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Hasil Pencarian

Ditemukan 17 dokumen yang sesuai dengan query
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Tita Yuningsih
"Selama oogenesis, oosit tumbuh dalam ukuran dan memperoleh kompetensi pematangannya. Kompetensi pematangan oosit sangat diperlukan untuk mendukung terjadinya fertilisasi dan perkembangan embrio berkualitas baik. Ketidakmampuan untuk menentukan oosit yang berpotensi menghasilkan embrio yang viable masih menjadi kendala utama pada proses Fertilisasi In Vitro (FIV). Penelitian ini bertujuan mengetahui apakah ukuran diameter oosit bisa menjadi prediktor kualitas oosit dan embrio. Penelitian ini menggunakan desain penelitian prospektif cohort. Metode penelitian untuk pengukuran diameter oosit menggunakan aplikasi Image J, setiap oosit dan sel granulosa dikelompokkan sesuai ukuran diameter oosit, oosit dilakukan fertilisasi dengan teknik ICSI/IMSI kemudian diikuti perkembangan embrio sampai hari ke-5. Pemeriksaan ELISA dipakai untuk mengkonfirmasi kualitas oosit dengan melihat kadar protein Akt dan total Akt pada sel granulosa kumulus oosit, sedangkan untuk mengkonfirmasi kualitas embrio adalah dengan melihat parameter morfokinetik embrio, pencapaian blastokista dan frekuensi abnormalitas pembelahan. Hasil penelitian menunjukkan tidak ada perbedaan signifikan (P>0,05) pada kadar protein p-Akt dan total Akt sel granulosa kumulus antara ketiga kelompok. Selain itu pengamatan morfokinetik embrio menunjukkan tidak ada perbedaan signifikan (P>0.05) kecuali parameter S2, begitu pula dengan pencapaian blastokista serta frekuensi abnormalitas pembelahan kecuali parameter reverse cleavage (RC). Kesimpulan yang didapat dari penelitian ini adalah ukuran diameter oosit tidak mempengaruhi kualitas oosit dan embrio. Ukuran diameter oosit tidak bisa menjadi prediktor kualitas oosit dan embrio, karena tidak ada perbedaan signifikan pada kualitas oosit dan embrio ketiga kelompok. Oosit dengan ukuran diameter kecil memiliki potensi untuk menjadi embrio dengan kualitas baik.

During oogenesis, oocytes grow in size and acquire maturation competence. Oocyte maturation competence is necessary to support fertilization and the development of good quality embryos. The inability to determine which oocytes have the potential to produce viable embryos remains a major obstacle in the In Vitro Fertilization (IVF). This study aims to determine whether oocyte diameter can be a predictor of oocyte and embryo quality. This study used a prospective cohort research design. The method used for measuring oocyte diameter using Image J application. Each oocyte and cumulus granulosa cells is grouped according to the size of oocyte diameter, oocyte are fertilized with ICSI/IMSI techniques and then followed by embryo development until day 5. ELISA examination is used to confirm oocyte quality by looking at p-Akt and Akt total protein levels in oocyte cumulus granulosa cells, while to confirm embryo quality by looking at the morphokinetic embryo, blastocyst achievement and frequency of cleavage abnormalities. The results showed no significant difference (P>0.05) in p-Akt and Akt total protein levels in cumulus granulosa cells between the three groups. In addition, morphokinetic observation of embryos showed no significant difference (P>0.05) except S2 parameter, as well as the achievement of blastocyst and the frequency of cleavage abnormalities except the reverse cleavage (RC) parameter. The conclusion obtained from this study is that the size of the oocyte diameter does not affect the quality of oocytes and embryos. Oocytes diameter size can not be a predictor of oocyte and embryo quality, because there is no significant difference in the quality of oocytes and embryos of the three groups. Oocytes with a small diameter size have the potential to become embryos with good quality."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
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UI - Tesis Membership  Universitas Indonesia Library
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Steven Arianto
"Mukopolisakaridosis tipe II (MPS II) merupakan penyakit kelainan lisosomal langka yang disebabkan oleh mutasi pada gen iduronat 2-sulfatase (IDS) dapat menyebabkan disfungsi dari enzim I2S yang dihasilkan sehingga molekul heparan sulfat (HS) dan dermatan sulfat (DS) terakumulasi pada jaringan. Penelitian ini dilakukan untuk mengetahui dan menganalisis hubungan kadar HS dan DS urin dengan jenis mutasi gen IDS pada penderita MPS II di Indonesia. Data susunan nukleotida gen IDS dari tujuh pasien MPS II dianalisis untuk melihat jenis mutasi dan dibuat model 3D proteinnya. Analisis 3D protein akan dikorelasikan dengan kadar HS dan DS urin pasien tersebut yang diukur menggunakan metode Enzyme-Linked Immunosorbent Assay (ELISA). Hasil analisis mutasi ditemukan beberapa jenis mutasi, seperti mutasi nonsense (1/7), delesi (2/7), insersi (1/7), dan missense (3/7). Dari ketujuh pasien tersebut, tiga diantaranya (P2, P6, P7) telah menjalani terapi ERT. Kadar HS urin dari ketujuh pasien menunjukkan peningkatan yang beragam dibandingkan dengan kadar HS normal. Berbeda dengan HS, kadar DS urin sampel pasien ada yang mengalami sedikit peningkatan (P1, P2, P7) dan ada pula yang tetap berada pada rentang kadar DS normal (P3, P4, P5, P6). Keragaman kadar HS dan DS sampel pasien tersebut sangat dipengaruhi oleh letak mutasi, jenis mutasi, diagnosis dan prognosis yang ditegakkan sedini mungkin, terapi ERT yang telah dilakukan pasie, durasi ERT, dan respon masing-masing pasien terhadap pengobatan yang telah diberikan.

Mucopolysaccharidosis type II (MPS II) is a rare lysosomal disorder caused by mutations in the iduronat 2-sulfatase (IDS) gene that can cause dysfunction of I2S enzyme so that the heparan sulfate (HS) and dermatan sulfate (DS) molecules accumulate in the tissue. This study was conducted to determine and analyze the relationship of urinary HS and DS levels with the type of IDS gene mutation in MPS II patients in Indonesia. The nucleotide of IDS genes sequences from seven MPS II patients were analyzed to see the type of mutation and the 3D protein model was made. 3D protein analysis will be correlated with urinary HS and DS levels of the patients measured by using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Results of mutation analysis results found several types of mutations, such as nonsense mutations (1/7), deletions (2/7), insertions (1/7), and missense (3/7). From the seven patients, three of them (P2, P6, P7) had undergone ERT therapy. The urine HS level of the seven patients showed a varied increase compared to normal HS levels. In contrast to HS, the urine DS level of the sample of patients had a slight increase (P1, P2, P7) and some remained in the normal DS level range (P3, P4, P5, P6). The diversity of HS and DS levels of the patient's samples is strongly influenced by the location of the mutation, type of mutation, diagnosis and prognosis that is enforced as early as possible, ERT therapy has been carried out, ERT duration, and each patient's response to the treatment given."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
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UI - Tesis Membership  Universitas Indonesia Library
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Ema Susiana
"ABSTRAK
LATAR BELAKANG: Proses remodelling tulang ditentukan oleh keseimbangan antara proses pembentukan oleh osteoblast dan resorpsi sel tulang oleh osteoklas. Osteprotegerin (OPG) memiliki peran penting dalam menghambat proses resorpsi tulang oleh osteoklas. Pada wanita menopause, proses resorpsi lebih tinggi daripada proses pembentukan tulang, sehingga dapat mengakibatkan terjadinya osteoporosis. Pada penelitian ini, single nucleotide polymorphisms (SNPs) pada daerah promoter gen OPG diteliti untuk mengetahui hubungannya dengan risiko osteoporosis pada wanita menopause.
BAHAN dan CARA KERJA: Penelitian ini melibatkan 285 wanita Indonesia menopause yang terdiri dari 81 wanita normal, 143 wanita dengan osteopenia dan 61 wanita dengan osteoporosis. Angka T-score diperoleh dengan pengukuran menggunakan Ultrasound Densitometry. Analisis genetik dilakukan menggunakan teknik PCR-RFLP. Analisis statistik menggunakan uji chi-square dengan asumsi kemaknaan p<0,05.
HASIL: Hasil penelitian memperlihatkan bahwa frekuensi genotip (TT, TC dan CC) pada semua kelompok (normal, osteopenia dan osteoporosis) tidak berbeda bermakna (p>0,05). Frekuensi alotip (alel T dan C) pada semua kelompok juga tidak berbeda bermakna (p>0,05). Hasil perhitungan odd ratio dengan menggunakan genotip TT sebagai pembanding memperlihatkan bahwa genotip CC memiliki kemungkinan mengalami gangguan kelainan tulang (osteopenia dan osteoporosis) 0,29 kali (22%) dan TC 0,88 kali (46%) lebih besar dibandingkan dengan genotip TT. Dari hasil penelitian ini, dapat disimpulkan bahwa SNP T950C tidak memiliki peranan dalam kejadian osteoporosis pada wanita menopause di Indonesia.

ABSTRACT
INTRODUCTION: Bone remodelling process is determined by the balance between the bone formation and resorption. Osteoprotegerin (OPG) has an important role to inhibit bone resorption by osteoclast. In menopausal women, the rate of bone resorption is higher than its formation, thereby inducing osteoporosis. In this study, single nucleotide polymorphism (SNPs) in promoter region of gene OPG is studied regarding to the association to the risk of the osteoporosis in menopausal Indonesian women.
MATERIAL and METHODS: The study samples consist of 285 menopausal Indonesian women, of which 81 are classified as normal (healthy), 143 are with osteopenia and 61 are with osteoporosis. T-score is obtained from the measurement using Ultrasound Densitometry, and genetic polymorphism analysis was performed by PCR RFLP. The statistical analysis uses chi-square with significance assumption at p<0.05.
RESULT: This study shows the frequency of genotypes (TT, TC and CC) to all groups (normal, osteopenia and osteoporosis), but it does not demonstrate any significant differences (p>0.05). The frequency of allotypes (T and C) to all groups also does not show the significance (p>0.05). Odd ratio calculations demonstrate that the possibility of developing bone disorders (osteopenia and osteoporosis) for both CC genotype and TC genotype is higher than TT genotype, as much as 0.29 times higher (22%) and 0.88 times higher (46%), respectively."
2013
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Sri Murni Asih
"Latar Belakang: Virus Epstein~Barr (EBV) merupakan virus dsDNA dan termasnk dalam famili Herpesviridae. Infeksi EBV dapat berasosiasi dengan beberapa penyakit seperti karsinoma nasofaring (KNF). Pada penderita KNF, gen EBV yang diekspresikan adalah gen lain, yaitu EBERs, EBNAI, LMP 1, LMPZA, dan LMPZB. Dari kesemua gen tersebuf., LMPI dianggap yang berperan penting dalam proses onkogenesis dan transformasi limfosit B oleh EBV. Dan beberapa Studi epidemiologi, ditemukan adanya Varian khusus pada gen LMP] berupa deiesi 30 pb pada bagian C-terminal. Di Indonesia, hingga saat ini belum diketahui apakah ditemukan delesi 30 pb gen LMPI pada penderita KNF dan bila ditemukan, apakah delesi tersebut berhubungan dengan patogenesis KNF.
Tujuan: Mengetahui apakah ditemukan delesi 30 pb gen LMP] EBV pada penderita KNF di Indonesia, dan bila ditemukan berapa frekuensi delesi 30 pb gen LMPI EBV pada penderita KNF di Indonesia, Serta mengetahui hubungan antara delesi tersebut dengan status patologi KNF.
Metode: Identifikasi delesi 30 pb gen LMPI Vi1'l.lS Epstein-Barr dilakukan dengan metode nested PCR dan hasil PCR divisualisasi dengan elektroforesis menggunakan gel agarose 2%. Hasil amplifikasi bempa pita DNA berukuran 162 pb untuk gen LMPI yang tidak mengalarni delesi 30 pb, sedangkan pita DNA berukuran 132 pb untuk gen LMP! yang mengalami delesi 30 pb.
Hasil: Dari 100 sampel penderita KNF yang diidentifikasi, 29 sampel mengalami delesi 30 pb, 71 sampel tidak mengalami delesi 30 pb, dan 21 sampel mengalami coexislence varian.
Kesimpulan: Di Jakarta, varian EBV berupa delesi 30 pb gen LMPI ditemukan dalam frekuensi yang rendah (24%; 29/ 121) bila dibandingkan varian yang tidak mengalami delesi 30 pb (76%; 92/121). Pada penelitian ini juga ditemukan adanya coexisrence Varian gen LMPL Berdasarkan uji Fisl1er's Exact, didapat bahwa nilai p > 0,05, berarti tidak ada hubungan bermakna antara delesi 30 pb gen LMPI dengan status patologi KINF.

Background: Epstein-Barr virus (EBV) is a dsDNA virus, member of Herpes (Herpesviridae) family. EBV infection may be associated with several diseases, one of them is nasopharyngeal carcinoma (NPC). NPC patients expressed EBV latent gene, they are EBERS, EBNA1, LMPI, LMPZA, and LMPZB. LMPI, in particular play important roles in epithelial oncogenesis and B lymphocyte transformation. Several epidemiological studies found specific variant of LMPI gene detectable as 30-bp deletion of C-tenninal region of LMP] gene. There is not any report of 30-bp LMP] gene on NPC patients so far and it is still unclear whether the deletion is associated with NPC pathogenesis.
Purpose: (1) To understand the existence of the deletion of 30-bp LMP1 gene in Indonesia NPC patients. (2) To determine the frequency of 30-bp deletion of LMP1 gene and its association with pathological status.
Method: Identification of 30-bp deletion in LMPI gene was done by nested PCR method. The PCR result was investigated by means of electrophoresis in 2% agarose gel. The results were determined as 162 bp of DNA band of LMPI gene (without 30-bp deletion) and 132 bp of DNA band of LMP1 gene (with 30-bp deletion).
Results: Among 100 identified samples, 29 samples found to have 30-bp deletion, 71 samples doesn?t have 30-bp deletion and 21 samples carry coexistence variants.
Conclusion: In Indonesia, especially in Jakarta, EBV variant of 30-bp deletion of LMP1 gene was found in low frequency (21-l»%; 29/ 121) in comparison with variant without deletion (76%; 92/121). There are variant of LMPI gene mixtures (coexistence with and without deletion). Analysis of data using Fisher°s Exact test (p>0,05) showed that there is not significant relationship between 30~bp deletion of LMPI gene and NPC pathological status.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2008
T32888
UI - Tesis Open  Universitas Indonesia Library
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Sri Wahyuni Dwintasari
"Latar Belakang: Metode PCR dapat digunakan untuk mengidentifikasi DNA suatu organisme. ldentifikasi gen 18S rRNA sudah hanyak dipakai untuk mempelajari sejumlah organisms eukariot seperti tanaman, hewan dan protozoa termasuk Cryptosporidium sp. Penelitian terdahulu pada anak batita di daerah kumuh dan rawan banjir di Jakarta yang dideteksi secara mikroskopis dengan pcwarnaan modifikasi tahan 838111 (MTA), didapatkan prevalensi 2,l% yang rendah dibandingkan negara berkembang lain yang keadaan lingkungan dan populasinya mirip Indonesia. Deteksi Cryptosporidium sp. secara molekular di feses dengan PCR memungkinkan diagnosis lebih akurat dan cepat.
Tujuan: mengembangkan metode PCR :mink deteksi gen ISS rRNA Cryptosporidium sp. pada feses yang disimpan dalam larutan kalium bikromat 2,5% selama 1 bulan.
Metode: sejumlah 188 sampel feses yang disimpan dalam larutan kalium bikromat dikonsentrasikan dengan teknik air-eter, selanjutnya dilakukan ekstraksi DNA terhadap konsentrat dan sebagian lagi dipulas dengan MTA. Amplifikasi DNA Cryptosporidium terhadap gen 18S rRNA dilakukan dengan program PCR iangsung, siklus 39 kali.
Hasil: pemeriksaan dengan metode MTA konsentrasi didapatkan sembilan sampel positif (4,8%) sedangkan dengan PCR didapatkan 65 sampel positif (34,6%).
Kesimpulan: Larutan kalium bikromat dapat dipakai untuk penyimpanan ookista Cryptosporidfwn sp. tanpa mempengaruhi hasil PCR maupun mikroskopis.

Background: PCR method can be used to characterize an organism DNA. Identification of 18S rRNA gene has been widely used to study eukaryotes like plants, animals and protozoa such as Cryptosporidium sp. Previous study on Cryptosporidium sp. in children under tluee years old in a slum area in Jakarta, detected by direct modiiied acid fast (MAF) showed 2.1% prevalence, which was unexpectedly much lower than other developing country with similar enviromnent and study population. Detection of Cryptosporidium sp. by molecular technique, PCR will offer more accurate and efficient diagnosis.
Objective: develop PCR method to detect Cryptosporidium sp. 18S rRNA gene of stool from stools preserved in potassium dichromate solution for 13 months.
Methods: There were l88 stool samples which have been kept in 2.5% potassium dichromate for 13 months. These samples were concentrated by water-ether technique, extracted the DNA and stained by MAF. Amplihcation of Cnprosporidium sp. ISS rRNA gene was using direct PCR for 39 cycles.
Result: of samples with MAF has found 9 positive (4,8%) and samples with PCR has presented 65 positive (34,6%).
Conclusion: Potassium dichromate solution can be used to preserve oocysts of Cryptosporidium sp since it does not interfere the PCR and microscopic examination result.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2008
T33065
UI - Tesis Open  Universitas Indonesia Library
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Syurri Innaddinna Sy
"Ameloblastoma merupakan tumor jinak yang berkembang lambat, bersifat invasif secara lokal dan sering terjadi rekurensi. Ameloblastoma tipe multikistik/padat merupakan tipe yang paling sering ditemukan. Cell adhesion molecules (CAMs) mempunyai peranan penting dalam proses morfogenesis jaringan pada saat perkembangan dan mempertahankan diferensiasi jaringan pada organisme dewasa. Faktor adhesi seluler dan motility merupakan mekanisme yang bertanggung jawab terhadap inisiasi dan perkembangan tumor. E-cadherin adalah molekul adhesi antar sel paling berpengaruh dalam adherens junction yang menjaga sel epitel melekat satu sama lain. Hilangnya fungsi protein E-cadherin sebagai tumor suppresor berhubungan dengan meningkatnya sifat invasif dan metastasis tumor.
Tujuan penelitian ini adalah untuk menganalisis ekspresi Ecadherin pada ameloblastoma multikistik/padat pola folikuler, pola pleksiformis, dan pola campuran.
Metode penelitian : 52 kasus ameloblastoma multikistik/padat dilakukan pemeriksaan ekspresi E-cadherin secara imunohistokimia. Hasil penelitian dievaluasi secara semikuantitatif, dengan melihat persentase sel tumor yang terpulas dan intensitas pulasan.
Hasil : sampel penelitian berjumlah 52 (18 pola folikuler, 14 pola pleksiformis, dan 20 pola campuran). Secara imunohistokimia E-cadherin terekspresi pada lebih dari 50% sel tumor. Analisis secara statistik menunjukkan tidak terdapat perbedaan yang bermakna antara ketiga pola ameloblastoma multikistik/padat (p>0,05).
Kesimpulan : pada hasil penelitian tampak bahwa ekspresi E-cadherin antara ketiga pola ameloblastoma multikistik/padat tidak menunjukkan perbedaan bermakna.

Ameloblastoma is a benign tumor that slow-growth, locally invasive and high rate of recurrence. Ameloblastoma multicystic/solid is the most commonly found. Cell adhesion molecules (CAMs) have an important role, in the process of tissue morphogenesis during development and maintaining tissue differentiation in the adult organism. Cellular adhesion and motility factor is the mechanism responsible for tumor initiation and progression. E-cadherin is the most important cell adhesion molecules in the adherens junctions that maintain epithelial cells attached to one another. Loss of function of E-cadherin as tumor suppresor protein associated with increased invasive and metastatic behavior of tumor.
The purpose of this study was to analyze the expression of E-cadherin of multicystic/solid ameloblastoma in the follicular pattern, plexiform pattern, and mixed pattern.
Method : E-cadherin expression of 52 cases of multicystic/solid ameloblastoma investigated by immunohistochemical. The results were evaluated semiquantitatively, by investigating the percentage immunopositive of tumor cells and intensity of staining.
Results: 52 sample (18 follicular pattern, 14 plexiform pattern and 20 mixed pattern). E-cadherin expressed on more than 50% of tumor cells. Statistical analysis showed no significant difference among the three patterns ameloblastoma multicystic (p>0,05).
Conclusion: The expression of Ecadherin among the three patterns ameloblastoma multicystic/solid showed no significant difference.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2013
T59126
UI - Tesis Membership  Universitas Indonesia Library
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Yuliandini Pangestika
"Latar belakang: Mukopolisakaridosis (MPS) tipe II adalah kelainan genetik yang ditandai dengan gangguan metabolik berupa defisiensi enzim iduronat-2-sulfatase (I2S) karena adanya mutasi pada gen iduronat-2-sulfatase (IDS), sehingga heparan sulfat dan dermatan sulfat tidak terdegradasi dan terakumulasi pada jaringan. Penelitian ini dilakukan untuk menganalisis aktivitas spesifik enzim I2S dan kaitannya dengan varian mutasi gen IDS pada pasien MPS II di Indonesia.
Metode: Data sekuen nukleotida gen IDS dari enam pasien MPS II dianalisis untuk melihat jenis mutasi serta dibuat model konformasi proteinnya. Sel peripheral blood mononuclear cell (PBMC) diisolasi menggunakan metode sentrifugasi bertingkat dan dikultur menggunakan medium RPMI. Nilai aktivitas spesifik I2S diperoleh dengan mengukur aktivitas I2S per miligram konsentrasi total protein. Aktivitas enzim I2S diukur menggunakan metode fluorometri, sementara konsentrasi total protein diukur menggunakan bicinchoninic acid (BCA) protein assay. 
Hasil: Tiga varian mutasi yang ditemukan pada pasien MPS tipe II adalah missense (3/6), delesi (2/6), dan nonsense (1/6). Aktivitas enzim spesifik I2S pada pasien menunjukkan angka yang bervariasi. Mutasi dengan rata-rata aktivitas spesifik I2S paling rendah sampai paling tinggi secara berurutan adalah mutasi delesi (0,026 nmol/min/mg), missense (0,052 nmol/min/mg), dan nonsense (0,052 nmol/min/mg). 
Kesimpulan: Aktivitas spesifik enzim I2S pada pasien MPS tipe II di Indonesia 0,044 nmol/min/mg, sedangkan pada kontrol adalah 0,172 nmol/min/mg. Nilai rata-rata aktivitas spesifik I2S pada pasien menurun empat kali lipat dibandingkan pada kontrol.

Background: Mucopolysaccharidosis type II (MPS II) is an inherited metabolic disorder that caused by iduronate-2-sulfatase (I2S) enzyme deficiency due to mutations in the iduronate-2-sulfatase (IDS) gene, so that heparan sulfate and dermatan sulfate do not be degrade and accumulate in tissues. This study was conducted to analyze the specific activity of I2S and its relationship to IDS variant mutation of MPS II patients in Indonesia.
Method: IDS gene nucleotide sequences from six MPS II patients were analyzed to see mutation type and protein conformation model was made. Peripheral blood mononuclear cell (PBMC) were isolated using a stratified centrifugation and cultured using the RPMI medium. I2S specific activity values are obtained by measuring I2S activity per milligram of total protein concentration. I2S enzyme activity was measured using fluorometry method, while total protein concentration was measured using bicinchoninic acid (BCA) protein assay.
Result: There were three variant mutation in MPS II patients, such as missense (3/6), deletion (2/6), and nonsense (1/6). I2S specific enzyme activity shows varying numbers. IDS mutation based on I2S specific activity from lowest to highest mean value are deletion (0.026 nmol/min/mg), missense (0.052 nmol/min/mg), and nonsense (0.052 nmol/min/mg).
Conclusion: I2S specific activity in MPS II patient is 0,044 nmol/min/mg, while the control is 0,172 nmol/min/mg based on the mean value. I2S specific activity in patients decreased four times compared to controls.
"
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2020
T-Pdf
UI - Tesis Membership  Universitas Indonesia Library
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Supraja Dwiyono
"[ABSTRAK
Doksorubisin merupakan salah satu antikanker golongan antrasiklin yang efektif,
untuk keganasan di darah. Akan tetapi, seperti antikanker konvensional pada
umumnya, penggunaan doksorubisin dapat menyebabkan berbagai efek samping pada
organ lain, misalnya pada testis sehingga penggunaannya di klinis menjadi terbatas.
Hal ini disebabkan karena mekanisme antikanker doksorubisin dapat juga
menimbulkan toksisitas pada testis. Peningkatan stress oksidatif adalah salah satu
mekanisme dapat menyebabkan kerusakan pada organ tersebut. Mangiferin sebagai
zat antioksidan alami, terkandung dalam Mangifera Indica L. diperkirakan dapat
digunakan untuk mengurangi toksisitas testis. Namun sampai saat ini, belum ada
penelitian yang mengeksplor efek proteksi mangiferin terhadap kerusakan oksidatif
testis yang diinduksi doksorubisin.
Penelitian ini menggunakan tikus jantan Sprague Dawley, yang dibagi menjadi empat
kelompok. Masing-masing kelompok terdiri dari enam ekor tikus. Tikus pada
kelompok kontrol negatif diberikan doksorubisin secara intraperitoneal (dosis total 15
mg/kgBB) dan kelompok normal diberikan NaCl 0,9%. Mangiferin (dosis 30 dan 60
mg/kg BB) diberikan oral selama tujuh minggu. Setelah, tujuh minggu tikus
dimatikan dan testis dikumpulkan untuk analisis parameter stress oksidatif biokimia
kadar MDA (malonedyaldehide), aktivitas SOD (Superoxide Dysmutase), perubahan
histologi dan apoptosis kaspase-9 dan kaspase-12. Hasil penelitian menunjukkan
bahwa pemberian doksorubisin selama dua minggu dapat meningkatkan kadar MDA,
menyebabkan kerusakan sel spermatogenik, sel Sertoli dan penciutan diameter
tubulus seminiferus testis, peningkatan ekspresi kaspase-9 di sisi luminal yang
diberikan doksorubisin. Pemberian mangiferin dosis 30 dan 60 mg/kg BB selama
tujuh minggu dapat mengurangi kerusakan sel spermatogenik dan sel Sertoli tubulus
seminiferus testis, penurunan kadar MDA dan penurunan ekspresi kaspase-9 pada
kelompok perlakuan diberikan doksorubisin dan mangiferin. Perbaikan parameterparameter
ini mengindikasikan bahwa mangiferin mempunyai efek proteksi terhadap
kerusakan sel spematogenik dan sel sertoli tubulus seminiferus testis tikus yang
diberikan doksorubisin.

ABSTRACT
Doxorubicin, one of the anthracycline anticancer class, is effective especially in blood
malignancy. However, as in the general use of the conventional anticancer-drugs.
Doxorubicin can cause various side effects in other organs, such as the testes so that
its use in clinical become limited. This is because of the anticancer mechanism can
cause cytotoxicity on testes. The increased oxidative stress is the main mechanism
that can be the causal. Mangiferin as a natural antioxidant substance, contained in
Mangifera Indica L., is expected to reduce the toxicity. The Antioxidants are
expected to reduce the toxicity of the testes. But until now, no studies have explored
the effects of mangiferin protection against oxidative damage induced testicular
doxorubicin.
This study used male Sprague Dawley rats, which were divided into four groups.
Each group consisted of six mice. Rats in the negative control group was given
intraperitoneal doxorubicin (total dose 15 mg/kg) and the normal group was given
normal saline 0.9%. Mangiferin (doses of 30 and 60 mg/kg) was administered orally
for seven weeks to the treatment gtoups (both DOX and MAG were given). After
seven weeks-off, testes of mice were collected for analysis of biochemical parameters
i.e. oxidative stress levels of MDA and SOD activity, histology and apoptosis of the
caspase-9 and of the caspase-12. The results showed that administration of
doxorubicin for two-weeks can cause damage to Sertoli, spermatogenic cells and
shrinking of diameter of testicular seminiferous tubules, increasing the levels of
MDA, increasing in the expression of caspase-9 on the luminal side in the treatment
group was given doxorubicin. This possibility of the doxorubicin dose given is too
toxic to the testes in this study. Mangiferin dose administration of 30 and 60 mg / kg
for seven-weeks can reduce the damage of Sertoli and spermatogenic cells of the
testicular seminiferous tubules, decrease levels of MDA, reduce Sertoli,
spermatogenic cell and diameter of the testicular seminiferous tubulus damage,
decrease caspase-9 expression only on luminal side of the seminiferus tubulus in the
groups given both of doxorubicin and mangiferin. these parameters indicate that
mangiferin, which has antioxidant?s activity, provides protective effects against
oxidative damage in spematogenic and Sertoli cell testicular seminiferous tubules of
mice given doxorubicin, Doxorubicin, one of the anthracycline anticancer class, is effective especially in blood
malignancy. However, as in the general use of the conventional anticancer-drugs.
Doxorubicin can cause various side effects in other organs, such as the testes so that
its use in clinical become limited. This is because of the anticancer mechanism can
cause cytotoxicity on testes. The increased oxidative stress is the main mechanism
that can be the causal. Mangiferin as a natural antioxidant substance, contained in
Mangifera Indica L., is expected to reduce the toxicity. The Antioxidants are
expected to reduce the toxicity of the testes. But until now, no studies have explored
the effects of mangiferin protection against oxidative damage induced testicular
doxorubicin.
This study used male Sprague Dawley rats, which were divided into four groups.
Each group consisted of six mice. Rats in the negative control group was given
intraperitoneal doxorubicin (total dose 15 mg/kg) and the normal group was given
normal saline 0.9%. Mangiferin (doses of 30 and 60 mg/kg) was administered orally
for seven weeks to the treatment gtoups (both DOX and MAG were given). After
seven weeks-off, testes of mice were collected for analysis of biochemical parameters
i.e. oxidative stress levels of MDA and SOD activity, histology and apoptosis of the
caspase-9 and of the caspase-12. The results showed that administration of
doxorubicin for two-weeks can cause damage to Sertoli, spermatogenic cells and
shrinking of diameter of testicular seminiferous tubules, increasing the levels of
MDA, increasing in the expression of caspase-9 on the luminal side in the treatment
group was given doxorubicin. This possibility of the doxorubicin dose given is too
toxic to the testes in this study. Mangiferin dose administration of 30 and 60 mg / kg
for seven-weeks can reduce the damage of Sertoli and spermatogenic cells of the
testicular seminiferous tubules, decrease levels of MDA, reduce Sertoli,
spermatogenic cell and diameter of the testicular seminiferous tubulus damage,
decrease caspase-9 expression only on luminal side of the seminiferus tubulus in the
groups given both of doxorubicin and mangiferin. these parameters indicate that
mangiferin, which has antioxidant’s activity, provides protective effects against
oxidative damage in spematogenic and Sertoli cell testicular seminiferous tubules of
mice given doxorubicin]"
2015
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Silvani Permatasari
"[ABSTRAK
Latar belakang: Proses pematangan sperma terjadi melalui interaksi spermatozoa dengan protein yang disekresikan ke lumen oleh sel epitel epididimis. Sekresi protein pada epididimis ditentukan oleh gen-gen yang terekspresi spesifik di epididimis. Ekspresi gen di epididimis dapat dipengaruhi oleh androgen atau faktor testikular. CD52 telah diketahui terekspresi di epididimis, namun regulasi yang mempengaruhi ekspresi gen CD52 di epididimis belum diketahui. Tujuan dari penelitian ini adalah untuk menganalisis ekspresi dan regulasi gen CD52 agar dapat memprediksi perannya di epididimis mencit. Metode: Analisis bioinformatika dilakukan untuk memprediksi sinyal peptida dan domain fungsional dari CD52. Quantitative real time RT-PCR digunakan untuk mengukur ekspresi relatif gen CD52 pada analisis spesifisitas jaringan, ketergantungan terhadap androgen dan faktor testikular, serta postnatal development. Hasil: CD52 memiliki sinyal peptida yang menunjukkan ciri protein sekretori dan terekspresi secara spesifik di epididimis. Ekspresi CD52 yang tertinggi terdapat di bagian cauda. Ekspresi CD52 pada mencit diregulasi oleh androgen yang ditandai dengan penurunan pada hari pertama dan ketiga setelah digonadektomi dan pemberian testosteron eksogen setelah gonadektomi dapat menjaga ekspresi CD52 50% dari kadar normalnya. Eksperimen dengan memberikan reseptor androgen antagonis (flutamide) juga mendukung bahwa ekspresi CD52 sangat tergantung terhadap androgen. Ekspresi CD52 menurun sangat bermakna hingga mencapai 93% dibandingkan dengan kontrol. Selain androgen, ekspresi CD52 juga dipengaruhi oleh faktor testikular. Ekspresi CD52 mengalami penurunan bermakna dari hari pertama hingga kelima setelah perlakuan efferent duct ligation (EDL) hingga mencapai 75% dari kontrol. Selain itu ekspresi CD52 juga dipengaruhi oleh perkembangan pasca lahir. Ekspresi CD52 meningkat di hari ke-15 hingga hari ke-60 pasca lahir. Kesimpulan: CD52 merupakan gen penyandi protein sekretori yang terekspresi spesifik di epididimis pada region cauda dan regulasinya dipengaruhi oleh androgen, faktor testikular, dan perkembangan pasca lahir.

ABSTRACT
Background. Epididymal sperm maturation is occurs via interactions between sperm and proteins secreted by epididymal epithelium. These proteins are encoded by genes that are specifically expressed in a region-specific manner. Previous studies have demonstrated that epididymal genes are regulated by androgen and testicular factors. CD52 is an epididymal gene putatively involved in sperm maturation. However, the regulation of its expression in the epididymis has not been fully understood and little is known about its role during sperm maturation process. Therefore, this study was aimed to analyze the expression and regulation of CD52 in the mouse epididymis. Method. Bioinfomatic analyses were perfomed to predict signal peptides and functional domains of CD52. Quantitative real-time RT-PCR was used to analyze tissue distribution, androgen, testicular factors dependency and postnatal development. Results. CD52 amino acid sequence contains a signal peptide, indicating it is a secretory protein. CD52 exhibited region-spesific expression in the epididymis with the highest level was in cauda. Mice CD52 expression was regulated by androgen indicated by a decrease started at day 1 following a gonadectomy. Interestingly, testosterone replacement therapy was able to maintain the expression at 50% of normal level. Experiment by given androgen receptor antagonist, flutamide showed decrease of CD52 expression about 93% than control. It?s confirming that CD52 expression depend on androgen. Moreover, testicular factors also influenced CD52 expression. This was revealed by efferent duct ligation in which CD52 expression was reduced at day 1 to day 5 following the ligation. Finally, CD52 expression was developmentally regulated, this was indicated by increase in the level of expression start at day 15 postnatally. Conclusion: CD52 is a secretory protein and exhibited region-spesific expression in the cauda epididymis. It is regulated by androgen, testicular factors, and also affected by development stage.
, Background. Epididymal sperm maturation is occurs via interactions between sperm and proteins secreted by epididymal epithelium. These proteins are encoded by genes that are specifically expressed in a region-specific manner. Previous studies have demonstrated that epididymal genes are regulated by androgen and testicular factors. CD52 is an epididymal gene putatively involved in sperm maturation. However, the regulation of its expression in the epididymis has not been fully understood and little is known about its role during sperm maturation process. Therefore, this study was aimed to analyze the expression and regulation of CD52 in the mouse epididymis. Method. Bioinfomatic analyses were perfomed to predict signal peptides and functional domains of CD52. Quantitative real-time RT-PCR was used to analyze tissue distribution, androgen, testicular factors dependency and postnatal development. Results. CD52 amino acid sequence contains a signal peptide, indicating it is a secretory protein. CD52 exhibited region-spesific expression in the epididymis with the highest level was in cauda. Mice CD52 expression was regulated by androgen indicated by a decrease started at day 1 following a gonadectomy. Interestingly, testosterone replacement therapy was able to maintain the expression at 50% of normal level. Experiment by given androgen receptor antagonist, flutamide showed decrease of CD52 expression about 93% than control. It’s confirming that CD52 expression depend on androgen. Moreover, testicular factors also influenced CD52 expression. This was revealed by efferent duct ligation in which CD52 expression was reduced at day 1 to day 5 following the ligation. Finally, CD52 expression was developmentally regulated, this was indicated by increase in the level of expression start at day 15 postnatally. Conclusion: CD52 is a secretory protein and exhibited region-spesific expression in the cauda epididymis. It is regulated by androgen, testicular factors, and also affected by development stage.
]"
2015
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Trisia Lusiana Amir
"ABSTRAK
LATAR BELAKANG: Tatalaksana penyakit Graves (GD) lebih umum dilakukan dengan obat antitiroid, namun lebih dari 50% penderita GD dapat kambuh setelah kondisi remisi. Hal ini dapat dipengaruhi oleh faktor genetik dan lingkungan. Salah satu gen yang meregulasi respon imun GD adalah gen CD40 yang secara umum diekspresikan pada permukaan limfosit B. Penelitian ini bertujuan untuk mengetahui variasi genetik gen CD40 daerah 5?-UTR dan pengaruhnya terhadap kadar sCD40 dalam serum, serta peran faktor klinis dalam memengaruhi kekambuhan pada penderita GD.
METODE: Penelitian ini merupakan studi kasus kontrol yang membandingkan 30 penderita GD yang kambuh dan 30 penderita GD yang tidak kambuh setelah obat antitiroid dihentikan. Analisis variasi genetik dilakukan dengan metode PCRRFLP dan pengukuran kadar sCD40 dalam serum dengan metode ELISA. Analisis statistik yang dilakukan adalah uji chi-square, uji t tidak berpasangan dan uji Mann Whitney, dengan kemaknaan p<0,05.
HASIL: Variasi genotip dan alotip gen CD40 C/T-1 daerah 5?-UTR serta jenis kelamin tidak menunjukkan hubungan yang bermakna terhadap risiko kekambuhan GD (p>0,05), namun penelitian ini berhasil membuktikan adanya hubungan yang signifikan antara kadar sCD40 dalam serum (p<0,001) dan usia saat diagnosis (p=0,001) dengan risiko kekambuhan pada penderita GD. Hubungan antara variasi genotip gen CD40 dengan kadar sCD40 tidak menunjukkan perbedaan yang bermakna (p>0,05), namun genotip CC dan CT memiliki rerata kadar sCD40 yang lebih tinggi daripada genotip TT.
KESIMPULAN: Variasi genetik gen CD40 C/T-1 daerah 5?-UTR tidak berperan dalam peningkatan kadar sCD40 dan risiko kekambuhan GD, namun kadar sCD40 dan usia diagnosis berperan pada kekambuhan GD.

ABSTRACT
Background: The most common of Graves? Disease (GD) treatment is antithyroid drug but more than 50% patients can relapse after remission period. This can be influenced by genetic and environment factors. One of the genes that have regulation on immune response is CD40 gene in the surface of Lymphocyte B. The aim of this research to determine genetic variation in 5?-UTR CD40 gene, association to sCD40 level in serum, and the role of clinical factors that influence the risk for relapse in GD patients.
Methods: This research is a case-control study comparing 30 relapse patients and 30 non-relapse patients after treatment with anti-thyroid drug was terminated. Genetic variation was analyzed with PCR-RFLP. Measurement of sCD40 level in the serum had been analyzed by ELISA method. Statistical analyses were chisquare, independent t-test, Mann-Whitney test, a two-tailed p value less than 0.05 was considered significant.
Results: Genotype and alleles 5?-UTR CD40 gene variation as well as sex shown no association with risk for relapse (p>0.05), but sCD40 level in serum and age of diagnosis were considered significant with risk for relapse (p=0.001). Association between genotype variation in CD40 gene and sCD40 level were not significant (p>0.05) but sCD40 level in genotype CC and CT were higher than TT.
Conclusions: Genetic variation in 5?-UTR CD40 gene has no role to increase sCD40 level and risk for relapse but sCD40 level in serum and age of diagnosis have a role for relapse in GD patients.
"
Depok: Fakultas Kedokteran Universitas Indonesia, 2015
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