Hardyanto Soebono
Department Of Dermatology And Venereology, Faculty Of Medicine, Public Health, And Nursing Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta

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T cell and B cell reactivities of leprosy patients and their contacts against antigens or epitopes Mycobacterium leprae Hardyanto Soebono, Hardyanto Soebono
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 27, No 03 (1995)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

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Abstract

This study was aimed at evaluating the T cell and B cell reactivity against Mycobacterium leprae antigens or epitopes among leprosy patients and their household contacts in the Indonesian population. Through this study, M. leprae epitopes (either protective or suppresive) will be identified and hopefully proved useful for the development of an effective leprosy vaccine in the future.Fifty-nine leprosy patients consisting of 34 tuberculoid type (TT/BT) and 24 lepromatous type (LUBL) at Dr. Sardjito General Hospital Yogyakarta and 50 household contacts were recruited for this study. After the informed consent was given, 20 ml venous blood was drawn from each subject for assays of the T cell and B cell reactivities. The T cell reactivity was tested by lymphocyte transformation (LTT) and the B cell reactivity was tested serologically by EUSA. M. leprae antigen, PGL-1 and some recombinant proteins (65 kD, 30 kD, 45 kD and 43 kD) were used as antigens in both assays. In addition, Phytohemagglutinin (PHA) and lnterleukin-2 (IL-2) were used as mitogens in the LTT. Statistical analysis was done by using One way ANOVA and Chi-square tests.The results showed that cellular immune deficiency in LUBL patients was found to be specific to the M. leprae antigen, but not to mitogens and other antigens. The T-lymphocyte of the patients (either TT/BT or LUBL) and healthy contacts demonstrated very low reactivities againts all recombinant antigens. On the other hand, the sera of LL/BL leprosy patients reacted significantly against all antigens, most strikingly against PGL-I and 43 recombinant protein of M. leprae. Whereas, the sera of TT/BT patients and healthy contacts showed no or least reactivity against those antigens. These data indicate that although in a small proportion M. leprae recombinant proteins of 65 kD, 30 kD, 45 kD and 43 kD are recognized by T-cell of leprosy patients and healthy contacts. These antigens contain more B-cell epitopes rather than T-cell epitopes. So, these antigens should be eliminated. as soon as a possible candidate in the development of any leprosy vaccine.Key words: leprosy - T-cell and B-cell - Mycobacterium leprae antigen - ELISA - tuberculoid and lepromatouse types
Association between HLA-DQ alleles and Leprosy in Indonesia Javanese population Hardyanto Soebono, Hardyanto Soebono
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 28, No 01 (1996)
Publisher : Universitas Gadjah Mada

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Abstract

Previous studies showed that susceptibility to leprosy and antibody response toward M. leprae in Javanese population was under control of HLA-DR alleles. To investigate whether this susceptibility was also associated with HLA-DQ, the study had been continued with phenotyping of HLA-DQ alleles and antibody assay to the same population which consisted of 79 leprosy patients, 41 tuberculoid (TT/BT) and 38 lepromatous (LL/BL) type, and 50 healthy controls. The HLA-DQ typing had been performed by using a sequence specific oligonucleotyping (SSO). method, while the anti M. leprae antibody had been tested by ELISA and INHIBITION-ELISA.The results show that HLA-DQB501 is associated with leprosy, either tuberculoid or lepromatous type (OR 3.27; 95% Cl 1.42-7.60). When all HLA-DQ1 alleles are analyzed, a significant association is found only with lepromatous leprosy (OR 9.18; 95% Cl 1.89-86.30). IgG antibody anti 36 kD M. leprae is found to be associated with HLA-DQ102. The level of this antibody is higher in HLA-DQ102 positive individuals compared to those negative one (P). No correlation is found between HLA-DQ alleles and the seropositivity of either IgM or IgG.In conclusion, the susceptibility to leprosy in this population is also controlled by genes in HLA-DQ locus. This study also supports the previous findings that HLA-DQ1 is a universal marker for the susceptibility to lepromatous leprosy, while the infection with M. leprae per se is not controlled by HLA genetic factor.Key words : leprosy - M. /eprae - genetic factor - HLA-DQ - HLA-DQ1 - HLA-DQB501
Effect of Oxidative Stress on AhpC Activity and Virulence in katG Ser315 Thr Mycobacterium tuberculosis Mutant Rintiswati, Ning; Wibawa, Tri; Asmara, Widya; Soebono, Hardyanto
Indonesian Journal of Biotechnology Vol 16, No 2 (2011)
Publisher : Universitas Gadjah Mada

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AbstractMycobacterium tuberculosis strains resistance to INH is mainly caused by the alteration in several genesencoding the molecular targets. Mutation of katG at codon 315 especially Ser315Thr are responsible forINH resistance in a large proportion of TB cases. The aim of this study is to evaluate the influence of stressoxidative on AhpC activity of katG Ser315Thr of M.tuberculosis, and to find out the relation of AhpC and thevirulence of this mutant. The study design was laboratoric experimental, subjects of study were M.tuberculosisINH resistance strains, and the treatment were serial dose of H2O2. Eighty five M.tuberculosis INH resistantclinical strain were screened for mutation of katGSer315Thr by PCR/RFLP and characterized on the basis ofphenotypic properties (catalase activity and AhpC activity). AhpC activity of katG Ser315Thr M.tuberculosisstrains in response to oxidative stress condition was evaluated by culturing the strains on liquid culturemedium containing 1mM H2O2. To ascertain role of AhpC in the virulence of katGSer315Thr mutant strains, themutants were infected into human macrophages culture, and several indicator of virulence were observed (i.e:replication competence, and apoptosis induction on human macrophages). The results showed that katG Ser315Thr were identified in 23 (27,05%) of 85 INH resistance strains, all mutant strains had decrease of catalaseactivity. AhpC activity of katG Ser315Thr of M.tuberculosis increased significantly with increase of hydrogenperoxide dose. In addition , it has been shown that increased AhpC activity related to replication ability ofmutant, and reduction of apoptosis macrophages induction significantly. We conclude that the productionof AhpC of katG Ser315Thr M.tuberculosis induced by oxidative stress. There was a role of AhpC in virulenceof the M.tuberculosis katG Ser315Thr strains by replication capability and macrophages apoptosis.Keywords : katG Ser315Thr Mycobacterium tuberculosis- oxidative stress - AhpC - virulence
The role of Various Factors in the Therapeutic Response of Calcipotriol in Mild to Moderate Plaque Type Psoriasis Patients Hardyanto Soebono, Siti Aminah Tri Susila Estri Sunardi Radiono
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 39, No 02 (2007)
Publisher : Universitas Gadjah Mada

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Background: Psoriasis is a chronic skin inflammation and proliferation disease. Natural history of psoriasis depends on the genetic, age, sex, history of treatment and psychosocial stressor. Calcipotriol is suitable for long-term therapy with good efficacy and safety and clinical response variability but its activity is influenced by ultraviolet.Objective: To know the factors that may influence treatment response of calcipotriol ointment on mild to moderate plaque type psoriasis.Method: Longitudinal study of two times daily calcipotriol ointment 0.005% treatment in the psoriasis patients. Factors that may influence the natural course (age, sex, history of psoriasis in family, history of therapy, MED, working location and psychological stressor) were identified. Evaluation of therapy was performed in the 8th weeks and based on the PASI and PDI. Correlation between treatment responses with various factors were analyzed by using student t-test, Pearson and Spearman correlations and multiple linear regression.Result: At the end of study, PASI was shown to decrease 38.45%, while PDI was 28.70% (p
Lepromatous leprosy mimicking systemic lupus erithematosus: a case report Kusumaningrum, Niken; Purnamawati, Schandra; Winarni, Dwi Retno Adi; Soebono, Hardyanto
Medical Journal of Indonesia Vol 28, No 1 (2019): March
Publisher : Faculty of Medicine Universitas Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (7167.123 KB) | DOI: 10.13181/mji.v28i1.1793

Abstract

The clinical manifestations of leprosy are highly variable, and the disease is notorious for being “a great imitator” of several other conditions. Leprosy may manifest with a variety of phenomena resembling those of autoimmune diseases. Herein, we report a 33-year-old male presenting with wounds on his left leg and hyperpigmented skin lesions all over his body. Six years earlier, the patient was diagnosed with systemic lupus erythematosus (SLE). However, therapy for SLE did not control his symptoms; instead, the patient developed features of leprosy, such as anesthetic skin lesions, nerve enlargement, and tenderness. Tests for antinuclear antibodies and anti-double stranded DNA antibodies were negative. Slit-skin smear showed a bacterial index of 6+ and morphological index of 10 %. Lupus band test results were negative. Histological findings were compatible with lepromatous leprosy. The clinical and serological similarities between leprosy and SLE may lead to erroneous diagnosis. Thus, clinicians should be aware of this characteristic for correct diagnosis.
PENGEMBANGAN DIAGNOSIS TUBERKULOSIS PADA HEWAN KESAYANGAN ANJING MENGGUNAKAN ANTIGEN SPESIFIK Mycobacterium tuberculosisESAT-6 DAN CFP-10 Tjahajati, Ida; Asmara, Widya; Soebono, Hardyanto
Jurnal Kedokteran Brawijaya Vol 23, No 2 (2007)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1627.133 KB) | DOI: 10.21776/ub.jkb.2007.023.02.1

Abstract

Early diagnosis is one of the important methods to  control tuberculosis because this disease is zoonotic which easily spread through the air. Early detection of tuberculosis in dog is also very important since dog as petanimal have a potency to transfer the disease to human or other animals. The discovery of two specific M.tuberculosisantigens, ESAT06 and CFP-10, provide the opportunity to developa specific diagnostic kit for tuberculosis by using ELISA based on the secretion of IFN-γ. The development of a tuberculosis diagnostic kit based on this molecular biology and immunological method would provide a good alternative method to detect tuberculosis specially, accurately as early as possible. The result of this experiment would provide contribution for the development of health science and technology, especially in the eradication of tuberculosis. Keywords: diagnosis, tuberculosis, ESAT-6, CFP-10, interferon-gamma.
Immunopathogenesis of severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection: a concise update Dewi, Shinta Trilaksmi; Soebono, Hardyanto
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 52, No 3 (2020)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1310.314 KB) | DOI: 10.19106/JMedSci005203202009

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which has been identified as the cause of the recently emerging coronavirus disease 2019 (COVID-19), a respiratory-related infectious disease, in late 2019. As of May 2020, SARS-CoV-2 has infected millions of people with almost 300.000 deaths worldwide only within few months since its first case was reported. While this infection mostly results in mild diseases, the increasing number of severe cases and deaths cannot be overlooked. Due to its novelty, many facets of SARS-CoV-2 pathogenesis are not well understood. This review presents updated knowledge on the key virus characteristics of SARS-CoV-2 and critical notes in the pathogenesis of this viral infection in human that is currently proposed to largely involve various aspects of the host immune responses. While the immediate impact of viral infection in the target cells contributes to the development of the disease, the ability of the virus to modify the host responses may result in the dysregulation of innate and adaptive immune responses, which commonly manifest in the severe spectrum of the disease. Having deep understanding on this complex process is central for tailoring appropriate management for the infected patients as well as for developing effective preventive measures, most importantly vaccine, which is hoped to occur in the near future.
Immune Dysregulation in Childhood Leprosy Flora Ramona Sigit Prakoeswa; Budi Prasetyo; Santi Martini; Hardyanto Soebono; Muhammad Yulianto Listiawan; Anang Endaryanto; Cita Rosita Sigit Prakoeswa
Indian Journal of Forensic Medicine & Toxicology Vol. 15 No. 2 (2021): Indian Journal of Forensic Medicine & Toxicology
Publisher : Institute of Medico-legal Publications Pvt Ltd

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37506/ijfmt.v15i2.14725

Abstract

Leprosy is a chronic infection which is caused by Mycobacterium leprae. Leprosy has long been considereda complex disease, in which host and environmental characteristics are as important as the pathogen todetermine disease outcome. Leprosy is an excellent model for examining the immunoregulatory functions.Children are believed to be the most vulnerable group to leprosy infection due to their immature immunity.This review is aimed to summarize the findings of previous studies about immune dysregulation in childhoodleprosy. This study highlighted the plausible maternal-fetal connection which are related in immunedysregulation in childhood leprosy.
Environmental Factors and Leprosy in Mother and Child: A Study in Endemic Areas in East Java, Indonesia Flora Ramona Sigit Prakoeswa; Hardyanto Soebono; Dominicus Husada; Hari Basuki Notobroto; Muhammad Yulianto Listiawan; Anang Endaryanto; Cita Rosita Sigit Prakoeswa
Indian Journal of Forensic Medicine & Toxicology Vol. 15 No. 2 (2021): Indian Journal of Forensic Medicine & Toxicology
Publisher : Institute of Medico-legal Publications Pvt Ltd

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37506/ijfmt.v15i2.14726

Abstract

Background: Leprosy is a chronic infection caused by Mycobacterium leprae. In endemic locations,children become vulnerable as a result of being continuously exposed to foci of active transmission from avery young age, especially from their mothers. This study aims to find association between environmentalrisk factors and leprosy in mothers and children in endemic areas.Methods: This study is a case-control study in endemic areas in Tuban Regency, East Java Province,Indonesia. Retrieval of data was done using structured questionnaire and direct measurement. Chi-squarewas used to assess the association between environmental factors and leprosy in mothers and children groups.Results: 22 pairs of cases and 57 pairs of controls were examined. It is found that access to clean wateris associated with leprosy in mothers in endemic areas (p value = 0.047, OR 3.080, CI 95% 2.232-4.251).Environmental factors are not associated with pediatric leprosy in endemic areas.Conclusion: The results of our study show that environmental factors are not associated with pediatricleprosy in endemic areas. Access to clean water is associated with leprosy in mothers in endemic areas.
Effect of Oxidative Stress on AhpC Activity and Virulence in katG Ser315 Thr Mycobacterium tuberculosis Mutant Ning Rintiswati; Tri Wibawa; Widya Asmara; Hardyanto Soebono
Indonesian Journal of Biotechnology Vol 16, No 2 (2011)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (287.371 KB) | DOI: 10.22146/ijbiotech.16369

Abstract

Mycobacterium tuberculosis strains resistance to INH is mainly caused by the alteration in several genesencoding the molecular targets. Mutation of katG at codon 315 especially Ser315Thr are responsible forINH resistance in a large proportion of TB cases. The aim of this study is to evaluate the influence of stressoxidative on AhpC activity of katG Ser315Thr of M.tuberculosis, and to find out the relation of AhpC and thevirulence of this mutant. The study design was laboratoric experimental, subjects of study were M.tuberculosisINH resistance strains, and the treatment were serial dose of H2O2. Eighty five M.tuberculosis INH resistantclinical strain were screened for mutation of katGSer315Thr by PCR/RFLP and characterized on the basis ofphenotypic properties (catalase activity and AhpC activity). AhpC activity of katG Ser315Thr M.tuberculosisstrains in response to oxidative stress condition was evaluated by culturing the strains on liquid culturemedium containing 1mM H2O2.To ascertain role of AhpC in the virulence of katGSer315Thr mutant strains, themutants were infected into human macrophages culture, and several indicator of virulence were observed (i.e:replication competence, and apoptosis induction on human macrophages). The results showed that katG Ser315Thr were identified in 23 (27,05%) of 85 INH resistance strains, all mutant strains had decrease of catalaseactivity. AhpC activity of katG Ser315Thr of M.tuberculosis increased significantly with increase of hydrogenperoxide dose. In addition , it has been shown that increased AhpC activity related to replication ability ofmutant, and reduction of apoptosis macrophages induction significantly. We conclude that the productionof AhpC of katG Ser315Thr M.tuberculosis induced by oxidative stress. There was a role of AhpC in virulenceof the M.tuberculosis katG Ser315Thr strains by replication capability and macrophages apoptosis.