 1 to 2 times per month, though sleepwalking remained. Administration of pramipexole 0.125 mg relieved all symptoms including SRED, RLS, and sleepwalking. This is the first paper to report that the combination of clonazepam and pramipexole therapy-reduced SRED episodes and RLS symptoms

Microenvironment and radiation therapy

Dependency on tumor oxygenation is one of the major features of radiation therapy and this has led many radiation biologists and oncologists to focus on tumor hypoxia. The first approach to overcome tumor hypoxia was to improve tumor oxygenation by increasing oxygen delivery and a subsequent approach was the use of radiosensitizers in combination with radiation therapy. Clinical use of some of these approaches was promising, but they are not widely used due to several limitations. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that is activated by hypoxia and induces the expression of various genes related to the adaptation of cellular metabolism to hypoxia, invasion and metastasis of cancer cells and angiogenesis, and so forth. HIF-1 is a potent target to enhance the therapeutic effects of radiation therapy. Another approach is antiangiogenic therapy. The combination with radiation therapy is promising, but several factors including surrogate markers, timing and duration, and so forth have to be optimized before introducing it into clinics. In this review, we examined how the tumor microenvironment influences the effects of radiation and how we can enhance the antitumor effects of radiation therapy by modifying the tumor microenvironment

Operative approach for multiple primary lung carcinomas

AbstractOf 908 patients who underwent operation for primary lung cancer between January 1985 and June 1996, we considered 57 (6.3%) to have a second primary lung cancer, which was synchronous in 28 cases (3.1%) and metachronous in 29 cases (3.2%). Five-year survival for patients with synchronous and metachronous disease from initial treatment of cancer was 70.3% and 66.0%, respectively. Survival after the development of a metachronous lesion was 32.9% at 5 years. Sixteen of the synchronous second tumors (57%) were detected on preoperative radiography or bronchoscopy and 11 (39%) at the time of operation. Survival of patients at stage I or II from treatment of a synchronous lesion (p = 0.002) and of a metachronous second lesion (p = 0.028) was significantly better compared with those at stage III or IV. Therefore it is important to carefully examine a synchronous lesion before and during the operation of a primary lung cancer and to perform close follow-up surveillance for early detection of a metachronous lesion. In treating multiple lung carcinomas consideration should always be given to performing precise staging, aggressive operative approach for early stage, and oncologically sound parenchymal sparing procedures. (J Thorac Cardiovasc Surg 1998;115:836-40

Pharmacological inhibition of sodium-calcium exchange activates NADPH oxidase and induces infection-independent NETotic cell death

In addition to its function of innate immunity against invading pathogens, neutrophil extracellular traps (NETs) promote thrombosis, autoimmune disease, and cancer metastasis; therefore, unnecessary exposure to the triggers of infection-independent NET generation should be avoided. We herein show that inhibition of forward-mode Na⁺/Ca²⁺ exchange by amiloride analogs, 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and 5-(N-Methyl-N-isobutyl)amiloride (MIA), triggers NETotic cell death independently of infectious stimuli. Isolated human neutrophils treated with EIPA and MIA undergo NETotic cell death by an increase of intracellular Ca²⁺ following activation of NADPH oxidase and the resultant upregulation of intracellular ROS. EIPA- and MIA-mediated intracellular Ca²⁺ increase is attributed to the competitive binding of EIPA and MIA against Na⁺ to Na⁺/Ca²⁺ exchanger 1 (NCX1). These results demonstrate a new mechanism of infection-independent NET generation and implicate NCX1 as a physiologic regulator of intracellular calcium balance and NETotic cell death

Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4.

In addition to its well-known role as a crosslinker of actin filaments at focal-adhesion sites, actinin-4 is known to be localized to the nucleus. In this study, we reveal the molecular mechanism underlying nuclear localization of actinin-4 and its novel interactions with transcriptional regulators. We found that actinin-4 is imported into the nucleus through the nuclear pore complex in an importin-independent manner and is exported by the chromosome region maintenance-1 (CRM1)-dependent pathway. Nuclear actinin-4 levels were significantly increased in the late G2 phase of the cell cycle and were decreased in the G1 phase, suggesting that active release from the actin cytoskeleton was responsible for increased nuclear actinin-4 in late G2. Nuclear actinin-4 was found to interact with the INO80 chromatin-remodeling complex. It also directs the expression of a subset of cell-cycle-related genes and interacts with the upstream-binding factor (UBF)-dependent rRNA transcriptional machinery in the M phase. These findings provide molecular mechanisms for both nucleocytoplasmic shuttling of proteins that do not contain a nuclear-localization signal and cell-cycle-dependent gene regulation that reflects morphological changes in the cytoskeleton

Nucleocytoplasmic Shuttling of Cytoskeletal Proteins: Molecular Mechanism and Biological Significance

Various nuclear functional complexes contain cytoskeletal proteins as regulatory subunits; for example, nuclear actin participates in transcriptional complexes, and actin-related proteins are integral to chromatin remodeling complexes. Nuclear complexes such as these are involved in both basal and adaptive nuclear functions. In addition to nuclear import via classical nuclear transport pathways or passive diffusion, some large cytoskeletal proteins spontaneously migrate into the nucleus in a karyopherin-independent manner. The balance of nucleocytoplasmic distribution of such proteins can be altered by several factors, such as import versus export, or capture and release by complexes. The resulting accumulation or depletion of the nuclear populations thereby enhances or attenuates their nuclear functions. We propose that such molecular dynamics constitute a form of cytoskeleton-modulated regulation of nuclear functions which is mediated by the translocation of cytoskeletal components in and out of the nucleus

Preliminary Report of the Waseda University Excavations at Dahshur North:Tenth Season,2004-2005

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Closure of multiple ventricular septal defects by the felt sandwich technique: Further analysis of 36 patients

ObjectivesWe previously described a novel technique for closure of trabecular ventricular septal defects by sandwiching the septum with 2 polyester felt patches without requiring left ventriculotomy. We describe the midterm results of this technique and the postoperative cardiac function.MethodsThis is a retrospective study of 36 consecutive patients. The median age and body weight at the time of repair was 15 months (range: 2-115 months) and 7.8 kg (range: 3.9-51.9 kg), respectively.ResultsSixty-three trabecular ventricular septal defects in 36 patients were closed with the felt sandwich technique. In the early postoperative period, 1 patient died of pulmonary hypertensive crisis. There were 2 late deaths. One patient died of pneumonia 6 months after surgery, and another died suddenly of ventricular arrhythmias 2 years after surgery. Three patients required reoperation (closure of major residual ventricular septal defect, cardiac transplantation for dilated cardiomyopathy, and pacemaker implantation for complete atrioventricular block). Postoperative left ventricular fractional shortening in the group with a body surface area less than 0.4 m2 was significantly lower than that in the group with a body surface area of 0.4 m2 or greater (0.22 ± 0.09 vs 0.31 ± 0.06, P = .0027). Moreover, there was a strong correlation between postoperative left ventricular ejection fraction and total patch area/body surface area ratio (R = −0.74, P = .0004).ConclusionMultiple trabecular ventricular septal defects can be closed with the felt sandwich technique easily and safely. Although this technique can be used in small infants, the use of numerous felt patches disturbs the movement of ventricular septum, which may cause postoperative cardiac dysfunction