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1.
Article in Chinese | WPRIM | ID: wpr-879560

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic basis for a pair of twins affected with hyaline fibromatosis syndrome (HFS).@*METHODS@#Clinical data of the twins were retrospectively analyzed. High-throughput sequencing was carried out to detect potential pathogenic variants. CLUSTALX was employed to analyze cross-species conservation of the mutant amino acids. Impact of the mutations was predicted by using software including PolyPhen-2 and Mutation taster.@*RESULTS@#The pair of twins have featured growth and intelligence retardation, and were found to carry compound heterozygous variants of the ANTXR2 gene including c.1214G>A and c.1074delT, among which c.1214G>A was unreported previously. Both variants were predicted to be pathogenic. In addition to growth and mental delay, the pair of twins also featured hyperplasia of the gum and soft tissue-like masses of the auricle. The younger brother had rupture of the auricle mass during follow-up.@*CONCLUSION@#The patients' condition can probably be attributed to the compound heterozygous variants of the ANTXR2 gene. Above finding has facilitated molecular diagnosis of the patients.


Subject(s)
Asian Continental Ancestry Group/genetics , China , Humans , Hyalinosis, Systemic/genetics , Male , Mutation , Pedigree , Receptors, Peptide/genetics , Retrospective Studies
2.
Article in English | WPRIM | ID: wpr-742359

ABSTRACT

PURPOSE: This study investigated the role of natriuretic peptide receptor 2 (NPR2) on cell proliferation and testosterone secretion in mouse Leydig cells. MATERIALS AND METHODS: Mouse testis of different postnatal stages was isolated to detect the expression C-type natriuretic peptide (CNP) and its receptor NPR2 by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Leydig cells isolated from mouse testis were cultured and treated with shNPR2 lentiviruses or CNP. And then the cyclic guanosine monophosphate production, testosterone secretion, cell proliferation, cell cycle and cell apoptosis in mouse Leydig cells were analyzed by ELISA, RT-qPCR, Cell Counting Kit-8, and flow cytometry. Moreover, the expression of NPR2, cell cycle, apoptosis proliferation and cell cycle related gene were detected by RT-qPCR and Western blot. RESULTS: Knockdown of NPR2 by RNAi resulted in S phase cell cycle arrest, cell apoptosis, and decreased testosterone secretion in mouse Leydig cells. CONCLUSIONS: Our study provides more evidences to better understand the function of CNP/NPR2 pathway in male reproduction, which may help us to treat male infertility.


Subject(s)
Animals , Apoptosis , Blotting, Western , Cell Count , Cell Cycle , Cell Cycle Checkpoints , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Germ Cells , Guanosine Monophosphate , Humans , Infertility, Male , Lentivirus , Leydig Cells , Male , Mice , Natriuretic Peptide, C-Type , Polymerase Chain Reaction , Receptors, Peptide , Reproduction , Reverse Transcription , RNA Interference , S Phase , Testicular Diseases , Testis , Testosterone
3.
Article in Korean | WPRIM | ID: wpr-742151

ABSTRACT

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms arising from the pancreatic islet of Langerhans and can be functioning or non-functioning based on the clinical symptoms caused by hormonal secretions. PNETs are the second most common tumor of the pancreas and represent 1–2% of all pancreatic neoplasms. The incidence of pNETs appears to be rising and the prognosis seems to be improving, likely due to the improved treatment options. Recent updates of the World Health Organization classification and grading separate pNETs into 2 broad categories according to the histopathologic criteria, including the Ki-67 proliferative index and mitotic counts: well-differentiated NET and poorly-differentiated neuroendocrine carcinoma (NEC). The classification also incorporates a new subcategory of well-differentiated high-grade NEC (grade 3) to the well-differentiated NET category. This new classification algorithm aims to improve the prediction of the clinical outcomes and survival and help clinicians select better therapeutic strategies for patient care and management. The treatment of advanced or metastatic pNETs may include surgical resection, liver-directed therapies, and/or systemic treatments. In unresectable patients, the goals of these therapies are to palliate the tumor-related symptoms and prolong the lifespan. Systemic therapy consists of the following broad modalities: somatostatin analogues, molecular targeted therapy, systemic chemotherapy, and peptide receptor radionuclide therapy. In conclusion, pNETs are diagnosed increasingly throughout the world, usually with metastatic disease and requiring systemic therapy. Each patient should be evaluated thoroughly and discussed individually by a multidisciplinary and dedicated NET-expert team, which might consider all treatment options, including ongoing clinical trials before selecting the appropriate treatment sequence.


Subject(s)
Carcinoma, Neuroendocrine , Classification , Drug Therapy , Humans , Incidence , Islets of Langerhans , Molecular Targeted Therapy , Neuroectodermal Tumors, Primitive , Neuroendocrine Tumors , Pancreas , Pancreatic Neoplasms , Patient Care , Prognosis , Receptors, Peptide , Somatostatin , World Health Organization
4.
Article in English | WPRIM | ID: wpr-786469

ABSTRACT

Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life.We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on ⁶⁸Ga-DOTATATE PET/CT and ¹¹¹In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient.Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or ¹⁸F-FDG PET/CT SUV(max) values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit.


Subject(s)
Counseling , Disease Progression , Humans , Liver , Neuroendocrine Tumors , Paraganglioma , Positron Emission Tomography Computed Tomography , Receptors, Peptide , Risk Factors , Tomography, Emission-Computed, Single-Photon
5.
Article in English | WPRIM | ID: wpr-786463

ABSTRACT

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.


Subject(s)
Hope , Humans , Lutetium , Membranes , Nuclear Medicine , Prostate , Radium , Receptors, Peptide , Singapore , Theranostic Nanomedicine , Yttrium
6.
Article in English | WPRIM | ID: wpr-786454

ABSTRACT

Exploring the unknown is one of the key factors that lead to great discoveries in mankind history.With the advances in medicine and the development of new approaches towards patient care, like next-generation sequencing and patient-centered care, the need for treatments tailored to patient through personalized medicine has become more compelling. Theranostics has been introduced as a combination of a diagnostic tool and a therapeutic tool on the same vector for a specific disease, to facilitate personalized medicine. Nuclear medicine has shown the capability of providing a strong platform for this new approach through its arms, molecular imaging, and targeted molecular therapies. Though the prototype of theranostics has been practiced in Jordan since decades in the field of diagnosis and treatment of well-differentiated thyroid cancer, recently, the King Hussein Cancer Center (KHCC), a leading and comprehensive cancer center in Jordan and in the Middle East, has leaped forward to introduce the new approaches of theranostics through the nuclear medicine applications. This paper sheds the light on the most important aspects of this new theranostics practice in Jordan such as peptide receptor radionuclide therapy (PRRT) and prostate-specific membrane antigen (PSMA)–based theranostics.


Subject(s)
Arm , Diagnosis , Humans , Jordan , Membranes , Middle East , Molecular Imaging , Molecular Targeted Therapy , Nuclear Medicine , Patient Care , Patient-Centered Care , Precision Medicine , Receptors, Peptide , Theranostic Nanomedicine , Thyroid Neoplasms
7.
Article in English | WPRIM | ID: wpr-786451

ABSTRACT

Medical managements are becoming personalized while diseases are being understood at the molecular level. Nuclear medicine is one of the fields actively contributing to this development. In particular, theranostics, a combinatorial term for therapy and diagnostics, enables accurate imaging and subsequent targeted radionuclide treatment. Due to its high impact in healthcare, many countries have begun to offer Ga-68 PET/CTscans and Lu-177 therapies. The Philippines has followed suit through the initiative of this author and able support of the administration and staff of St. Luke's Medical Center. The Ga-68 DOTATATE and PSMA PET/CT scans became officially available in January 2018 while the first peptide receptor radionuclide therapy for neuroendocrine tumor and first PSMA radioligand therapy for prostate cancer occurred in May and June 2018, respectively. Amidst past, present, and future challenges, theranostics has emerged in the Philippines, offering hope to cancer patients in the country.


Subject(s)
Delivery of Health Care , Hope , Humans , Neuroendocrine Tumors , Nuclear Medicine , Philippines , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms , Receptors, Peptide , Theranostic Nanomedicine
8.
Article in English | WPRIM | ID: wpr-786992

ABSTRACT

PURPOSE AND METHODS: Patients with inoperable andmetastasized neuroendocrine tumors (NETs), particularly those with grades 1 and 2, usually receive treatment with somatostatin analogues (SSAs). Peptide receptor radionuclide therapy (PRRT) has gained momentum over the past two decades in patients who progress on SSAs. 177Lu-DOTATATE is currently the most widely used radiopeptide for PRRT. We reviewed the recent evidence on PRRT and the treatment of gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).RESULTS: ¹⁷⁷Lu-DOTATATE can be used as neoadjuvant treatment in patients with inoperable GEP-NETs, who might be candidate for surgery after treatment and as adjuvant therapy after surgical intervention. Combination treatments of PRRT with chemotherapy or targeted agents as well as combinations of radionuclides in patients with NETs have been explored over the last few years. The majority of patients with NETs experience partial response or have disease stabilization, a small percentage has complete response, while some 30% of patients, however, will have disease progression. The safety and efficacy of retreatment with extra cycles of PRRT as salvage therapy have been evaluated in small retrospective series.CONCLUSION: Overall, there is evidence that disease control and quality of life improve significantly after 117Lu PRRT therapy. Clinical trials on this therapy are scarce, and there is a need for further studies to establish proper management guidelines.


Subject(s)
Disease Progression , Drug Therapy , Humans , Lutetium , Neoadjuvant Therapy , Neuroendocrine Tumors , Nuclear Medicine , Quality of Life , Radioisotopes , Receptors, Peptide , Retreatment , Retrospective Studies , Salvage Therapy , Somatostatin , Theranostic Nanomedicine
9.
Article in English | WPRIM | ID: wpr-786990

ABSTRACT

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.


Subject(s)
Neuroendocrine Tumors , Quality of Life , Receptors, Peptide , Receptors, Somatostatin , Somatostatin
10.
Article in Chinese | WPRIM | ID: wpr-344158

ABSTRACT

<p><b>OBJECTIVE</b>To identify pathogenic mutations of ANTXR2 gene in a patient with juvenile hyaline fibromatosis.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral venous blood sample from the patient. All coding exons (exons 1-17) and splicing sites of the ANTXR2 gene were amplified with PCR. Potential mutations were detected with direct sequencing of the PCR products. 100 unrelated healthy subjects were used as the controls. CLUSTALX (1.81) was employed to analyze cross-species conservation of the mutant amino acid. Impact of the mutations was analyzed with software including SIFT, PolyPhen-2 and MutationTaster.</p><p><b>RESULTS</b>A compound heterozygous mutation c.1074delT/c.1153G>C, was identified, among which c.1153G>C has not been reported previously and was predicted to be probably damaging. Both mutations were not found among the 100 healthy controls.</p><p><b>CONCLUSION</b>The patient's condition may be attributed to the compound heterozygous mutations of c.1074delT and c.1153G>C of the ANTXR2 gene. Above results has facilitated molecular diagnosis for this patient.</p>


Subject(s)
Child, Preschool , Female , Heterozygote , Humans , Hyalinosis, Systemic , Diagnosis , Genetics , Mutation , Receptors, Peptide , Genetics
11.
Article in English | WPRIM | ID: wpr-224846

ABSTRACT

Numerous musculoskeletal disorders are caused by thickened ligament, tendon stiffness, or fibrosis of joint capsule. Relaxin, a peptide hormone, can exert collagenolytic effect on ligamentous and fibrotic tissues. We hypothesized that local injection of relaxin could be used to treat entrapment neuropathy and adhesive capsulitis. Because hormonal effect depends on the receptor of the hormone on the target cell, it is important to confirm the presence of such hormonal receptor at the target tissue before the hormone therapy is initiated. The aim of this study was to determine whether there were relaxin receptors in the ligament, tendon, and joint capsular tissues of rats and to identify the distribution of relaxin receptors in these tissues. Transverse carpal ligaments (TCLs), inguinal ligaments, anterior cruciate ligaments (ACLs), Achilles tendons, and shoulder joint capsules were obtained from male Wistar rats. Western blot analysis was used to identify relaxin receptor isoforms RXFP1 and RXFP2. The distribution of relaxin receptors was determined by immunohistochemical staining. The RXFP1 isoform was found in all tissues examined. The RXFP2 isoform was present in all tissues but the TCLs. Its expression in ACLs tissues was relatively weak compared to that in other tissues. Our results revealed that RXFP1 and RXFP2 were distributed in distinctly different patterns according to the type of tissue (vascular endothelial cells, fibroblast-like cells) they were identified.


Subject(s)
Animals , Blotting, Western , Gene Expression Regulation , Immunohistochemistry , Ligaments/metabolism , Male , Rats , Rats, Wistar , Receptors, G-Protein-Coupled/genetics , Receptors, Peptide/genetics , Shoulder Joint/metabolism , Tendons/metabolism
12.
Article in Korean | WPRIM | ID: wpr-125500

ABSTRACT

Pancreatic neuroendocrine tumors (pNETs) are diverse diseases with different prognosis. Among available various therapeutic options, curative resection should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs are used to control hormonal symptoms and also effective to inhibit the tumor progression in specific settings. The molecular targeted agents such as sunitinib and everolimus are efficacious treatments for metastatic WHO grade 1/2 pNETs. Chemotherapy is generally used in highly symptomatic and rapidly growing pNETs such as WHO grade 3. In addition, local ablative therapy should be considered in patients with hepatic predominant unresectable metastatic pNETs, and peptide receptor radionucleotide therapy, which is unavailable in Korea, could be considered after failure of initial medical therapy. The most important of all is a multidisciplinary approach to pNETs. This is essential to optimal management of pNETs regarding the diverse disease nature


Subject(s)
Drug Therapy , Everolimus , Humans , Korea , Neuroectodermal Tumors, Primitive , Neuroendocrine Tumors , Prognosis , Receptors, Peptide , Somatostatin
13.
Article in English | WPRIM | ID: wpr-289909

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations.</p><p><b>METHODS</b>PROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS.</p><p><b>RESULTS</b>Of these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients.</p><p><b>CONCLUSION</b>PROKR2 may be the susceptibility gene of PSIS.</p>


Subject(s)
Exons , Gastrointestinal Hormones , Genotype , Humans , Mutation , Neuropeptides , Pituitary Diseases , Receptors, G-Protein-Coupled , Receptors, Peptide
14.
Yonsei Medical Journal ; : 33-40, 2016.
Article in English | WPRIM | ID: wpr-199916

ABSTRACT

PURPOSE: This study aimed to investigate whether Mullerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.


Subject(s)
Anti-Mullerian Hormone/pharmacology , Apoptosis/drug effects , Calcitriol/pharmacology , Caspase 3/metabolism , Caspase 9/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Fragmentation/drug effects , Enzyme-Linked Immunosorbent Assay , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Growth Inhibitors/metabolism , Humans , Ovarian Neoplasms/drug therapy , Receptors, Peptide , Receptors, Transforming Growth Factor beta , Signal Transduction/drug effects
15.
Korean Journal of Medicine ; : 354-356, 2013.
Article in Korean | WPRIM | ID: wpr-142790

ABSTRACT

Neuroendocrine tumors (NETs) are rare. However, several data showed the incidence is increased in the past 30 years. NETs can be both functional and non-functional, and may be undetected for years without obvious signs or symptoms. NET are classified as G1 (carcinoid), G2, G3 (large cell or small cell type), mixed adenoneuroendocrine carcinoma (MANEC), hyperplastic and preneoplastic lesions according to WHO classification 2010. NETs are often advanced at the time of diagnosis and is a progressive disease. Outcomes in patients with locally inoperable or metastatic NETs are poor, survival is also associated with tumor grade. Diagnosing NETs is the systematic approach. History taking and physical examiantion are essential and biochemical markers are useful. Imaging studies, somatostatin-receptor scintigraphy (Octreoscan(TM)), CT scan, MRI and/or PET scan can be used. Somatostatin receptor analogues showed symptomatic, biochemical and disease control. Targeted agents such as everolimus and sunitinib also showed benefit for advanced pancreatic NETs. Other treatments including peptide receptor radionuclide therapy (PRRT), hepatic regional therapy for liver metastases (arterial embolization, chemoembolization), or ablative therapy can be used. Chemotherapy, such as streptozotocin, 5-fluorouracil, doxorubicin, dacarbazin, etoposide, cisplatin, temozolomide, capecitabine is another option for the treatment of NETs. In conclusion, NETs are no longer rare disease. If we raise the index of suspicion for NETs, we can detect these tumors as earlier as possible. Local treatment is unique option for cure in earlier stage. The treatment for patients with advanced NETs, symptom and disease control is important with multidisciplinary team approaches.


Subject(s)
Biomarkers , Cisplatin , Dacarbazine , Deoxycytidine , Doxorubicin , Etoposide , Fluorouracil , Humans , Incidence , Indoles , Liver , Magnetic Resonance Imaging , Neoplasm Metastasis , Neuroendocrine Tumors , Positron-Emission Tomography , Pyrroles , Rare Diseases , Receptors, Peptide , Receptors, Somatostatin , Sirolimus , Streptozocin , Capecitabine , Everolimus
16.
Korean Journal of Medicine ; : 354-356, 2013.
Article in Korean | WPRIM | ID: wpr-142787

ABSTRACT

Neuroendocrine tumors (NETs) are rare. However, several data showed the incidence is increased in the past 30 years. NETs can be both functional and non-functional, and may be undetected for years without obvious signs or symptoms. NET are classified as G1 (carcinoid), G2, G3 (large cell or small cell type), mixed adenoneuroendocrine carcinoma (MANEC), hyperplastic and preneoplastic lesions according to WHO classification 2010. NETs are often advanced at the time of diagnosis and is a progressive disease. Outcomes in patients with locally inoperable or metastatic NETs are poor, survival is also associated with tumor grade. Diagnosing NETs is the systematic approach. History taking and physical examiantion are essential and biochemical markers are useful. Imaging studies, somatostatin-receptor scintigraphy (Octreoscan(TM)), CT scan, MRI and/or PET scan can be used. Somatostatin receptor analogues showed symptomatic, biochemical and disease control. Targeted agents such as everolimus and sunitinib also showed benefit for advanced pancreatic NETs. Other treatments including peptide receptor radionuclide therapy (PRRT), hepatic regional therapy for liver metastases (arterial embolization, chemoembolization), or ablative therapy can be used. Chemotherapy, such as streptozotocin, 5-fluorouracil, doxorubicin, dacarbazin, etoposide, cisplatin, temozolomide, capecitabine is another option for the treatment of NETs. In conclusion, NETs are no longer rare disease. If we raise the index of suspicion for NETs, we can detect these tumors as earlier as possible. Local treatment is unique option for cure in earlier stage. The treatment for patients with advanced NETs, symptom and disease control is important with multidisciplinary team approaches.


Subject(s)
Biomarkers , Cisplatin , Dacarbazine , Deoxycytidine , Doxorubicin , Etoposide , Fluorouracil , Humans , Incidence , Indoles , Liver , Magnetic Resonance Imaging , Neoplasm Metastasis , Neuroendocrine Tumors , Positron-Emission Tomography , Pyrroles , Rare Diseases , Receptors, Peptide , Receptors, Somatostatin , Sirolimus , Streptozocin , Capecitabine , Everolimus
17.
Oman Medical Journal. 2013; 28 (1): 53-55
in English | IMEMR | ID: emr-146732

ABSTRACT

Infantile Systemic Hyalinosis [ISH] [OMIM 236490] is a rare, progressive and fatal autosomal recessive disorder characterized by multiple subcutaneous skin nodules, gingival hypertrophy, osteopenia, joint contractures, failure to thrive, diarrhea with protein losing enteropathy, and frequent infections. There is diffuse deposition of hyaline material in the skin, gastrointestinal tract, muscle and endocrine glands. It is caused by mutations in the ANTXR2 [also known as CMG2] gene, which encodes a transmembranous protein involved in endothelial development and basement membrane-extracellular matrix assembly. We describe a child with classical features of ISH presenting in infancy with severe chronic debilitating pain and progressive joint contractures. The diagnosis was confirmed by molecular DNA sequencing of ANTXR2 gene which revealed a novel homozygous mutation not previously reported; 79 bp deletion of the entire exon 11 [c867_945del, p.E289DfsX22]. Although this is the first reported case of ISH in Oman, we believe that the disease is under-diagnosed since children affected with this lethal disease pass away early in infancy prior to establishing a final diagnosis


Subject(s)
Humans , Female , Mutation , Genes, Recessive , Chromosome Disorders , Gingival Hypertrophy , Bone Diseases, Metabolic , Contracture , Failure to Thrive , Diarrhea , Protein-Losing Enteropathies , Receptors, Peptide
18.
Arq. bras. endocrinol. metab ; 56(8): 473-478, Nov. 2012. ilus, tab
Article in English | LILACS | ID: lil-660252

ABSTRACT

OBJECTIVE: To screen for mutations in AMH and AMHR2 genes in patients with persistent Müllerian duct syndrome (PMDS). PATIENTS AND METHOD: Genomic DNA of eight patients with PMDS was obtained from peripheral blood leukocytes. Directed sequencing of the coding regions and the exon-intron boundaries of AMH and AMHR2 were performed. RESULTS: The AMH mutations p.Arg95*, p.Arg123Trp, c.556-2A>G, and p.Arg502Leu were identified in five patients; and p.Gly323Ser and p.Arg407* in AMHR2 of two individuals. In silico analyses of the novel c.556-2A>G, p.Arg502Leu and p.Arg407* mutations predicted that they were harmful and were possible causes of the disease. CONCLUSION: A likely molecular etiology was found in the eight evaluated patients with PMDS. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p.Arg502Leu in AMH; and p.Gly323Ser in AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8.


OBJETIVO: Analisar os genes AMH e AMHR2 em indivíduos com síndrome de persistência dos ductos de Müller (SPDM). PACIENTES E MÉTODO: Amostras de DNA genômico de oito pacientes com SPDM foram obtidas de leucócitos de sangue periférico. Sequenciamento direto da região codificadora e das áreas intrônicas próximas aos éxons dos genes AMH e AMHR foi realizado. RESULTADOS: As mutações p.Arg95*, p.Arg123Trp, c.556-2A>G e p.Arg502Leu no gene AMH foram identificadas em cinco pacientes e as mutações p.Gly323Ser e p.Arg407* no gene AMHR2, em dois indivíduos. As análises in silico das mutações c.556-2A>G, p.Arg502Leu e p.Arg407*, não descritas anteriormente na literatura, previram que elas são deletérias e possivelmente a causa da doença. CONCLUSÃO: Uma provável etiologia molecular foi encontrada nos oito pacientes portadores de SPDM avaliados. No gene do AMH foram identificadas quatro mutações e no AMHR2, duas mutações. Três das seis mutações encontradas são mutações novas, c.556-2A>G e p.Arg502Leu no gene AMH; e p.Gly323Ser no AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Male , Young Adult , /genetics , Anti-Mullerian Hormone/genetics , Receptors, Peptide/genetics , Receptors, Transforming Growth Factor beta/genetics , /blood , Anti-Mullerian Hormone/blood , DNA Mutational Analysis , Polymerase Chain Reaction , Receptors, Peptide/blood , Receptors, Transforming Growth Factor beta/blood
19.
The Ewha Medical Journal ; : 95-101, 2012.
Article in English | WPRIM | ID: wpr-211925

ABSTRACT

OBJECTIVES: There are 3 subtypes of natriuretic peptide (NP) receptors: type A natriuretic peptide receptor (NPRA), NPRB, and NPRC. The NPRA gene polymorphism, consisting of substition of methionine (ATG) to isoleucine (ATC) at nucleotide 1023 (M341I) of exon 3 was revealed to be associated with increased risk for essential hypertension (EH) in Japanese people. The purpose of this study is to investigate association between EH and the M341I polymorphism in the NPRA gene in Korea. METHODS: Eighty patients in whom type B natriuretic peptide (BNP) was measured were enrolled in this study. 66 patients had EH and 14 patients did not. The polymorphism of M341I was evaluated by multiplex genotyping polymerase chain reaction and by sequencing analysis. RESULTS: The overall distribution of alleles was not significantly different between the control and EH groups. However, the C/C homozygous genotype was found only in the EH group. In the EH group, patient carrying the C/C homozygous genotype had the trend of having higher systolic and diastolic BP levels regardless of the previous treatment, even though other laboratory markers including BNP levels had no significant differences according to the genotypes. CONCLUSION: This would be meaningful for the first identification of the M341I polymorphism in the NPRA gene and for the first suggestion of association of the EH with it in Korea.


Subject(s)
Alleles , Asian Continental Ancestry Group , Exons , Genotype , Humans , Hypertension , Isoleucine , Korea , Lifting , Methionine , Natriuretic Peptide, Brain , Polymerase Chain Reaction , Receptors, Peptide , Biomarkers
20.
Article in English | WPRIM | ID: wpr-235601

ABSTRACT

<p><b>OBJECTIVE</b>To break immune tolerance to prion (PrP) proteins using DNA vaccines.</p><p><b>METHODS</b>Four different human prion DNA vaccine candidates were constructed based on the pcDNA3.1 vector: PrP-WT expressing wild-type PrP, Ubiq-PrP expressing PrP fused to ubiquitin, PrP-LII expressing PrP fused to the lysosomal integral membrane protein type II lysosome-targeting signal, and PrP-ER expressing PrP locating the ER. Using a prime-boost strategy, three-doses of DNA vaccine were injected intramuscularly into Balb/c mice, followed by two doses of PrP protein. Two weeks after the last immunization, sera and spleens were collected and PrP-specific humoral and cellular immune responses evaluated by ELISA and ELISPOT tests.</p><p><b>RESULTS</b>Higher levels of serum PrP antibodies were detected in mice vaccinated using the strategy of DNA priming followed by protein boosting. Of these, WT-PrP, Ubiq-PrP, and PrP-LII induced significantly higher humoral responses. ELISPOT tests showed markedly increased numbers of IFN-γ-secreting T cells in mice vaccinated using the strategy of DNA priming followed by protein boosting after stimulation with recombinant PrP23-90 and PrP23-231. PrP-ER induced the strongest T-cell response.</p><p><b>CONCLUSION</b>Prion vaccines can break tolerance to PrP proteins and induce PrP-specific humoral and cellular immune responses.</p>


Subject(s)
Animals , Antibodies , Allergy and Immunology , CHO Cells , COS Cells , Chlorocebus aethiops , Cricetinae , Cricetulus , Enzyme-Linked Immunosorbent Assay , Female , HeLa Cells , Humans , Immune Tolerance , Interferon-gamma , Allergy and Immunology , Lysosomal-Associated Membrane Protein 2 , Genetics , Allergy and Immunology , Mice , Mice, Inbred BALB C , Peptide Fragments , Allergy and Immunology , Prions , Genetics , Allergy and Immunology , Receptors, Peptide , Genetics , Allergy and Immunology , Recombinant Fusion Proteins , Genetics , Allergy and Immunology , Recombinant Proteins , Allergy and Immunology , Transfection , Ubiquitin , Genetics , Allergy and Immunology , Vaccines, DNA
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