海邊來的鄉下人

這是關於一篇新聞，卻真真實實的代表了好幾個辛苦的家庭…..

罕見疾病當中，有一部分患者是因為細胞的生化代謝過程中有某個環節出錯而導致代謝異常的產物在身體裡面堆積而導致患者身體異常甚而危及生命。這種因為遺傳異常導致的疾病如果發生率越小，病患的族群就越少，在醫學上的研究與治療也就越困難，當然，病患人數少通常也表示藥品的市場小，在新藥開發與臨床試驗的高成本下，藥廠通常也不會輕易將資源投注在罕見疾病的用藥開發上！這也就是我們所稱的”孤兒藥”。由此，我們不難想像這類病患與患者家屬的處境有多艱難，電影羅倫佐的油所講述的就是這種家庭所面臨的艱困。

Niemann-Pick disease又稱「尼曼匹克症」，同樣是脂質代謝異常遺傳疾病的一種，這是由於sphingomyelin在細胞中出現不正常堆積現象所造成的疾病，正常情況下sphingomyelin是構成神經細胞膜的重要物質之一，屬於sphingolipids的一種，也就是一種phospolipids，是由sphingomyelin synthase將phosphatidylcholine上面的phosphorylcholine接到ceramide所構成的【註一】。而sphingomyelinase就是分解sphingomyelin的酵素，一但sphingomyelinase缺乏過量的sphingomyelin就會累積於病人的肝臟、腎臟、脾臟、骨髓、腦部，造成器官的病變，症狀會陸續出現吞嚥困難、走路跌倒、腦部功能退化，最後會逐漸成為植物人、死亡。

Niemann-Pick disease主要分為A、B、C三種型別【註二】，近來醫學界亦陸陸續續發現其他如D、E、F的型別，全世界患者不到一百人，大多數患者為Ａ型，主要罹病族群多具猶太人血統，在台灣的Niemann-Pick disease患者不超過十名，以Ｃ型居多，大約有95%的患者是NPC1基因突變造成，這類患者累積的物質為細胞不能代謝的膽固醇，發病時間約七至十三歲。

由於這種遺傳疾病是由體染熱體的變異所引起的隱性遺傳，父母雙方各帶一相同的缺陷基因，每一胎皆有四分之一的機率罹患此症【註三】，家族中有病例者婚前應該接受基因篩檢以避免新生兒疾病。目前Niemann-Pick disease尚無治癒的方法，只有ZAVESCA這種臨床試驗中的新藥可以讓患者停止退化，甚至恢復吞嚥功能，但就如我先前所敘述的，這類孤兒藥不易取得且要價非常高，不是一般家庭負擔的起的，目前國建局已經終止了對這類藥物的補助，這群小朋友有正面臨無藥可醫的窘迫。大家在百貨公司週年慶血拼之餘，請想想這群可憐的小朋友，可以電洽台大醫院的社服（02）2356-2097了解詳情，或是劃撥給「台大醫院社會服務部」劃撥帳號00145791，註明捐款給尼曼匹克症病患。有錢出錢沒錢轉貼喔~~~

【註一】The sphingomyelins are synthesized by the transfer of phosphorylcholine from phosphatidylcholine to a ceramide in a reaction catalyzed by sphingomyelin synthase. Sphingomyelins are sphingolipids that are also phospholipids. Sphingomyelins are important structural lipid components of nerve cell membranes. The predominant sphingomyelins contain palmitic or stearic acid N-acylated at carbon 2 of sphingosine. (I'll attach the figure as soon as possible!)

【註二】Both of Niemann-Pick disease type A and type B, insufficient activity of an enzyme called sphingomyelinase causes the build up of toxic amounts of sphingomyelin, a fatty substance present in every cell of the body. Type A is the most common type, which occurs in infants. It is characterized by jaundice, an enlarged liver, and profound brain damage. Children with this type rarely live beyond 18 months. Type B involves an enlarged liver and spleen, which usually occurs in the pre-teen years. The brain is not affected. Niemann-Pick Type C (NPC) is very different than Type A or B.  NPC Patients are not able to metabolize cholesterol and other lipids properly within the cell. Types C is characterized by a defect that disrupts the transport of cholesterol between brain cells.Affected individuals have only moderate enlargement of the spleen and liver, but brain damage may be extensive and cause an inability to look up and down, difficulty in walking and swallowing, and progressive loss of vision and hearing.

【註三】

參考網址:

1.      羅倫佐的油

2.      ZAVESCA救退化 醫師：沒更好的藥

3.      財團法人罕見疾病基金會

4.      How Is Niemann-Pick Disease Inherited? 

5.      National NPD foundation

6.      Zavesca Information from Drugs.com

Many people have a temporary spell, often in early afternoon. But I feel drowsy all the time and always have desire for a nap. I can’t help to consider whether I am the potential excessive daytime sleepiness or not. How to diagnosis excessive daytime sleepiness? What will cause this symptom? And is there any effective treatment? Am I the potential dire person of falling asleep unintentionally or at inappropriate times?

The reasons of daytime sleepiness are including volitional sleep deprivation, obstructive apnea, and Narcolepsy. Narcolepsy occurs due to the part of the brain which regulates sleep and wakefulness can’t function well. The symptoms generally begin between the ages of 15 and 30. I found the classical symptoms of Narcolepsy below:

1.Excessive daytime sleepiness.

2.      2.Cataplexy: a striking, sudden episode of muscle weakness triggered by high emotions. Typically, the patient's knees buckle and may give way upon laughing, elation, fear, surprise or anger. In other typical cataplectic attacks the head may drop or the jaw may become slack. In severe cases, the patient might fall down and become completely paralysed for a few seconds to several minutes. Reflexes are abolished during the attack.

3.      3.Sleep paralysis: the patient suddenly finds himself unable to move for a few minutes, most often upon falling asleep or waking up.

4.      4.Hypnagogic hallucinations: dream-like auditory or visual hallucinations, while dozing or falling asleep

Fortunately, it seems that I do not have typical symptoms of narcolepsy. Maybe my daytime sleepiness is just because my desiring to sleep all day….. There are some articles about “Narcolepsy” on the internet net, such as….

Symptoms of Narcolepst-Stanford school of medicine

Narcolepsy-Brain Australia

看到新聞，覺得這招不錯用......

英格蘭北部切斯特動物園一隻科莫多蜥蜴處女生子，孵化期就在耶誕節前後。雌蜥蜴富蘿拉未交配而生蛋，並非天大怪事，但那些蛋通常未經授精，不會發育成胚胎。但富羅拉的這些未授精的蛋孵化出的胚胎 DNA都是富蘿拉的，她有七個寶寶即將破殼而出。

未經雄性授精的處女生殖，科學名詞叫「孤雌生殖」，包括爬蟲類以及魚、黃蜂、芽蟲在內，自然界約70個物種有此現象，但科莫多雌蜥蜴自己產卵兼授精，一身兼為父母，卻是科學界首見。

這說明科莫多蜥蜴可以孤雌生殖，也可以兩性生殖，「找不到男朋友，就自己想辦法」！

生物晶片自1980年代發展至今已經隨著時代的進步與技術的成熟而成為基礎研究必備的強勢操作平台。Affymetrix應用半導體產業技術的光化學技術(光罩法)，製作高密度的GeneChip而成功擠身生物晶片產業的龍頭。而利用Affymetrix產品所發表的文獻也累積了近萬篇，足見這項技術被研究領域肯定的程度與Affymetrix的貢獻。

截至目前為止，Affymetrix仍是將DNA微陣列技術縮小在最小點位（Feature size）的領跑者。但Affymetrix仍不滿足於現況，一方面因為Agilent等競爭對手切割將近一半原本由Affymetrix壟斷的生物晶片市場，而讓Affymetrix備感壓力。另一方面近年生物資訊的分析開始統合，學術研究逐漸把焦點轉回功能分析，這使得將生物晶片這種大量且快速執行分析的工具應用在生物功能性檢測的需求越來越大。也因此，在推Gene expression array之後Affymetrix推出能檢測基因個別Exon與完整偵測whole genome的Exon array與Tiling array。

1.      Exon array：
Exon array設計的原理是在基因的每個Exon上各設計四個primer sites，相較於只能偵測基因備表現與否的3’-Array，Exon array除了可以偵測基因的表現外，更可以得知不同Exon的表現情形。這款探討alternative splicing的產品被用來研究組織的發育、RNA表現相關疾病與基因的變異等。

          為了證明我不只是會對帥哥流口水，同時也是對學術研究有熱誠的好孩子，再加上維基百科的解釋實在是糟透了，讓我弟看不懂跑來問我！今晚來討論一下讓帥哥教授Craig C. Mello得到諾貝爾獎的研究：gene silencing by double-stranded RNA。

          首先，要先了解生命科學界赫赫有名的理論：The central dogma。每個人都曾經被問過自己是像爸爸或是像媽媽，而我們之所以會和血親相像的原因是因為有個重要的東西在記錄著我們生命的密碼，那就是DNA。而DNA上紀錄的訊息中，可以被解讀、具有功能的則稱之為基因，主角” RNAi”就是調控基因表現的其中一個方法。

Disease characteristics.  Familial lipoprotein lipase (LPL) deficiency is characterized by increased plasma trigylceride concentration caused by delayed clearance of chylomicrons from the plasma after digestion of dietary fat. Affected individuals have childhood-onset episodic abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly. Symptoms resolve with restriction of dietary fat to 20 grams/day or less.

Diagnosis/testing.  Familial LPL deficiency is caused by very low or absent activity of LPL encoded by the gene LPL. The diagnosis of familial LPL deficiency is based on the assay of LPL activity in plasma following intravenous administration of heparin. Detection of very low or absent LPL activity in an assay system that contains either normal plasma or apoprotein C-II and excludes hepatic lipase is diagnostic of familial LPL deficiency.

近日整理兼職翻譯的文章……發現有許多好東西…...想起剛開始翻譯的生澀……謝謝當初孟德爾生技的總經理Belinda Chen給我這麼好的機會….甘溫喔~~~