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Zen Hafy
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2008
D1768
UI - Disertasi Open  Universitas Indonesia Library
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Luthfiralda Sjahfirdi
"Javan gibbon (Hylobates moloch AUDEBERT 1797) is one of at least thirteen species of gibbons, which make up the Family Hylobatidae (Groves 2001: 289). The Javan gibbon is endemic to Java, Indonesia and now found only in fragmented forest tracts in the western and central portions of the island. As such, the conservation of this species has 'become a high priority for the government of Indonesia and the World. Habitat loss combined with illegal hunting and live capture has reduced the-Javan gibbon numbers in the wild to under 5000 individuals. Javan gibbon populations in zoos worldwide number less than 10 successful breeding pairs and live births have been extremely rare. The reasons for the low breeding success among captive Javan gibbons is not well understood but are likely to stem from a very limited knowledge of the basic reproductive biology/behavior. Expansion of genetic diversity and animal numbers in demographically isolated captive and wild populations are urgently required. Therefore, studies addressing female reproductive biology, particularly in providing data on the ovarian hormone profiles during ovarian cycle so to determine optimal mating time for assisted breeding, are a high priority.
This study aims to provide a detailed knowledge of basic reproductive biology in female Javan gibbons in captivity which is vital to promote population growth in captivity. This study was carried out to : (1) deine the endocrinology of the ovarian cycle in Javan gibbon by direct measurement of estradiol and progesterone in serum samples, (2) use serum hormones profiles to detennine the ovarian cycle and to predict the fertile phase of the cycle or Optimal Mating Time (GMT), (3) characterize the changes in vaginal epithelium and genital swelling, (4) evaluate cytological changes as Maturation Index (Ml), (5) correspond the similarity pattern of MI and genital swelling during ovarian cycle related to ovarian hormone profiles, and (6) monitor the time allocated to primary daily activity by captive-housed female Javan gibbons (Hylobales moloch) during their sexual cycle that live in pair to distinguish estrous period fiom anestrous one. This study was carried out from June 2003 to December 2003 for daily activity observations at Schmutzer Primate Center, Ragunan Zoo, Jakarta and Taman Sari Zoo, Bandung, and from September 2004 to April 2005 for blood sampling at Ragunan Zoo, Jakarta and Taman Sari Zoo, Bandung.
This is an exploration research that was conducted by daily observation and followed by blood sampling. Cycle status of all females was assessed daily by rating genital swelling following Czekala & Sicotte (2000: 210). Visual inspections of each gibbon sexual skin were observed daily for sign of swelling at 10 to 20 cm distance, while the animals are in caged as suggested by Heistermann et al. (1996: 845). The degree of wrinkling and the size of the labia minora will represent the primary physical features for evaluating changes in sex skin swelling during) the menstrual cycle. Four grades of were scored: 1 - no swelling; 2 - slightly swollen; 3 - nearly full swelling; 4 - fully swollen with additional coloration; Observations and sampling were conducted 2-month period that covered one complete ovarian cycle. Blood samples and vaginal swabs were taken at intervals of 3 to 4 days for the 2-month period. All sampling were conducted while the animal was under kethamine sedation; approximately 3 ml of blood was drawn from the femoral vein per sample. Blood collection was conducted by an experienced veterinarian or veterinarian technician on staff at the respective zoo in accordance with approved animal care and use protocols. Serum was drawn oif and stored in sealed vials at -20°C prior to EIA analysis to measure estrogen and progesterone levels during the ovarian cycle.
Daily observation was conducted to see how the limited area will influences their behavior including their reproductive behavior related to their hormonal regulation. Daily observations were divided into 2 (two) conditions, i.e. daily activity during esuus and during anestrus phase of the cycle. The vaginal morphology scores used to define estrus and anestrus phase. Estrous females were judged when the swelling scores were more than 1. The daily activities of 2 (two) female gibbons which were paired in each captivity were recorded base on ad-libitum method (Altmann 1974: 235). Observations were made by one observer, on an average of 5 to 6 days per week from 09:00 a.m. to 03:00 p.m. The Scan Sampling Method with five minutes duration for each sample point was used (Altmann 1974: 259), during visiting hours at both captivities. To measure the activity budgets, Dunbar (1988) methods was used. Activities of the animals were recorded, namely resting, moving, feeding, and grooming (in Matsumoto-Oda &. Oda 1998: 160), plus calling activity was added to be recorded, since gibbon?s calling is significantly spent during activity.
Results of this study were concluded as follows: The secretion patterns of estradiol and progesterone in serum Samples gave a reliable reflection of ovarian activity in captive-housed Javan gibbon. The range concentrations in cycling females of estradiol were 47.64 to 104.35 pg/ml and of progesterone were 0.5 to 10 ng/ml. The length of ovarian cycles was found to be 29 and 38 days, with follicular phase ranged from I9 to 24 days and luteal phase ranged from 7 to I2 days. The Optimal Mating Time was lasted 3 days after the day of estradiol surge or first day that progesterone levels begin to rise. From this study, two cycling females (0wa 1 and Owa 2) from Ragunan Zoo, displayed the lengths of the ovarian cycle ranging between 29 to 38 days. Two other females which live with their partners (Ulah at Schmutzer and Donna at Taman Sari Zoo) also displayed the length of the ovarian cycle by genital swelling observation. Their ovarian cycle length ranged between 29 to 30 days (for Ulah) and 26 to 36 days (for Donna). Despite the small sample and variability among animals, the limited subject animals using in this study gave an average ovarian cycle length of 315: 4.23 days, almost similar with other higher primates and human.
This study also found that genital swelling indicated correlationwith fluctuated estradiol values and could be useful as external marker to predict fertile phase of the cycle. The pattems of vaginal cytology were not consistent in all subjects during sampling period, theneafterthe patterns of comilication did not reliably reflect the physiological status ofthe animal, in contrast to many other species. Superficial cells presented throughout the cycle during sampling period corresponded with estrogen levels which never reach basal values.
Cycling female gibbons that live with their partners, demonstrated that in eslxous period, female tended to spend more time on calling, moving, and grooming. The dominant time spent on daily activity was for moving, that include brachiating leading to accommodate consortship behavior. Time spent for moving shown significantly different between estrus and anestrus, while feeding was less significant because of the availability of the food in captivity. They were more active in estrous than in anesmous condition."
Depok: Universitas Indonesia, 2006
D1229
UI - Disertasi Membership  Universitas Indonesia Library
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Sorontou, Yohanna
"Protein EBA-175 (Erythrocyte binding antigen-175) plasmodium falciparum merupakan ligan yang memperantarai perlekatan merozoit pada residu asam sialat glikoforin A pada eritrosit manusia dan oleh karena itu memegang peranan yang sangat penting pada invasi sel. Gen penyandi protein ini, eba-175 telah dibuktikan memiliki alel dimorfik, FCR (F) dan CAMP (C) yang dilaporkan berkaitan dengan manifestasi klinis malaria. Alel ini ditandai oleh adanya insersi nuleotida sebesar 423 pb pada alel F dan 342 pb pada alel C.
Suatu penelitian epidemiologi molekul yang bertujuan untuk menentukan frekuensi distribusi kedua alel tersebut serta kaitannya dengan manifestasi klinis malaria telah dilaksanakan pada isolat-isolat P. falciparum yang dikumpulkan dari pasien-pasien malaria asimptomatik dan simptomatik di Kabupaten Jayapura. Provinsi Papua melalui survei malariometrik dan pengumpulan sampel di pusat-pusat pelayanan kesehatan.
Analisis dengan teknik penggadaan DNA (Polymerase chain reaction) 110 isolat dari pasien asimptomatik dan 100 isolat dari pasien simptomatik menunjukkan bahwa alel C merupakan alel yang dominan pada kedua kelompok tersebut, dengan frekuensi distribusi pada malaria asimp-tomatik; alel C: 62.7%, alel C/F: 8%. Uji statistik dengan Chi-square menunjukkan tidak adanya keterkaitan antara alel-alel tersebut di atas dengan manifestasi klinis malaria.
Pengobatan kasus malaria dengan obat antimalaria sulfadoksin-pirimetamin (SP) menunjukkan adanya perubahan yang bermakna pada distribusi kedua alel tersebut dan dimana alel C ditemukan berkaitan dengan kegagalan pengobatan SP. Hasil-hasil yang diperoleh berbeda secara bermakna dengan frekuensi distribusi alel gen eba-175 yang dilaporkan di beberapa negara endemis malaria dimana alel F merupakan alel dominan. Dominasi alel C di Papua kemungkinan sebagian dapat dikaitkan dengan resistensi relatif alel tersebut terhadap obat SP."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2006
D624
UI - Disertasi Membership  Universitas Indonesia Library
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Lubis, Rosmawaty
"ABSTRAK
Resistensi terhadap lamivudin merupakan masalah yang sering dihadapi pada pengobatan penderita hepatitis B. Resistensi lamivudin biasanya dihubungkan dengan faktor virus yaitu mutasi gen P terutama di daerah YMDD, sedangkan penelitian pada faktor pejamu (host) belum pernah dilakukan. Penelitian ini bertujuan : 1) Untuk mengetahui peranan gen dCK pejamu (host) yang mengkode enzim deoksisitidin kinase pada resistensi lamivudin 2) Untuk mengetahui peranan gen P virus hepatitis B yang mengkode polimerase/reverse transcriptase pada resistensi lamivudin. Penelitian ini menggunakan metode Polymerase Chain Reaction (PCR) dan direct sequencing. Hasil penelitian menunjukkan bahwa gen dCK (ekson 2) relatif conserved. Mutasi yang tidak signifikan (G33W) ditemukan hanya pada satu pasien yang sensitif terhadap lamivudin, sedangkan pada kelompok pasien yang resisten terhadap lamivudin dan kelompok populasi nonnal tidak ditemukan mutasi. Penelitian pada gen P (domain RT) virus hepatitis B menemukan 1 (6,25 %) mutasi pada domain B yaitu L526M (rt LISOM) dan 6 (37,5%) mutasi pada domain C yaitu mutan YMDD yang terdiri atas 5 (3l,25%) mutan M5501 (rt M2040 dan 1 (6,25%) mutan M550V (rt M20-4V). Satu mutan MSSOV juga mengalami mutasi L526M. Pada penelitian ini juga ditemukan mutasi baru pada domain A yang belum pemah dipublikasikan yaitu Y487F (rt YI4IF), D480N (rt Dl34N) dan N485S (rt Nl39S). Mutan Y487F ditemukan pada 5 pasien (3l,25%) yang sama persis dengan mutasi MSSOI. Domain A dan C mempunyai peranan pada binding nukleosida trifosfal, sehingga diperkirakan mutasi baru yang ditemukan pada domain A juga mempunyai kontribusi terhadap terjadinya resistensi lamivudin. Virus yang mengalami mutasi L526M + MSSZV tidak menunjukkan mutasi pada Y487F, tetapi mengalami mutasi pada D48ON dan N485S. Kesimpulan yang dapat diambil dari penelitian ini adalah : 1) Pada level genetik tidak terjadi perubahan atau mutasi gen dCK (ekson 2) yang berhubungan dengan resistensi lamivudin. 2) Pada gen P (domain RT) virus hepatitis B terdapat mutasi pada domain A, B dan C yang berhubungan dengan resistensi terhadap lamivudin.

Abstract
The resistance against lamivudine treatment in hepatitis B patients is a problem frequently encountered by physicians. Lamivudine resistance is usually associated with viral mutations especially in the YMDD region of P gene, the involvement of host factors however, was not studied yet so far. This investigation is designed to determine either host or viral factors responsible responsible for lamivudine resistance. The aim of this study are : 1) To understand the involvement of host dCK gene which code for deoxycytidine kinase in lamivudine resistance. 2) To understand the involvement of viral P gene which code for polymerase/reverse transcriptase in lamivudine resistance. The investigation was performed by means of Polymerase Chain Reaction (PCR) and direct sequencing methods. The results indicate that dCK gene (exon 2) is relatively conserved. Unsignificant mutation (G33W) was found in only one patient who was sensitive to lamivudine treatment.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2005
D751
UI - Disertasi Membership  Universitas Indonesia Library
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Lubis, Rosmawaty
"ABSTRAK
Resistensi terhadap lamivudin merupakan masalah yang sering dihadapi pada pengobatan penderita hepatitis B. Resistensi lamivudin biasanya dihubungkan dengan faktor virus yaitu mutasi gen P terutama di daerah YMDD, sedangkan penelitian pada faktor pejamu (host) belum pernah dilakukan. Penelitian ini bertujuan : 1) Untuk mengetahui peranan gen dCK pejamu (host) yang mengkode enzim deoksisitidin kinase pada resistensi lamivudin 2) Untuk mengetahui peranan gen P virus hepatitis B yang mengkode polimerase/reverse transcriptase pada resistensi lamivudin. Penelitian ini menggunakan metode Polymerase Chain Reaction (PCR) dan direct sequencing.
Hasil penelitian menunjukkan bahwa gen dCK (ekson 2) relatif conserved. Mutasi yang tidak signifikan (G33W) ditemukan hanya pada satu pasien yang sensitif terhadap lamivudin, sedangkan pada kelompok pasien yang resisten terhadap lamivudin dan kelompok populasi nonnal tidak ditemukan mutasi. Penelitian pada gen P (domain RT) virus hepatitis B menemukan 1 (6,25 %) mutasi pada domain B yaitu L526M (rt LISOM) dan 6 (37,5%) mutasi pada domain C yaitu mutan YMDD yang terdiri atas 5 (3l,25%) mutan M5501 (rt M2040 dan 1 (6,25%) mutan M550V (rt M20-4V). Satu mutan MSSOV juga mengalami mutasi L526M. Pada penelitian ini juga ditemukan mutasi baru pada domain A yang belum pemah dipublikasikan yaitu Y487F (rt YI4IF), D480N (rt Dl34N) dan N485S (rt Nl39S). Mutan Y487F ditemukan pada 5 pasien (3l,25%) yang sama persis dengan mutasi MSSOI. Domain A dan C mempunyai peranan pada binding nukleosida trifosfal, sehingga diperkirakan mutasi baru yang ditemukan pada domain A juga mempunyai kontribusi terhadap terjadinya resistensi lamivudin. Virus yang mengalami mutasi L526M + MSSZV tidak menunjukkan mutasi pada Y487F, tetapi mengalami mutasi pada D48ON dan N485S. Kesimpulan yang dapat diambil dari penelitian ini adalah : 1) Pada level genetik tidak terjadi perubahan atau mutasi gen dCK (ekson 2) yang berhubungan dengan resistensi lamivudin. 2) Pada gen P (domain RT) virus hepatitis B terdapat mutasi pada domain A, B dan C yang berhubungan dengan resistensi terhadap lamivudin.

Abstract
The resistance against lamivudine treatment in hepatitis B patients is a problem frequently encountered by physicians. Lamivudine resistance is usually associated with viral mutations especially in the YMDD region of P gene, the involvement of host factors however, was not studied yet so far. This investigation is designed to determine either host or viral factors responsible responsible for lamivudine resistance. The aim of this study are : 1) To understand the involvement of host dCK gene which code for deoxycytidine kinase in lamivudine resistance. 2) To understand the involvement of viral P gene which code for polymerase/reverse transcriptase in lamivudine resistance. The investigation was performed by means of Polymerase Chain Reaction (PCR) and direct sequencing methods.
The results indicate that dCK gene (exon 2) is relatively conserved. Unsignificant mutation (G33W) was found in only one patient who was sensitive to lamivudine treatment; while no mutations were fotmd in either patients resistance agains lamivudine treatment or normal population. A study on P gene (RT domain) of hepatitis B virus have found l (6,25 %) mutation on B domain as L526M (rt LISOM) and 6 (37.5 %) mutations on C domain as YMDD mutants composing of 5 (31.25 %) mutant M5501 (rt M204l) and 1 (6.25 %) mutant MSSOV (rt M204V). A mutant of MSSOV is also mutate on L526M. This study also discovered new mutations in A domain which have unpublished yet; thhey are Y487F (rt Y141F), D430N (rt D131N) and N485S (rt Nl39S). Y-487F mutants were found in 5 patients (31.25 %) who definitely similar to mutation of M550I. The A and C domain are responsible for nucleside triphosphate binding, therefore the mutation found in A domain is also considered to contribute to lamivudine resistance manifestation. Virus with mutation of L526 + M55 OV did not indicate mutation in Y487F, but mutated in D480N and N485S otherwise. The conclusion of this study are : 1) There are no changes or mutations of dCK gene (exon 2) associate to lamivudine resistance. 2) There are mutations on hepatitis B virus P gene (RT domain) present on A, B and C domain which are associated with resistance to lamivudine treatment.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2005
D709
UI - Disertasi Membership  Universitas Indonesia Library
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Yulia Ariani
"Latar belakang. Malformasi kongenital multipel (MKM) masih menjadi masalah besar di Indonesia, karena muncul sebagai penyebab kematian neonatal yang cukup signifikan. Faktor genetik adalah penyebab tersering MKM dan lebih dari 50% disebabkan oleh kelainan kromosom.
Tujuan. Tujuan penelitian ini adalah untuk mengetahui berbagai kelainan struktur kromosom yang berperan dalam kejadian MKM dan alur diagnosis MKM yang sesuai untuk Indonesia.
Metoda. Diagnosis klinis dengan menggunakan database merupakan tahap awal untuk membedakan known dan unknown MKM. Pemeriksaan G-banding menjadi pilihan lini pertama untuk unknown MKM. Pemeriksaan microarray merupakan pemeriksaan lanjutan bila tidak ditemukan kelainan pada pemeriksaan G-banding. Platform microarray yang dipilih adalah CytoSNP 850Kb dengan dua fungsi yaitu array-CGH dan SNP-array.
Hasil. Pasien MKM di Indonesia memiliki fenotip beragam dan bersifat multiorgan. Tiga fenotip tersering yang ditemukan pada subjek adalah hambatan pertumbuhan, mikrosefali, dan penyakit jantung bawaan. Empat puluh dari 94 subjek (42,6%) dapat ditegakkan diagnosis klinis dengan menggunakan database fenotip, 5 dengan etiologi infeksi dan 35 dengan etiologi genetik. Tujuh belas dari 49 subjek (34,7%) ditegakkan diagnosis etiologi dengan pemeriksaan G-banding. Tiga puluh dari 32 subjek (93,7%) didapat etiologi genetik dengan pemeriksaan microarray, dengan rincian sebagai berikut (a) 27 dari 30 subjek didapat dengan metoda array-CGH, dan (2) 3 dari 30 subjek didapat dengan metode SNP-array.
Diskusi. Berdasarkan temuan di atas dicoba disusun alur diagnosis etiologi untuk MKM di Indonesia sebagai berikut (a) menegakkan diagnosis klinis dengan menggunakan database fenotip, (b) melakukan pemeriksaan G-banding sebagai pemeriksaan lini pertama, (c) melakukan pemeriksaan microarray dengan pengklasifikasian sebagai berikut (i) gain/loss pathogenic (sindrom delesi/duplikasi), (ii) gain/loss likely pathogenic, (iii) VUS, (iv) menentukan adanya LoH, (v) mencari adanya gen imprinting dalam area LoH. (vi) menentukan adanya incidental finding.
Kesimpulan. Pendekatan diagnosis etiologi MKM di Indonesia membutuhkan tahapan yang tidak sama. Pertimbangan efektivitas yang dinilai dari tingkat deteksi dan pertimbangan efisiensi menjadi titik perhatian khusus. Metoda G-banding masih efektif sebagai lini pertama penegakkan diagnosis etiologi MKM di Indonesia. Pemeriksaan lini kedua adalah microarray. Penapisan awal secara klinis sangat menentukan tingkat deteksi kedua metoda tersebut.

Introduction. Multiple congenital malformations remain a major problem in Indonesia, as they emerge as a significant cause of neonatal death. Genetic factors are the most common cause of multiple multiple congenital malformation (MCM) and more than 50% are caused by chromosomal abnormalities both large and submicroscopic.
Aim. This study is aimed to investigate various chromosomal structural abnormalities that play a role in the incidence of MCM and to develop a suitable diagnostic flow of MCM in Indonesia
Method. Clinical diagnosis using a database is the initial stage to distinguish between known and unknown MCM. G-banding examination is the first line choice for the unknown MCM. Microarray examination is a follow-up examination if no abnormalities are found on the G-banding examination. The selected platform is CytoSNP 850Kb with two functions, CGH-array and SNP-array.
Results. Multiple congenital malformation patients in Indonesia have a diverse phenotype and included multi organ. The 3 most common phenotypes found in subjects are growth retardation, microcephaly, and congenital heart disease. Forty of the 94 subjects (42.6%) could be diagnosed clinically using a phenotype database, 5 with the etiology of infection and 35 with genetic etiology. Seventeen out of 49 subjects (34.7%) were diagnosed using G-banding examination. Thirty of 32 subjects (93.7%) diagnosed by microarray, with the following details (a) 27 of 30 subjects were obtained by the CGH-array method, and (b) 3 out of 30 subjects were obtained by the SNP-array method
Discussion. Based on the above findings, an etiological diagnosis flow for MCM in Indonesia is attempted as follows (a) establishing a clinical diagnosis using a phenotype database, (b) G-banding examination as a first-line examination, (c) microarray examination with the following classification ( i) pathogenic gain/loss (deletion/duplication syndrome), (ii) likely pathogenic gain/loss, (iii) variant of uncertain significance (VUS), (iv) determine the presence of LoH, (v) look for imprinting genes in the LoH area. (vi) determine the existence of incidental finding.
Conclusions. The etiological diagnosis approach of MKM in Indonesia requires different stages. Consideration of effectiveness assessed from the level of detection and consideration of efficiency is of particular concern. The G-banding method is still effective as the first line in establishing the etiological diagnosis of MCM in Indonesia. The second line test is microarrays. Initial clinical screening largely determines the detection rates of the two methods.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2019
D-pdf
UI - Disertasi Membership  Universitas Indonesia Library