Molecular diagnosis and source tracing of an infection of Aureobasidium pullulans

Aureobasidium pullulans (A. pullulans) is a dematiaceous, yeast-like fungus that is ubiquitous in nature, which can colonize the human hair and skin. A. pullulans has been clinically implicated to cause skin and soft tissue infections, meningitis, splenic abscesses, and peritonitis. Herein, molecular diagnostic of internal transcribed spacer (ITS) sequencing was used to investigate a suspected case of A. pullulans infection, and the infection source had been traced. A 27-year-old female case was suspected of kala-azar due to the recurrent fever. Bone marrow specimens were analyzed. The samples were negative for Leishmania, Penicillium marneffei and Histoplasma capsulatum. DNA was extracted from the bone marrow specimens, and the 583-bp sequence was amplified with the fungal ITS universal primers. The sequence was compared by Blast query to be identified as A. pullulans. A strain of A. pullulans was also isolated from the kitchen of the patient’s living room. Culture characteristics were the same as the human pathogens of A. pullulans, and the ITS sequence was identical to the bone marrow ITS amplification. In conclusion, a deep infection caused by A. pullulans is rare, often occurring in the indwelling catheter, which may cause peritonitis and other symptoms. ITS sequencing of fungi can be used as a diagnostic reference. As A. pullulans is a common fungus in environment, amplification of ITS sequence of A. pullulans in the aseptic body fluid would be necessary to make a comprehensive diagnosis based on the clinical symptoms and signs.

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The Increasing Impact of Translational Research in the Molecular Diagnostics of Neuromuscular Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22084274 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4274

Author(s):

Dèlia Yubero ◽

Daniel Natera-de Benito ◽

Jordi Pijuan ◽

Judith Armstrong ◽

Loreto Martorell ◽

...

Keyword(s):

Molecular Diagnosis ◽

Clinical Symptoms ◽

Neuromuscular Diseases ◽

Genomic Analysis ◽

Molecular Diagnostic ◽

Diagnostic Process ◽

Targeted Analysis ◽

Whole Exome ◽

Referral Hospitals ◽

Uncertain Significance

The diagnosis of neuromuscular diseases (NMDs) has been progressively evolving from the grouping of clinical symptoms and signs towards the molecular definition. Optimal clinical, biochemical, electrophysiological, electrophysiological, and histopathological characterization is very helpful to achieve molecular diagnosis, which is essential for establishing prognosis, treatment and genetic counselling. Currently, the genetic approach includes both the gene-targeted analysis in specific clinically recognizable diseases, as well as genomic analysis based on next-generation sequencing, analyzing either the clinical exome/genome or the whole exome or genome. However, as of today, there are still many patients in whom the causative genetic variant cannot be definitely established and variants of uncertain significance are often found. In this review, we address these drawbacks by incorporating two additional biological omics approaches into the molecular diagnostic process of NMDs. First, functional genomics by introducing experimental cell and molecular biology to analyze and validate the variant for its biological effect in an in-house translational diagnostic program, and second, incorporating a multi-omics approach including RNA-seq, metabolomics, and proteomics in the molecular diagnosis of neuromuscular disease. Both translational diagnostics programs and omics are being implemented as part of the diagnostic process in academic centers and referral hospitals and, therefore, an increase in the proportion of neuromuscular patients with a molecular diagnosis is expected. This improvement in the process and diagnostic performance of patients will allow solving aspects of their health problems in a precise way and will allow them and their families to take a step forward in their lives.

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Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.11.056 ◽

2019 ◽

Vol 109 ◽

pp. 1834-1840 ◽

Cited By ~ 25

Author(s):

Mohsen Ghoryani ◽

Zhaleh Shariati-Sarabi ◽

Jalil Tavakkol-Afshari ◽

Ali Ghasemi ◽

Javad Poursamimi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trial ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Clinical Symptoms ◽

Autologous Bone Marrow ◽

Refractory Rheumatoid Arthritis ◽

Autologous Bone

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A point-of-care diagnostic for differentiating Ebola from endemic febrile diseases

Science Translational Medicine ◽

10.1126/scitranslmed.aat0944 ◽

2018 ◽

Vol 10 (471) ◽

pp. eaat0944 ◽

Cited By ~ 19

Author(s):

David Sebba ◽

Alexander G. Lastovich ◽

Melody Kuroda ◽

Eric Fallows ◽

Joshua Johnson ◽

...

Keyword(s):

Ebola Virus ◽

Clinical Symptoms ◽

Point Of Care ◽

Hemorrhagic Fever ◽

Diagnostic Methods ◽

Outbreak Detection ◽

Molecular Diagnostic ◽

Clinical Samples ◽

Live Virus ◽

And Control

Hemorrhagic fever outbreaks such as Ebola are difficult to detect and control because of the lack of low-cost, easily deployable diagnostics and because initial clinical symptoms mimic other endemic diseases such as malaria. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need. Although rapid tests such as lateral flow can be broadly deployed, they are typically not well-suited for differentiating among multiple diseases presenting with similar symptoms. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect and differentiate infection with Ebola virus from other more common febrile diseases. Here, we developed and tested an immunoassay technology that uses surface-enhanced Raman scattering (SERS) tags to simultaneously detect antigens from Ebola, Lassa, and malaria within a single blood sample. Results are provided in <30 min for individual or batched samples. Using 190 clinical samples collected from the 2014 West African Ebola outbreak, along with 163 malaria positives and 233 negative controls, we demonstrated Ebola detection with 90.0% sensitivity and 97.9% specificity and malaria detection with 100.0% sensitivity and 99.6% specificity. These results, along with corresponding live virus and nonhuman primate testing of an Ebola, Lassa, and malaria 3-plex assay, indicate the potential of the SERS technology as an important tool for outbreak detection and clinical triage in low-resource settings.

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Rare incidence of non-secretory myeloma with talaromycosis: a case report

BMC Infectious Diseases ◽

10.1186/s12879-021-06641-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Haiting Qin ◽

Ye Qiu ◽

Yanmei Huang ◽

Mianluan Pan ◽

Dong Lan ◽

...

Keyword(s):

Computed Tomography ◽

Bone Marrow ◽

Differential Diagnosis ◽

Lymph Nodes ◽

Clinical Symptoms ◽

Subcutaneous Tissue ◽

Community Acquired Pneumonia ◽

Pathological Examination ◽

Subcutaneous Nodules ◽

Lung Lymph

Abstract Background Talaromyces marneffei (TM) primarily infects patients with co-morbidities that cause immunodeficiency, but non-secretory myeloma (NSMM) is rare. TSM and NSMM are associated with fever, osteolysis, and swollen lymph nodes, thereby making it difficult for clinicians to make differential diagnosis. In this case, we describe TM infection coexisting with NSMM. Case presentation We retrospectively reviewed the case of a male (without human immunodeficiency virus infection) with fever, thoracalgia, swollen lymph nodes, and subcutaneous nodules who presented to the First Affiliated Hospital of Guangxi Medical University in February 2014. Chest computed tomography revealed patchy infiltration and positron emission tomography/computed tomography showed increased metabolic activity in the lower-right lung, lymph nodes, left ninth rib, and right ilium. Pathological examination of the lung, lymph nodes, subcutaneous nodules, and bone marrow showed no malignancy, he was diagnosed with community-acquired pneumonia. His clinical symptoms did not improve after anti-bacterial, anti-Mycobacterium tuberculosis, and anti-non-M. tuberculosis treatment. Later, etiological culture and pathological examination of the subcutaneous nodule proved TM infection, and the patient was re-diagnosed with disseminated TSM, which involved the lungs, lymph nodes, skin, bone, and subcutaneous tissue. After antifungal treatment, the patient showed significant improvement, except for the pain in his bones. Imaging showed aggravated osteolysis, and bone marrow biopsy and immunohistochemistry indicated NSMM. Thus, we conclusively diagnosed the case as NSMM with TSM (involving the lungs, lymph nodes, skin, and subcutaneous tissue). His condition improved after chemotherapy, and he was symptom-free for 7 years. Conclusion TM infection is rare in individual with NSMM. Since they have clinical manifestation in common, easily causing misdiagnosis and missed diagnosis, multiple pathological examinations and tissue cultures are essential to provide a differential diagnosis.

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Indolent Neuroendocrine Tumor Involving the Bone Marrow

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-0488-intitb ◽

2003 ◽

Vol 127 (4) ◽

pp. 488-491

Author(s):

Ellen Schlette ◽

L. Jeffrey Medeiros ◽

Miloslav Beran ◽

Carlos E. Bueso-Ramos

Keyword(s):

Bone Marrow ◽

Neuroendocrine Tumor ◽

Bone Marrow Biopsy ◽

Clinical Symptoms ◽

Eosinophilic Cytoplasm ◽

Hydroxyindoleacetic Acid ◽

History Of ◽

Cardiac Valve Disease ◽

Immunohistochemical Studies

Abstract We report a unique case of a patient with a neuroendocrine tumor localized to the bone marrow. The patient had a history of hairy cell leukemia, and the neuroendocrine tumor was detected in a bone marrow biopsy specimen obtained to assess response to 2-chlorodeoxyadenosine therapy. The neuroendocrine tumor was present as nodules that replaced approximately 15% of the bone marrow medullary space and was composed of round cells with fine chromatin, indistinct nucleoli, and relatively abundant, granular, eosinophilic cytoplasm. Histochemical stains showed cytoplasmic reactivity with Grimelius and Fontana-Masson stains, and immunohistochemical studies showed positivity for keratin and chromogranin. The histologic, cytochemical, and immunohistochemical features resembled a carcinoid tumor, and metastasis to the bone marrow was considered initially. The patient was asymptomatic without diarrhea, flushing, or cardiac valve disease. Serotonin production, assessed by the measurement of serum 5-hydroxyindoleacetic acid and substance P levels, was normal. Extensive clinical and radiologic work-up and endoscopy of the gastrointestinal tract to detect a primary site other than the bone marrow were negative. Follow-up bone marrow biopsy 7 years after the initial diagnosis was positive for persistent neuroendocrine tumor. The patient has not received any therapy specific for the neuroendocrine tumor and has had no clinical symptoms or evidence of progression after 9 years of clinical follow-up. We suggest that this neuroendocrine tumor may have arisen in the bone marrow.

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Abstract 193: Hemophagocytic lymphohistiocytosis following kawasaki disease:Differential Diagnosis in IVIG Refractory Kawasaki Disease

Circulation ◽

10.1161/circ.131.suppl_2.193 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Hyun Ok Jun ◽

Eun Kyung Cho ◽

Jeong Jin Yu ◽

So Yeon Kang ◽

Chang Deok Seo ◽

...

Keyword(s):

Bone Marrow ◽

Coronary Artery ◽

Kawasaki Disease ◽

Skin Rash ◽

Hemophagocytic Lymphohistiocytosis ◽

Clinical Symptoms ◽

Early Recognition ◽

Cervical Lymphadenopathy ◽

Inflammatory Disorder ◽

Laboratory Findings

Introduction: Hemophagocytic lymphohistiocytosis(HLH) is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis and up-regulation of inflammatory cytokines. Thus, both HLH and Kawasaki disease(KD) are characterized by prolonged fever, and are diagnosed by a clinical and laboratory scoring system, concurrent manifestation of HLH and KD has been described in the literature. We describe two cases of children who diagnosed as KD initially, but after intravenous gamma globulin(IVIG) failed to produce clinical response, were found to have HLH. Case report: A 3-year-old boy who had previous KD history 5 months ago was admitted for 9day fever and skin rash. His symptoms were fulfilled KD criteria, and echocardiography showed dilated right coronary artery of 4.2mm. He was treated with 2 cycles of IVIG until fever subsided. However, 2 days later, he got fever again and cytopenia(Hb<9.0), hypertriglyceridemia, high level of ferritin was shown and had splenomegaly on physical examination. In the suspicion of HLH, bone marrow biopsy was done and revealed hemophagocytosis, consistent with HLH. A second case of 11-month-old boy admitted for 8-day fever with Kawasaki feature. Although, he showed incomplete feature(fever, skin rash, conjunctival injection, cervical lymphadenopathy), echocardiography showed dilated left main coronary artery(3.5mm) and treated with IVIG. However, 2days after IVIG administration, he was still pyrexial. The laboratory findings fulfilled 5 diagnostic criteria of HLH; bicytopenia(anemia, thrombocytopenia), hypofibrinogenemia, hyperferritinemia, hemophagocytosis in bone marrow, raised level of soluble IL-2 receptor. In both cases, the patients treated according to the HLH protocol 2004, and after that clinical symptoms and laboratory findings were improved. Several causes of febrile illness, EBV, CMV, rubella, parvo-viral infection, for example, were excluded. Comment: There is considerable overlap between the clinical syndromes of KD and HLH and early recognition and treatment of these two disease entity is imperative to avoid fatal outcomes in severe cases. Thus, these should both be considered and excluded in any child with unremitting fever and rash.

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Comparative Proteome-Wide Analysis of Bone Marrow Microenvironment of β-Thalassemia/Hemoglobin E

Proteomes ◽

10.3390/proteomes7010008 ◽

2019 ◽

Vol 7 (1) ◽

pp. 8 ◽

Cited By ~ 2

Author(s):

Saranyoo Ponnikorn ◽

Rungrawee Mongkolrob ◽

Suwit Klongthalay ◽

Sittiruk Roytrakul ◽

Kitima Srisanga ◽

...

Keyword(s):

Oxidative Stress ◽

Bone Marrow ◽

Clinical Symptoms ◽

Premature Death ◽

Ineffective Erythropoiesis ◽

Western Blot Assay ◽

Hemoglobin E ◽

Hb E ◽

Global Health Issue ◽

Alpha Globin

β-thalassemia/Hb E is a global health issue, which is characterized by a range of clinical symptoms from a mild and asymptomatic anemia to severe disorders that require transfusions from infancy. Pathological mechanisms of the disease involve the excess of unmatched alpha globin and iron overload, leading to ineffective erythropoiesis and ultimately to the premature death of erythroid precursors in bone marrow (BM) and peripheral organs. However, it is unclear as to how BM microenvironment factors contribute to the defective erythropoiesis in β-thalassemia/Hb E patients. Here, we employed mass spectrometry-based comparative proteomics to analyze BM plasma that was collected from six β-thalassemia/Hb E patients and four healthy donors. We identified that the differentially expressed proteins are enriched in secretory or exosome-associated proteins, many of which have putative functions in the oxidative stress response. Using Western blot assay, we confirmed that atypical lipoprotein, Apolipoprotein D (APOD), belonging to the Lipocalin transporter superfamily, was significantly decreased in BM plasma of the tested pediatric β-thalassemia/Hb E patients. Our results highlight that the disease condition of ineffective erythropoiesis and oxidative stress found in BM microenvironment of β-thalassemia/Hb E patients is associated with the impaired expression of APOD protein.

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Faulty ribosomes and human diseases: mistakes in “assembly line” going unnoticed ?

Journal of Health and Allied Sciences NU ◽

10.1055/s-0040-1703918 ◽

2015 ◽

Vol 05 (03) ◽

pp. 087-092

Author(s):

Anirban Chakraborty ◽

Indrani Karunasagar

Keyword(s):

Bone Marrow ◽

Assembly Line ◽

Clinical Symptoms ◽

Genetic Disorders ◽

Living Organism ◽

Cell Types ◽

Human Embryos ◽

Ribosome Assembly ◽

Specific Cell ◽

Specific Nature

AbstractRibosomes are molecular machineries that decode the information within mRNAs and generate all the proteins required for cellular activities. Ribosomes are essential to every living organism. The synthesis of ribosome is an intricate process, which is carried out in multiple steps throughout the cell in a highly coordinated fashion. For many years, the general perception was that any defects in the “ribosome assembly line” would have fatal consequences on cell. However, it has now become clear that production of defective ribosomes does not lead to lethality in human embryos. Rather, it manifests as specific disease conditions called ribosomopathies, which are rare genetic disorders affecting the bone marrow. This group of diseases has received considerable attention in recent years because of the mystery associated with them i.e. the tissue-specific nature of the clinical phenotypes despite the fact that the genes mutated in patients code for proteins that are absolutely essential and are housekeeping in nature. Despite considerable progress in understanding these diseases, it still remains unclear why defects in the production of a macromolecule as indispensable and as ubiquitous as the ribosome go unnoticed and why the effects are not universal but rather are restricted to specific cell types. This review is aimed at introducing the readers to important ribosomopathies with a brief description about the clinical symptoms, molecular genetics, and the treatments strategies.

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A man with recurrent fever, arthritis, and rashes-brucellosis? A case report

BMC Infectious Diseases ◽

10.1186/s12879-019-4746-0 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Wen Wang ◽

Xu Lu ◽

Chengbo Li ◽

Myong Jun Ri ◽

Wei Cui

Keyword(s):

Infectious Disease ◽

Bone Marrow ◽

Case Report ◽

Myelodysplastic Syndrome ◽

Skin Biopsy ◽

Rare Case ◽

Glucocorticoid Therapy ◽

Recurrent Fever ◽

Neutrophilic Dermatosis ◽

Case Presentation

Abstract Background We report a rare case of chronic brucellosis accompanied with myelodysplastic syndrome and neutrophilic dermatosis, which to the best of our knowledge, has never been reported. Case presentation A young man was admitted to our hospital complaining of recurrent fever, arthritis, rashes and anemia. He had been diagnosed with brucellosis 6 years prior and treated with multiple courses of antibiotics. He was diagnosed with myelodysplastic syndrome and neutrophilic dermatosis following bone marrow puncture and skin biopsy. After anti-brucellosis treatment and glucocorticoid therapy, the symptoms improved. Conclusions Clinicians should consider noninfectious diseases when a patient who has been diagnosed with an infectious disease exhibits changing symptoms.

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