Bethy S. Hernowo
Departement of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung

Published : 45 Documents
Articles

Pajanan Hipoksia Hipobarik Intermiten Menurunkan Metabolisme Anaerobik pada Tikus Jantan Spraque Dawley Hidayat, Achmad; Wiradisastra, Kahdar; Hernowo, Bethy S.; Achmad, Tri Hanggono
Jurnal Kedokteran Maranatha Vol 10, No 1 (2010)
Publisher : Universitas Kristen Maranatha

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Hipoksia hipobarik intermiten (HHI) sering dialami oleh para penerbang maupun awak pesawat. Jika hipoksia berlanjut, maka terjadi metabolisme anaerobik yang berlebihan dan gangguan pada mitokondria yang menyebabkan apoptosis. Penelitian ini bertujuan menganalisis efek pajanan HHI terhadap metabolisme anaerobik dengan mengukur ekspresi LDH dan kadar asam laktat sebagai indikator glikolisis serta ekspresi caspase-3 untuk melihat apoptosis sel. Dilakukan penelitian eksperimental selama periode Januari-April 2010 pada tikus jantan Spraque Dawley yang dipajankan HHI satu sampai empat kali dengan interval satu minggu. Satu kelompok kontrol tidak dipajankan hipobarik hipoksia sedangkan empat kelompok perlakuan dipajankan pada hipobarik hipoksia menggunakan type I chamber flight profile (ruang udara bertekanan rendah – RUBR) dengan modifikasi. Tekanan RUBR disesuaikan setara ketinggian 35.000 kaki selama 1-2 menit, 25.000 kaki selama 5 menit, dan 18.000 kaki selama 25 menit. Hasil penelitian menunjukkan kadar asam laktat menurun dengan semakin seringnya tikus terpajan HHI. Ekspresi protein LDH dan Caspase-3 dengan imunohistokimia dan Western Blot juga menurun dengan semakin seringnya tikus terpajan hipoksia hipobarik. Terdapat korelasi antara penurunan ekspresi protein LDH dan Caspase-3 (r = 0,522; p=0,0031). Simpulannya adalah pajanan HHI menurunkan metabolisme anaerobik yang ditandai dengan penurunan glikolisis dan apoptosis pada tikus jantan jenis Spraque Dawley.Kata kunci: hipoksia hipobarik intermiten, metabolisme anaerobik, LDH, asam laktat, Caspase-3
Hubungan Ekspresi Ki-67 dengan Grading Histopatologi Liposarkoma Afiati, -; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 45, No 3 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Liposarkoma merupakan salah satu tumor ganas jaringan lunak dan terbanyak ditemukan pada usia dewasa antara dekade 5 dan 7 serta jarang terjadi pada usia anak. Liposarkoma sering terjadi pada ekstremitas bawah (fosa poplitea dan paha bagian tengah), retroperitoneal, perirenal, mesenteric region, dan area bahu. Penelitian ini bersifat retrospektif dari 30 kasus liposarkoma yang diambil dari data Departemen Patologi Anatomi Rumah Sakit Dr. Hasan Sadikin Bandung yang terdiri atas 20 kasus low-grade liposarcoma dan 10 kasus high-grade liposarcoma. Penelitian dilakukan periode Februari–Mei 2011. Dilakukan pemeriksaan khusus imunohistokimia dengan menggunakan antibodi monoklonal Ki-67 yang berfungsi sebagai marker proliferasi sel, dengan tujuan melihat ekspresi Ki-67 dan apakah terdapat hubungan antara ekspresi Ki-67 dan grading histopatologi liposarkoma. Ekspresi dan intensitas warna Ki-67 pada sel tumor dibagi menjadi sangat rendah (<20% positif), rendah (20– 50% positif), sedang (50–80% positif) dan tinggi (>80% positif), sedangkan untuk intensitas warna Ki-67 dibagi menjadi lemah, sedang, dan kuat. Terdapat perbedaan yang signifikan antara ekspresi dan intensitas Ki-67 pada low-grade liposarcoma dan high-grade liposarcoma (p<0,0001). Simpulan, ekspresi Ki-67 yang tinggi dengan intensitas yang kuat hanya didapatkan pada high-grade liposarcoma yang juga berhubungan dengan progresivitas tumor. [MKB. 2013;45(3):187–91]Correlation of Ki-67 Expression with Histopathological Grading ofLiposarcomaLiposarcoma, a malignant tumor of mesenchymal origin, was one of the most common sarcomas of adults and occurs primarily in the fifth through seventh decades of life. The occurrence in children was rare. Liposarcoma were occur most frequently in the lower extremities (popliteal fossa and medial thigh), retroperitoneal, perirenal, mesenteric region and shoulder area. Retrospective study was conducted by reviewing the data from Pathology Anatomy Department Dr. Hasan Sadikin Hospital Bandung. There were 30 cases of liposarcoma, whereas lowgrade of liposarcoma 20 cases and high-grade of liposarcoma 10 cases. Research was done during February–May 2011. Immunohistochemical staining examination used monoclonal antibody Ki-67 as marker cell proliferation with the aim for looking Ki-67 expression and related with histopatholgy grade of liposarcoma. The tumor cells which showed Ki-67 expression were divided into very low (<20% positive), low (20–50% positive), moderate (50–80% positive) and high (>80% positive), whereas the intensity of Ki-67 staining was into weak, moderate and strong. There were significant differences between the Ki-67 expression and intensity level according to the histopathological types of liposarcoma (p<0.0001). In conclusions, Ki-67 expression increases with strong intensity of Ki-67 only in high-grade liposarcoma, so relates with progressivity of tumor. [MKB. 2013;45(3):187–91]DOI: http://dx.doi.org/10.15395/mkb.v45n3.149 
Ekspresi Bcl-2 dan Caspase-3 Pascapaparan Hipoksia Hipobarik Intermiten Hidayat, Achmad; Wiradisastra, Kahdar; Hernowo, Bethy S.; Achmad, Tri Hanggono
Majalah Kedokteran Bandung Vol 43, No 4 (2011)
Publisher : Fakultas Kedokteran, Universitas Padjadjaran

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Abstract

Hipoksia hipobarik intermiten sering dialami oleh awak pesawat, karena selama di dalam kabin pesawat bernapas dengan tekanan udara yang lebih rendah. Tubuh akan beradaptasi dengan cara mengikat oksigen lebih banyak dan juga mengurangi dampak hipoksia. Fungsi mitokondria akan terganggu pada hipoksia, yaitu permiabilitas membran luar mitokondria karena protein Bcl-2 menurun. Jika hipoksia berlanjut akan terjadi kebocoran membran mitokondria, pelepasan sitokrom-c, dan proses apoptosis berlangsung. Penelitian ini bertujuan menganalisis protein Bcl-2 sebagai antiapoptosis dan caspase-3 sebagai indikator apoptosis akibat paparan hipoksia hipobarik intermiten. Dilakukan penelitian eksperimental pada tikus jantan Spraque Dawley periode Januari–April 2010 dengan melakukan paparan hipoksia hipobarik intermiten satu sampai empat kali dengan interval satu minggu. Jantung tikus dijadikan spesimen untuk dilakukan pemeriksaan ekspresi protein dengan pulasan imunohistokimia di Departemen Patologi Anatomi RS Dr. Hasan Sadikin Bandung dan western blot di Bagian Biomolekuler FK Universitas Indonesia Jakarta. Ekspresi protein Bcl-2 meningkat sesuai dengan frekuensi paparan hipoksia hipobarik intermiten, sebaliknya ekspresi protein caspase-3 menurun (rs=-0,448, p=0,013). Dari penelitian ini dapat disimpulkan bahwa terjadi penurunan tingkat apoptosis akibat paparan hipoksia hipobarik intermiten, hal ini disebabkan mekanisme adaptasi natural yang ditandai dengan menurunnya apoptosis sel dan secara tidak langsung akan memberi efek kardioprotektif. [MKB. 2011;43(4):166–70].Kata kunci: Apoptosis, Bcl-2, caspase-3, hipoksia hipobarik intermitenBcl-2 and Caspase-3 Expression Post Exposure of Intermittent Hypobaric HypoxiaIntermittent hypobaric hypoxia often suffered by cabin crew due to the fact that they are breathing lower pressured air inside the plane cabin. Human body will adapt by binding more oxygen and reducing hypoxia effect. Mitochondria function will be irritated by hypoxia which affect, outer mithochondrial membrane permeability due to decrease of Bcl-2 protein. Later on if hypoxia continues mitochondrial membrane will leaked cytocrome-c will released and apoptotic pathway will occur. The purpose of this study was to analyze Bcl-2 protein as antiapoptosis and caspase-3 as apoptosis indicator of intermittent hypobaric hypoxia exposure. Experimental study >was subjected to Spraque Dawley male mice during January–April 2010 by exposing them to several intermittent hypobaric hypoxias (one to four treatment) in an interval of one week. Protein expression on mice heart cell were detected by immunohistochemistry in the Department of Pathology Anatomy Padjadjaran University-RS Dr. Hasan Sadikin Bandung and western blot methods in Department Biomolecullar Indonesia University Jakarta. Bcl-2 protein expressions increased according with the frequency of intermittent hypobaric hypoxia exposures while a reverse trend was found for caspase-3 protein expressions (rs=-0.448, p=0.013). From the study it can be concluded that apoptosis will be decreased as a result of intermittent hypobaric hypoxia exposures, which occurred from natural adaptation mechanism indicated by decrease of cell apoptosis and cardio protective effect will be emerged. [MKB. 2011;43(4):166–70].Key words: Apoptosis, Bcl-2, caspase-3, intermittent hypobaric hypoxia
HUBUNGAN STATUS INSTABILITAS MIKROSATELIT DAN EKSPRESI P53 DENGAN ETIOPATOLOGI ADENOKARSINOMA KOLOREKTAL PADA ORANG INDONESIA DI KELOMPOK USIA KURANG DARI 40 TAHUN Lukman, Kiki; Dewayani, Brigitta M.; Hernowo, Bethy S.; Hanafi, Basrul; Achmad, Tri Hanggono; Sugandi, Suwandi
Indonesian Journal of Applied Sciences Vol 2, No 1 (2012)
Publisher : Universitas Padjadjaran

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Epidemiologically, the percentage of colorectal adenocarcinoma (CRC) in the age group ≤40 years old in Indonesia is higher than in the West European, North American and other developed Asian countries with different clinico-pathological features. In the afromentioned countries, the carcinogenesis pathway of this group is hereditary which show high microsatellite instability (MSI), whereas the age group >40 years old is sporadic of which show chromosomal instability (CIN) with the mutation of p53 gene. To elucidate the carcinogenesis pathway with its molecular characteristics of this group among Indonesians, a cross sectional study was conducted by performing the immunohistochemical detection of MLH1 and MSH2 expression (MSI status), and mutated p53 gene expression (CIN) in the CRC group ≤40 years old and >40 years old at Dr. Hasan Sadikin Hospital, Bandung, from May 2008 until November 2009. Thirty nine CRC patients, consisting of 22 patients of  ≤40 years old and 17patients >40 years old, were eligible for this study. The CRC patients of ≤40 years old showed 4 MSI high,  1 MSI lowand 17 MSS (microsatellite stable), associated with 10 p53 positive and 12 p53 negative status. In the CRC group of >40 years old, there was no MSI high, but 4 MSI low and 13 MSS were found, associated with 11 p53positive and 6 p53negative status. There was no significant difference with regards to the association between MSI status and p53 expression in both groups (p MSI=0.95, p p53=0.23).
Peran Ekstrak Etanol Topikal Daun Mengkudu (Morinda citrifolia L.) pada Penyembuhan Luka Ditinjau dari Imunoekspresi CD34 dan Kolagen pada Tikus Galur Wistar Rahmayani S., Indah Puti; Maskoen, Ani Melani; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Luka akan menimbulkan masalah jika penanganannya kurang baik sehingga menyebabkan luka kronik. Mengkudu (Morinda citrifolia L.) merupakan tanaman khas daerah tropis termasuk Indonesia, yang buah, daun, dan akarnya sering digunakan dalam pengobatan tradisional, di antaranya untuk menyembuhkan luka. Penelitian dengan rancangan eksperimental sederhana ini bertujuan untuk mengetahui efek penggunaan ekstrak etanol daun mengkudu terhadap penyembuhan luka pada pemberian topikal, dengan melihat gambaran histopatologis yang terdiri atas sel fibroblas, infiltrasi sel inflamasi, imunoekspresi cluster of differentiation 34 (CD34), dan deposisi kolagen. Penelitian dilakukan di laboratorium Farmakologi dan Patologi Anatomi RS Dr. Hasan Sadikin Bandung pada November 2010‒September 2011. Penelitian ini dilakukan pada 36 tikus dengan membuat eksisi pada punggung tikus. Kemudian tikus-tikus tersebut dibagi menjadi 2 kelompok yaitu kelompok kontrol dan perlakuan ekstrak etanol daun mengkudu topikal pada luka. Jaringan luka tiap kelompok diamati secara mikroskopis pada hari ke-3, 7, dan 14. Hasil penelitian menunjukkan penyembuhan luka kelompok perlakuan cenderung lebih baik, dilihat pada data hari ke-3, 7, dan 14 pada semua parameter. Uji statistik Mann-Whitney pada tingkat kepercayaan 95% (p<0,05) untuk jumlah fibroblas, infiltrasi sel inflamasi, imunoekspresi CD34, dan kolagen berturut-turut p=0,319; p=0,290; p=0,251; dan p=0,245. Simpulan, ekstrak etanol topikal daun mengkudu cenderung bermanfaat pada penyembuhan luka, walaupun secara statistik tidak bermakna. [MKB. 2013;45(4):226–33]Kata kunci: CD34, daun mengkudu, kolagen, penyembuhan lukaRole of Noni (Morinda citrifolia L.) Leaf Ethanolic Extract TopicalApplication on Wound Healing Examined from CD34 Immunoexpression and Collagen on Wistar RatsProblems in wound healing occurred if proper care is not given and the wound develops into a chronic wound. Noni (Morinda citrifolia L.) is one of the most common plants in tropical areas, including Indonesia, which fruit, leaves dan root are used in traditional treatment, for example wound healing. This experimental research with post test-only control group design identified the effect of topical application of noni leaves ethanol extract on wound healing by examining the histopathological appearance of fibroblas count, inflammatory cell infiltration, cluster of differentiation 34 (CD34) immunoexpression, and collagen deposition. The research was performed between November 2010 until September 2011 at the Pharmacology and Pathology Anatomy laboratories of Dr. Hasan Sadikin General Hospital Bandung. Excisions were made on each back of the rat of the 36 rats that were divided into control and test groups where the test group received topical application of noni leaves ethanol extract. The wound was examined on day 3, 7, and 14 using a light microscope. The result showed a tendency of better wound healing in the test group for all parameters based on the data on day 3, 7, and 14. Mann-Whitney Test with 95% confidence interval (p<0.05) showed that the p value for fibroblast count, inflammation cell infiltration, CD34 immunoexpression and collagen subsequently were p=0.319, p=0.290, p=0.251, and p=0.245, respectively. In conclusion, topical application of noni leaves ethanol extract has a benefit on wound healing although the results are not statistically significant. [MKB. 2013;45(4):226–33]Key words: CD34, collagen, noni leaves, wound healing DOI: http://dx.doi.org/10.15395/mkb.v45n4.169
Hubungan Imunoekspresi CD34 dengan Gradasi dan Stadium (Duke) pada Adenokarsinoma Kolorektal Yulianti, Herry; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Karsinoma kolorektal umum terjadi di Eropa Barat Laut dan Amerika Utara, tetapi rendah di Afrika, Asia, dan Amerika Selatan. Di Indonesia, karsinoma kolorektal merupakan masalah kesehatan masyarakat dan merupakan tiga penyakit kanker terbanyak. Angiogenesis adalah pertumbuhan dan proliferasi pembuluh darah baru dari pembuluh darah yang sudah ada. Secara imuno histokimia, mikrovaskular dapat diidentifikasi dengan menggunakanmonoklonal cluster of differentiation (CD34) antibodi. Pada beberapa penelitian, microvascular density (MVD) berhubungan dengan gradasi histologi, stadium, metastasis, dan prognosis tumor. Tujuan penelitian ini untuk mengetahui hubungan ekspresi CD34 dengan gradasi dan stadium (klasifikasi Duke) pada karsinoma kolorektal. Metode penelitian adalah cross sectional terhadap 40 kasus adenokarsinoma kolorektal yang berasal dari Departemen Patologi Anatomi Rumah Sakit Dr. Hasan Sadikin Bandung-Fakultas Kedokteran Universitas Padjadjaran tahun 2004–2005. Potongan blok parafin dari jaringan kolorektal karsinoma diwarnai dengan hematoksilin eosin untuk evaluasi histologi dan imunohistokimia menggunakan monoclonal CD34 antibody. Penghitungan MVD yang imunoreaktif dilakukan di bawah mikroskop cahaya dengan pembesaran 400x, dihitung rata-rata pada 5 tempat daerah neovaskularisasi yang paling padat. Hasil penelitian menunjukkan hubungan yang signifikan MVD dengan stadium (p<0,01) dan tidak ada hubungan yang signifikan antara MVD dan gradasi (p<0,05). Simpulan, hubungan MVD dengan kedalaman invasi dan metastasis ke kelenjar limfe yang dinilai dengan klasifikasi Duke dan CD34 dapat digunakan untuk memprediksi prognosis, memperkirakan kemungkinan metastasis melalui pembuluh darah, dan memprediksi respons terhadap terapi antiangiogenik. [MKB. 2013;45(4):240–4]Kata kunci: Adenokarsinoma kolorektal, CD34, gradasi, klasifikasi DukeCorrelation between CD34 Immunoexpression and Colorectal Adenocarcinoma Grade and Stage (Duke) Carcinoma colorectal is commonly found in Nortwest Europe and North America, but not frequently found in Africa, Asia and South America. Colorectal cancer (CRC) is a public health problem in Indonesia and currently ranks among the three most common cancers. Angiogenesis is the growth and proliferation of new blood vessels from existing vasculature. Microvessels were identified immunohistochemically using monoclonal cluster of differentiation (CD34) antibody. Several studies have noted that microvascular density (MVD) correlates with stage of disease, histological grade, metastasis, and prognosis in cancers. The aim of this study was to explore the relation between CD34 immunoexpresion and grade and stage (Duke classification) in colorectal adenocarcinoma. This is a cross sectional study with 40 colorectal carcinoma cases from Department of Pathology Anatomy, Dr. Hasan Sadikin General Hospital/Faculty of Medicine, Universitas Padjadjaran Bandung during 2004−2005. A section from paraffin embedded tissue of colorectal carcinoma was stained with hematoxylin eosin for histological and immunohistochemical evaluations using monoclonal CD34 antibody. Microvascular density was counted in five tumor areas with most intensive neovascularization using 400x field light microscopy. A significant correlation was found between the MVD and stage (p<0.01) while no significant relationship found between MVD and different grade (p<0.05). In conclusion, correlations are found between MVD with tumor invation depth and lymph node metastases determined by the Duke’ staging system and CD34 can be used to predict prognosis, possibility of hematogenous metastases and responses to antiangiogenic therapy. [MKB. 2013;45(4):240–4]Key words: Adenocarcinoma colorectal, CD34, Duke clasification, grade DOI: http://dx.doi.org/10.15395/mkb.v45n4.171
Ekspresi Protein B-RAF Mutan pada Karsinoma Tiroid Papilifer yang Bermetastasis ke Kelenjar Getah Bening Regional Achmad, Dimyati; Sebastian, Jeremy; Hernowo, Bethy S.; Rizki, Kiki A.
Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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AbstrakKarsinoma tiroid papilifer (KTP) dapat tumbuh progresif dan sekitar 33−61% kasus secara klinis telah metastasis ke kelenjar getah bening (KGB) regional pada saat diagnosis ditegakkan. Mutasi gen B-RAF dihubungkan dengan sifat biologis progresivitas KTP. Mutasi gen B-RAF akan mengkode protein B-RAF mutan yang bertindak sebagai regulator sentral pada jalur mytogen activated-pathway kinase (MAPK) dalam proses proliferasi dan dediferensiasi. Mutasi gen B-RAF dapat diidentifikasi pada tingkat deoxyribosenucleic acid (DNA), ribonucleic acid (RNA), dan protein. Masih terdapat kontroversi antara hubungan mutasi B-RAF dan metastasis KGB regional. Tujuan penelitian ini untuk mengetahui hubungan protein B-RAF mutan dengan metastasis ke KGB regional pada KTP. Penelitian ini merupakan penelitian observasional rancangan kuantitatif, studi kasus kontrol berpasangan. Penelitian dilakukan di Subbagian Bedah Onkologi, Kepala dan Leher, Departemen Ilmu Bedah dan Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/ Rumah Sakit Dr. Hasan Sadikin Bandung. Sampel penelitian terdiri atas 38 kasus KTP dengan metastasis dan 38 kasus kontrol tanpa metastasis ke KGB regional yang dirawat di Rumah Sakit Dr. Hasan Sadikin Bandung pada periode Januari 2003−Desember 2010 dan dipilih berdasarkan proses matching. Masing-masing kelompok diperiksa B-RAF mutan dengan metode imunohistokimia. Hubungan antara tiap variabel bebas dan variabel tergantung diuji menggunakan analisis bivariat Uji McNemar.Hasil penelitian menunjukkan protein B-RAF mutan memiliki hubungan bermakna (p=0,023) dengan metastasis ke KGB regional pada KTP. Terdapat protein B-RAF mutan pada KTP mempunyai risiko untuk metastasis ke KGB regional sebesar 5,92 kali dibandingkan dengan tanpa mutasi B-RAF. Penelitian ini juga menunjukkan prevalensi B-RAF mutan sebesar 65,8% (32 kelompok kasus dan 18 kelompok kontrol). Simpulan, protein B-RAF mutan memiliki hubungan dengan metastasis ke KGB regional pada KTP. [MKB. 2013;45(4):245–50]Kata kunci: Imunohistokimia, karsinoma tiroid papilifer, metastasis ke KGB regional, mutasi B-RAFMutant B-RAF Protein Expression in Regional Lymph Node Metastasized Papillary Thyroid CarcinomaPapillary thyroid carcinoma (PTC) can become progressive and in about 33−61% of cases it has metastasized to regional lymph nodes at diagnosis. Mutation of B-RAF gene correlated with the biological characteristic of lymph node progressivity. Mutation of B-RAF will encode mutant B-RAF protein which acts as the central regulator on mytogen activated-pathway kinase (MAPK) pathway in terms of proliferation and dedifferentiation processes. B-RAF gene mutation can be identified at deoxyribosenucleic acid (DNA), ribonucleic acid (RNA) and protein levels. There are still controversies in corelation between B-RAF mutation and regional lymph node metastasis. The purpose of this study was to discover the correlation between mutant B-RAF protein and regional lymph node metastasis on PTC. This is a quantitative observational paired case-control study. The study was conducted at the Surgical Oncology, Head and Neck Division Departement of Surgery and Pathology Anatomy Departement, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung in April 2011–January 2012. The sample consisted of 38 PTC cases with metastasis and 38 control cases without regional lymph node metastasis treated in Dr. Hasan Sadikin Hospital between January 2003–December 2010 which have been selected based on the matching process. Each group was examined using the immunohistochemistry method. Correlation between each dependent and non-dependent variables were tested using McNemar bivariate analysis. The results showed that mutant B-RAF protein have a significant correlation (p=0.023) with lymph node metastasis in PTC. The risk of metastasis in B-RAF mutant group was 5.92 times higher than without mutation. This study also showed that from 76 PTC cases studied, the prevalence of mutant B-RAF was about 65.8% (32 in cases and 18 in control group). In conclusion, there is a correlation between mutant B-RAF protein and regional lymph node metastasis in papillary thyroid carcinoma. [MKB. 2013;45(4):245–50]Key words: B-RAF mutation, immunohystochemistry, papillary thyroid carcinoma, regional lymph node metastasis DOI: http://dx.doi.org/10.15395/mkb.v45n4.200
Hubungan Faktor Risiko, Status Instabilitas Mikrosatelit, dan Ekspresi P53 dengan Karsinogenesis Adenokarsinoma Kolorektal pada Orang Indonesia Lukman, Kiki; Yuniasari, Laely; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 44, No 4 (2012)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Berbeda dengan berbagai negara lain, karakteristik molekuler adenokarsinoma kolorektal (AKK) pada orang Indonesia di dalam kelompok usia ≤40 tahun memiliki kesamaan dengan kelompok usia >40 tahun, dan keduanya berada pada jalur karsinogenesis sporadik. Untuk mengetahui hubungan karakteristik molekuler dengan berbagai faktor risiko AKK, dilakukan penelitian potong lintang yang mempelajari hubungan berbagai faktor risiko, status instabilitas mikrosatelit (IM), dan ekspresi P53 (instabilitas kromosom=IK) pada 39 penderita AKK yang memenuhi kriteria inklusi di Rumah Sakit Dr. Hasan Sadikin Bandung dalam periode Maret 2009−Maret 2010. Diperoleh masing-masing 21 dan 18 penderita AKK laki-laki dan perempuan, serta 17 dan 22 penderita berusia >40 dan ≤40 tahun. Dilakukan pemeriksaan imunohistokimia ekspresi gen MLH1, MSH2, dan p53 untuk menentukan status IM dan IK. Hasilnya adalah penderita AKK ≤40 tahun menunjukkan 4 IM tinggi, 1 IM rendah, dan 17 IM negatif, serta 10 status P53 positif dan 12 P53 negatif. Penderita AKK >40 tahun menunjukkan 4 IM rendah, dan 13 IM negatif, yang disertai oleh 11 status P53 positif dan 6 status P53 negatif. Pada kedua kelompok tersebut tidak didapatkan perbedaan yang bermakna (p>0,05) dalam pola hubungan berbagai faktor risiko AKK dengan karakteristik molekulernya. Pola diet tinggi lemak dan protein, rendah serat, overweight, merokok, dan aktivitas fisik rendah ditemukan sebagai faktor risiko yang berperan pada kedua kelompok tersebut. Simpulan, mayoritas penderita AKK pada orang Indonesia memiliki klasifikasi molekuler berupa status IK tinggi dan status IM rendah, serta berhubungan dengan faktor risiko diet tinggi lemak dan protein, rendah serat, overweight, merokok, dan aktivitas fisik rendah. [MKB. 2012;44(4):245–52]Kata kunci: Ekspresi P53, faktor risiko, instabilitas mikro-satelit, karsinogenesis adenokarsinoma kolorektalThe Association of Risk Factors, Microsatellite Instability, and P53 Expression in the Carcinogenesis of Colorectal Adenocarcinoma among IndonesianDifferent from developed countries, molecular characteristic of colorectal adenocarcinoma (CRC) among Indonesians in the age group of ≤40 years old is mostly similar compared to the CRC of the age group of >40 years old, and both are sporadic cancers. To know the association of molecular characteristic with the risk factors of CRC, a cross sectional study was conducted to analyze the association of risk factors, microsatellite instability (MSI) and P53 expression (chromosomal Instability=CIN) status in 39 consecutive CRC patients who were eligible for this study at Dr Hasan Sadikin Hospital, from March 2009 until March 2010. They consisted of 21 male and 18 female patients. Of them, there were 17 and 22 patients with>40 and≤40 years of age, respectively. The immuno-histochemistry examinations for the expression of mutated MLH1, MSH2 and p53 genes were conducted to determine the CIN and MSI status. The results showed that the CRC ≤40 years of age had 4 MSI high, 1 MSI low, and 17 MSI negative, associated with 10 P53 positives and 12 p53 negatives. By contrast, in the CRC >40 years of age the MSI was low and negative in 4 and 13 cases, respectively. They were associated with 11 and 6 of p53 positive and negative status, respectively. Between the two groups, there were no significant differences with regards to the association pattern between the risk factors and their molecular characteristics (p>0.05). Conclusions, majority of CRC patients among Indonesian show a molecular classification of high CIN and low MSI, and is associated with risk factors of high fat and protein, low fiber dietary intake, overweight, smoking, and low physical activitis. [MKB. 2012;44(4):245–52]Key words: Carcinogenesis of colorectal carcinoma, expression of P53, microstallite instability, risk factors DOI: http://dx.doi.org/10.15395/mkb.v44n4.216
Myocardial damage after continuous aerobic and anaerobic exercise in rats Flora, Rostika; Ferdinal, Frans; Hernowo, Bethy S.; Wanandi, Septelia I.; Sadikin, Mohamad; Freisleben, Hans-Joachim
Medical Journal of Indonesia Vol 22, No 4 (2013): November
Publisher : Faculty of Medicine Universitas Indonesia

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Abstract

Background: Regular physical activity is highly recommended in preventive, curative, and rehabilitative programs in order to promote health, especially cardiovascular health. However, physical activity can also cause sudden death. In athletes, sudden death may occur during sport competitions, with myocardial infarction as the most common etiology. It is suspected that continuous training without any rest-day play a role in cardiac muscle damage and sudden death during competition. Our study was aimed to learn about cardiac muscle adaptation on continuous aerobic and anaerobic physical activity without any rest-day. Methods: The specimens in our study were cardiac muscle tissue obtained from rats that had performed aerobic and anaerobic physical activity on treadmill for 1, 3, 7, and 10 days without any rest-day. Blood gas analysis and hematological assessment were used as parameters of systemic adaptation to hypoxia during physical activity. Moreover, histopathology of cardiac muscle tissue was performed as parameter for cardiac muscle damage.Results: The results showed that aerobic and anaerobic physical activity caused a systemic hypoxic condition and triggered adaptation responses. Cardiac muscle damage occurred on the 10th day in both treatment groups, with more severe damage observed in the group with anaerobic physical activity. The tissue protein level in the anaerobic group increased progressively on the 10th day.Conclusion: Physical activity may result in hypoxia and systemic adaptation. Aerobic and anaerobic physical activities performed for 10 days without any rest-day may cause cardiac muscle damage. (Med J Indones. 2013;22:209-14. doi: 10.13181/mji.v22i4.601)Keywords: Cardiac muscle, cardiac muscle damage, histopathology, physical activity
Hubungan BRAF V600E dan EGFR dengan Metastasis ke Kelenjar Getah Bening pada Adenokarsinoma Kolorektal Ariyanni, Fenny; Hassan, Abdul Hadi; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 47, No 3 (2015)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Adenokarsinoma kolorektal adalah tumor ganas epitel kolorektal yang berdiferensiasi kelenjar. Metastasis ke kelenjar getah bening sangat memengaruhi prognosis dan penatalaksanaan penderita karsinoma kolorektal. Penelitian ini untuk mengetahui hubungan BRAF V600E dan EGFR dengan metastasis ke kelenjar getah bening. Disain penelitian potong lintang analisis kategorik tidak berpasangan terhadap kasus adenokarsinoma kolorektal yang dipilih secara konsekutif dari blok parafin massa tumor yang dilakukan pemeriksaan imunohistokimia BRAF V600E dan EGFR di Departemen Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/RSUP Dr. Hasan Sadikin Bandung pada bulan Februari sampai Juni 2014. Hasil penelitian menunjukkan tidak terdapat hubungan antara imunoekspresi BRAF V600E positif dan metastasis ke kelenjar getah bening dengan p=0,269 (uji chi-kuadrat) dan imunoekspresi EGFR yang positif dengan metastasis ke kelenjar getah bening dengan p=0,713 (uji chi-kuadrat). Imunoekspresi BRAF V600E dan EGFR yang positif tidak berhubungan dengan metastasis ke kelenjar getah bening, p=0,427 (Uji Fisher Exact). BRAF dan EGFR berperan pada epithelial mesencymal transition sehingga sel mampu bermigrasi, tetapi kemampuan migrasi ini tidak berperan pada kejadian metastasis tumor adenokarsinoma kolorektal ke kelenjar getah bening. Simpulan, imunoekspresi BRAF V600E dan EGFR pada adenokarsinoma kolorektal tidak dapat digunakan sebagai petanda agresivitas tumor adenokarsinoma kolorektal. [MKB. 2015;47(3):179–85]Kata kunci: Adenokarsinoma, BRAF V600E, EGFR, kelenjar getah bening, kolorektalAssociation of BRAF V600E and EGFR with Lymph Nodes Metastasis in Colorectal AdenocarcinomaAbstractColorectal adenocarcinoma is an epithelial malignant tumor with glandular differentiation. Lymph node metastasize affects the prognosis and management of colorectal carcinoma patients. In this study, association of BRAF V600E and EGFR with metastasis of the lymph nodes was investigated. This was a cross sectional study with unpaired categorical analysis of colorectal adenocarcinoma obtained from archival paraffin blocks from consecutively selected samples. The blocks were stained by BRAF V600E and EGFR antibody at the Department of Anatomical Pathology, Faculty of MedicineUniversitas Padjadjaran/Dr. Hasan Sadikin General Hospital during the period of February to June 2014. There was no association between positive BRAF V600E immunoexpression  and lymph node metastasis, p=0.269 (p>0.05, chi-square test). Similarly, there was no association between positive EGFR immunoexpression and lymph node metastasis, p=0.713 (p>0.05, chi-square test). Positive BRAF V600E immunoexpresion and positive EGFR immunoexpression also had no association with lymph node metastasis, p=0.427 (Fisher Exact test). BRAF and EGFR may play a role in the epithelial mesencymal transition to increase cell migration and invasion. However, in colorectal adenocarcinoma, BRAF V600E and EGFR were not associated with lymph node metastasis. In conclusions, positive BRAF V600E immunoexpression and positive EGFR immunoexpression in colorectal adenocarcinoma should not be used as markers formetastazing potentials of colorectal adenocarcinoma tumors. [MKB. 2015;47(3):179–85]Key words: Adenocarcinoma, BRAF V600E, colorectal, EGFR, lymph node DOI: 10.15395/mkb.v47n3.600