シュウハスウ アッシュク ヘンカンガタ ホチョウキ ノ コウカ ニツイテ

近年の補聴技術の進歩により、補聴器適用対象となる患者の範囲も広がってきたが、 高音急墜型、皿型、低温障害方の感音性難聴者など、いまだに補聴器適合（フィッティン グ）が困難な症例も多い。そのうちでも、低温部にのみ残聴のある感音性難聴者に対する 補聴器のフィッティングは極めて困難で、従来型補聴器では語音明瞭度の改善が得られな い。語音弁別のための手がかりは、広い周波数帯域に分布しているとされ、この手がかり がキュー（cue）と呼ばれている。低音部のみに残聴のある患者では、高音域の聴力レベ ルがオージオメータの最大出力でも検査音を聴取できない状態（スケールアウト）である 場合が多く、補聴器を用いて高音域を増幅しても高音域に含まれるキューの情報がまった く入らないことが多い。したがって、語音明瞭度の改善が得られないと考えられている。 近年、コンピュータ技術を用いて、伸長増幅や圧縮増幅を行う補聴器が次々と開発され ている。そのひとつに、周波数圧縮変換型補聴器（AVR社製FT-40 MK-2、トランソニッ ク）がある。これは、低周波帯域のスペクトルは圧縮せず、高周波帯域のスペクトルを大 きく圧縮し、低音部はそのままの周波数で、高音部を低音部の残聴域にシフトする、いわ ゆる非線形スペクトル圧縮の原理を応用した補聴器である。この補聴器は、従来型補聴器 では、フィッテイングがきわめて困難であった、低音部のみに残聴のある感音性難聴者を対象 として開発されたものである。先天性感音難聴児に装用させると、聴覚の認識、言語獲得 の観点から従来の補聴器と人工内耳の中間に位置づけられるという報告や、後天性難聴者 において無声子音の語音明瞭度の改善が認められたという報告はあるが、実際には、難聴 者に対するトランソニック補聴効果の評価は一定していない。そこで、本研究では、トラ ンソニックの効果を検討するため、低音部のみに残聴のある感音性難聴者3例に対しトラ ンソニック補聴器を装用させ、語音の種類別の明瞭度の検討を行った。低音部のみに残聴 のある感音性難聴者の頻度は非常に低く、著者らの施設では過去3年間に3例の症例が検討 できたのみである。ゆえに、低音部のみに残聴のある感音性難聴者を数多くそろえてト ランソニックの効果を検討することは不可能に近い。そこで、正常者21例において、低 音部のみに残聴のある感音性難聴を低減濾波器を用いてシミュレートし、トランソニック の使用が、どの程度語音明瞭度の改善に対して効果があるのかについても検討した。 その結果、患者および難聴シミュレート例ともに、トランソニック使用直後では語音明瞭度 の改善は得られなかったが、トランソニック装用下での訓練により一部で著名な改善を 認めた。患者においては、無声子音（なかでも特に/S/）や有声閉鎖音（/z/など）、 鼻音（/n/など）の明瞭度が改善された。難聴をシミュレートした例でも母音、/s/、/k/、/t/、 /n/で語音明瞭度が改善しており、これらを含む57S語表中の全ての単音節での検討におい ても語音明瞭度が改善した。これらの訓練によって得られる語音明瞭度の改善は、トラン ソニックにより高音部に存在するキューが低音部に圧縮変換され、新たなキューとして認知 できるようになったためと考えられる。正常者でシミュレートした難聴は、実際の感音 性難聴を完全に実現できるわけではないが、同程度の難聴を多数作成することが可能であ り、補聴器の効果を検討するためには、有用な研究手段となると考えられた

Effectiveness of a frequency transposing hearing aid

The effectiveness of a frequency transposing hearing aid (Transonic) was investigated in three patients with severe sensorineural hearing loss and 21 normal controls. All the patients had residual hearing only in low frequency. Severe middle-high frequency sensorineural hearing loss model was reproduced in the 21 normal controls. Little improvement was seen in the articulation scores of these patients and the 21 controls at the first use of Transonic. However, after two weeks auditory training, significant improvement was seen in some speech sounds. In the three patients, the articulation scores of voiceless consonants, in particular/s/, voiced plosives, voiced fricatives and nasal sounds were improved. In the controls, the articulation scores of vowels and consonants such as /s/, /k/, /t/, /n/ were improved. Improvements in articulation scores by this type of training could be explained as follows : with the use of Transonic, speech cues in the high frequency area were transposed to new recognizable cues in the low frequency region. Sensorineural hearing loss model in normal controls was not the same as actual sensorineural hearing loss, but it was possible to experimentally induce comparable deafness in many individuals. As a result, they could serve as good subjects when investigating the effectiveness of hearing aids

後筋筋電図法

The posterior cricoarytenoid muscle (PCA) is the major laryngeal vocal cord abductor, and electromyography (EMG) of this muscle plays an important role in investigating the mechanism of speech and respiration. However, the EMG study of this muscle has been limited, because it's location makes it difficult to record a signal from the muscle. Different PCA recording techniques have been developed. The approach to the muscle developed along three main lines: per oral, percutaneous and per nasal approach. Three kinds of electrodes; a bipolar needle electrode, a surface electrode and a hooked wire electrode have been used for the recording. Techniques of electrode placement in the PCA are reviewed

Up-regulation of stanniocalcin 1 expression by 1,25-dihydroxy vitamin D3 and parathyroid hormone in renal proximal tubular cells

Stanniocalcin 1 and stanniocalcin 2 are two glycoprotein hormones, which act as calcium phosphate-regulating factor on intestine and kidney. We have previously reported that stanniocalcin 2 expression is positively and negatively controlled by 1,25(OH)2D3 and parathyroid hormone in renal proximal tubular cells. However, it has been unclear whether they regulate the stanniocalcin 1 gene expression. In this study, we identified the opossum stanniocalcin 1 cDNA sequence. The opossum stanniocalcin 1 amino acid sequence had 83% homology with human stanniocalcin 1, and has a conserved putative N-linked glycosylation site. Real-time PCR analysis using opossum kidney proximal tubular (OK-P) cells revealed that the mRNA levels of stanniocalcin 1 gene is up-regulated by both 1,25(OH)2D3 and parathyroid hormone in dose-dependent and time-dependent manners. We also demonstrated that the stanniocalcin 1 expression was increased in parathyroid hormone injected rat kidney. Furthermore, the mRNA expression of stanniocalcin 1 and stanniocalcin 2 were oppositely regulated by phorbol 12,13-myristic acetate, a specific PKC activator. Interestingly, the up-regulation of stanniocalcin 1 gene by 1,25(OH)2D3 and phorbol 12,13-myristic acetate were not prevented in the presence of actinomycin D, an RNA synthesis inhibitor. These results suggest that the stanniocalcin 1 gene expression is up-regulated by 1,25(OH)2D3 and parathyroid hormone through mRNA stabilization in renal proximal tubular cells

喉頭ストロボスコピー所見の定量的評価

A computer system was introduced for quantitative evaluation of laryngeal images in normal volunteers and laryngeal paralysis patients. The subjects consisted of 10 normal volunteers and 10 patients with unilateral laryngeal paralysis (5 median fixation cases and 5 paramedian fixation cases). For phonatory examination, the sustained vowel /e/ with an easy phonation level was used. A glottal area was measured in digitized laryngeal stroboscopic images and normalized by the square of the vocal fold length. The average glottal area was defined to be as the average of the maximum and the minimum normalized glottal areas. In laryngeal paralysis patients, the average glottal area became larger as the paralyzed vocal fold position deviated from the median. Furthermore, the observation methods for vocal fold vibration was reveiwed and discussed. It emphasized that laryngeal stroboscopy was the most useful clinical testing methods

Regulation of Npt2b gene promoter activity by RAR/RXR-C/EBP

Inorganic phosphate (Pi) homeostasis is regulated by intestinal absorption via type II sodium-dependent co-transporter (Npt2b) and by renal reabsorption via Npt2a and Npt2c. Although we previously reported that vitamin A-deficient (VAD) rats had increased urine Pi excretion through the decreased renal expression of Npt2a and Npt2c, the effect of vitamin A on the intestinal Npt2b expression remains unclear. In this study, we investigated the effects of treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, on the Pi absorption and the Npt2b expression in the intestine of VAD rats, as well as and the underlying molecular mechanisms. In VAD rats, the intestinal Pi uptake activity and the expression of Npt2b were increased, but were reduced by the administration of ATRA. The transcriptional activity of reporter plasmid containing the promoter region of the rat Npt2b gene was reduced by ATRA in NIH3T3 cells overexpressing retinoic acid receptor (RAR) and retinoid X receptor (RXR). On the other hand, CCAAT/enhancer-binding proteins (C/EBP) induced transcriptional activity of the Npt2b gene. Knockdown of the C/EBP gene and a mutation analysis of the C/EBP responsible element in the Npt2b gene promoter indicated that C/EBP plays a pivotal role in the regulation of Npt2b gene transcriptional activity by ATRA. EMSA revealed that the RAR/RXR complex inhibits binding of C/EBP to Npt2 b gene promoter. Together, these results suggest that ATRA may reduce the intestinal Pi uptake by preventing C/EBP activation of the intestinal Npt2b gene

NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts

Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) homologues have been suggested to regulate osteoclast differentiation. However, no bone abnormalities have been documented in Nox1 deficient, Nox2 deficient, or Nox3 mutant mice. During receptor activator of nuclear factor-κB ligand (RANKL)-stimulated differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts, mRNA levels of Nox enzymes (Nox1-4) and their adaptor proteins were monitored by real-time reverse transcriptase PCR. RAW264.7 cells constitutively expressed abundant Nox2 mRNA and small amounts of Nox1 and Nox3 transcripts. RANKL markedly attenuated Nox2 mRNA expression in association with reciprocal up-regulation of Nox1 and Nox3 transcripts. Introduction of small interference RNA targeting p67phox or p22phox into RAW264.7 cells effectively downregulated ROS generation and significantly suppressed the RANKL-stimulated differentiation, which was assessed by appearance of tartrate resistant acid phosphatase (TRAP)- positive, multinucleated cells having an ability to form resorption pits on calcium phosphate thin film-coated disks, and by expression of osteoclast marker genes (TRAP, cathepsin K, Atp6i, ClC-7, and NFATc1). Our results suggest that RANKL may stimulate switching between Nox homologues during osteoclast differentiation, and Nox-derived ROS may be crucial for RANKL-induced osteoclast differentiation

stearoyl-CoA desaturaseの低下は慢性腎臓病における過剰な小胞体ストレスを介して筋萎縮に寄与する

Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD

ビタミンDの必要量，疾患および代謝調節機構について

In chronic renal failure patients and dialysis patients, hyperphosphatemia and hypovitaminosis occur due to impaired urinary phosphorus excretion and vitamin D activation, leading to secondary hyperparathyroidism and renal osteodystrophy.These events can lead to severe ectopic calcification in blood vessels and the heart, increasing the risk of cardiovascular disease and death.In recent years, approximately half of patients undergoing dialysis have diabetes, so it is important to prevent the progression to diabetic nephropathy as one of the three major complications. Furthermore, it has been reported that hyperphosphatemia increases the risk of developing heart failure and death even when renal function is normal, and blood concentrations of phosphorus and 1，25（OH）2D, the active form of vitamin D, have a circadian rhythm. Therefore, quantitative, qualitative, and temporal nutritional management of dietary phosphorus during a wide range of life stages from healthy to disease is important for maintaining homeostasis of vitamin D, calcium, and bone metabolism, and for preventing the onset and progression of kidney disease, not only is it useful, but it is also thought to be useful in preventing lifestyle-related diseases such as diabetes and inflammatory diseases from becoming more severe. In this article, we will discuss vitamin D deficiency/insufficiency in renal disease, its relationship with circadian rhythms, energy and cholesterol metabolism revealed through research on the regulation of vitamin D metabolism, differences in phosphorus sensitivity at life stages