황사랑
From Biocourse
1. Search the NCBI database for sickle cell anemia. What can you tell me about it?
1. Hydroxyurea reduces the frequency of acute pain in sickle cell disease (SCD).
Patients suffering from sickle cell disease show an increased ischemic intolerance due to continuous pro-inflammatory activation and dysfunction of the endothelium by recurrent vaso-occlusive episodes.
The presented case shows the manifestation of a postoperative compartment syndrome of the lower leg following the intraoperative use of blood arrest in a patient with previously unknown sickle cell disease.
Paclitaxel-induced sickle cell crisis.
Butler University College of Pharmacy and Health Sciences, Indianapolis, IN, USA. nwilson25@butler.edu
PURPOSE: A case of paclitaxel-induced painful crisis in a patient with breast cancer and hemoglobin sickle cell disease (SCD) is reported. SUMMARY: A 55-year-old postmenopausal African-American woman had stage IIB invasive ductal carcinoma of the left breast. She was not taking any medications and did not report a history of cancer or other diseases. She had mild microcytic anemia, but the rest of her blood counts and liver function test values were normal. Bone scans and computed tomography scans of her chest and abdomen did not reveal any metastatic disease. She underwent a routine left segmental mastectomy and axillary lymph node dissection that revealed a 4-cm invasive cancer with 1 of 10 axillary lymph nodes positive for metastatic disease. Her treatment plan included chemotherapy with weekly paclitaxel, followed by fluorouracil, epirubicin, and cyclophosphamide and radiation. The first cycle of paclitaxel was well tolerated until one week after initiation when the patient woke up in the middle of the night with a sudden onset of excruciating back pain and muscle spasms. Other symptoms that developed included fatigue, left-sided rib pain, and shortness of breath. The patient recalled being told that she had sickle cell trait but said that she never had a sickle cell crisis. Laboratory tests during her 13-day hospitalization revealed hemolysis. The patient was diagnosed with hemoglobin SCD and later discharged with as-needed, low-dose oxycodone and baclofen, antibiotics, and folic acid. CONCLUSION: A patient with breast cancer and SCD had a painful crisis after receiving paclitaxel as part of her chemotherapy regimen.
PMID: 18593679 [PubMed - in process]
2. What causes beta-zero-thalassemia?
There is a 25% change of having a baby with sickle beta zero thalassemia with each pregnancy
베타지중해빈혈
베타글로빈 유전자의 돌연변이에 의하여 베타글로빈쇄의 생성이 감소하여 발생
우리나라에서도 이제 철결핍성 빈혈이 아닌 소구성 빈혈의 진단시 감별하여야 하는 질환
베타 지중해빈혈의 돌연변이는 베타글로빈 유전자 전체에 넓게 분포
돌연변이가 집중적으로 몰려있는 부위는 없다
이렇게 돌연변이가 유전자 전체에 걸쳐 넓은 지역에서 발생하는 유전질환의 경우, 유전자의 어느 부분에 돌연변이가 있는 지를 조사하는 돌연변이 검색이 필요
정상 헤모글로빈과 겸상적혈구 헤모글로빈은 146개의 아미노산으로 구성된 헤모글로빈 β사슬에서 단 한 개의 아미노산이 다르다. 이는 정상적으로 있어야 할 6번째 아미노산인 글루탐산(Glutamic acid)의 유전암호 GAG가 발린(Valine)의 유전암호인 GTG로 바뀌었기 때문이다.그 결과 정상 적혈구는 원반 모양이지만, 겸상적혈구는 헤모글로빈 분자가 쉽게 막대 형태로 결정화되어 적혈구가 낫 모양으로 변형된다
Sickle Beta Zero Thalassemia (sickle BA-ta zero thal-a-SEE-me-a) is similar to sickle cell anemia. Your child's red blood cells contain an abnormal hemoglobin, called hemoglobin S or sickle hemoglobin. In addition, the red blood cells have a defect called thalassemia, which results in cells that are small in size and more pale than usual.
Instead of appearing round or donut shaped, your child's red blood cells are somewhat small, pale, and misshapen. Some may appear sickled or banana shaped.
Because sickle beta zero thalassemia is inherited, it is a lifelong disorder. There is no treatment or cure. Your child will always have a mild anemia or slightly low blood count. This may result in occasional tiredness or weakness.
3. Sickle hemoglobin is a "point mutation" meaning only one nucleic acid is exchanged resulting in sickle cell anemia. Which nucleic acid is exchanged?
Adenine(A) in normal hemoglobin is replaced with Thymine(T) is sickle hemoglobin.
4. How does this single nucleic acid exchange cause such a deadly disease?
글루탐산이 발린으로 바뀌면서 헤모글로빈의 용해도가 떨어지며, 산소가 낮게 되면 돌연변이 형태의 헤모글로빈 단백질은 긴 체인을 형성하여 적혈구 세포를 도넛 모양이 아닌 초승달 모양으로 바꾸어 버린다.
