Intractable & Rare Diseases Research
Online ISSN : 2186-361X
Print ISSN : 2186-3644
Volume 6 , Issue 4
Showing 1-15 articles out of 15 articles from the selected issue
Reviews
  • Xiaodan Zheng, Yuhai Hu, Chengfang Yao
    2017 Volume 6 Issue 4 Pages 234-241
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 15, 2017
    JOURNALS FREE ACCESS

    Lung cancer remains one of the leading causes of death worldwide, and lung cancers have often already metastasized when diagnosed. Numerous studies have noted the infiltration of immune cells in the lung cancer microenvironment, but these cells play a dualistic role, i.e. they suppress and/or promote tumor development and growth based on tumor progression and different cytokines in the microenvironment. These tumor-infiltrating immune cells create different microenvironments depending on their type and interaction. Chemokines act as a bridge in this process by recruiting immune cells to the tumor site and they regulate the phenotypes and functions of those cells. The current review summarizes current knowledge about the tumor-infiltrating immune cells in lung cancer as well as the mechanisms involved in suppression and promotion of tumor development and growth.

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  • Zijuan Qi, Jing Luan, Xiaoyan Zhou, Yazhou Cui, Jinxiang Han
    2017 Volume 6 Issue 4 Pages 242-248
    Published: November 30, 2017
    Released: December 16, 2017
    JOURNALS FREE ACCESS

    Fibrodysplasia ossificans progressive (FOP) is an extremely rare autosomal dominant disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification that can induce a disabling second skeleton. Spontaneously occurring flare-ups can cause inflammatory soft tissue to swell, followed by progressive and disabling heterotopic endochondral ossification. FOP is very rare, with an estimated incidence of one case per two million individuals. There is no definitive treatment for FOP, but the longevity of patients with FOP can be extended by early diagnosis and appropriate prevention of flares-up. Some promising treatment strategies and targets have recently been reported. The current review describes the classical phenotype and genotype of FOP, useful methods of diagnosing the condition, therapeutic approaches and commonly used drugs, and experimental models used to study this disease.

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  • Jing Liu, Jing Luan, Xiaoyan Zhou, Yazhou Cui, Jinxiang Han
    2017 Volume 6 Issue 4 Pages 249-255
    Published: November 30, 2017
    Released: December 16, 2017
    JOURNALS FREE ACCESS

    Wilson's disease (WD) is an autosomal recessive disease caused by a mutation of the ATP7B gene, resulting in abnormal copper metabolism. The major clinical features of WD include liver disease, neurological disorders, K-F rings, and osteoporosis. The prevalence of WD in China is higher than that in Western countries. Early diagnosis and lifelong treatment will lead to better outcomes. Drugs such as sodium dimercaptosuccinate (Na-DMPS), Zn, and Gandou Decoction can be used to treat WD. Some studies have shown that the combination of traditional Chinese medicine and Western medicine is the best approach to treating WD. In order to identify better treatments, this article describes the specific clinical symptoms of Wilson's disease, its diagnosis, and treatment options.

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  • Junren Lu, Jing Han, Chi Zhang, Yi Yang, Zhenjun Yao
    2017 Volume 6 Issue 4 Pages 256-261
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: October 24, 2017
    JOURNALS FREE ACCESS

    Periprosthetic joint infection (PJI) is one of the most devastating postoperative complications of total knee arthroplasty (TKA). Treatment varies depending on the type of infection, but two-stage revision arthroplasty using an antibiotic spacer is considered to be the gold standard of treatment. Several types of spacers are available at the moment, each with different benefits and indications, and these spacers may be improved in the future. The primary goals of selecting a given spacer are to locally deliver antibiotics and to preserve soft tissue. Use of an appropriate spacer subsequently decreases the difficulty of the second revision, the operating time, and ultimately the risk of postoperative complications.

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Original Articles
  • Jun-ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Youhei Tosaki, Kenji ...
    2017 Volume 6 Issue 4 Pages 262-268
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 21, 2017
    JOURNALS FREE ACCESS

    Nasu-Hakola disease (NHD) is a rare autosomal recessive leukoencephalopathy caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2 expressed in microglia. A rare variant of the TREM2 gene encoding p.Arg47His causes a 3-fold increase in the risk for late-onset Alzheimer's disease (LOAD). A recent study demonstrated that a rare coding variant p.Ser209Phe in the ABI family member 3 (ABI3) gene, a regulator of actin cytoskeleton organization, confers risk of developing of LOAD, although the pattern of ABI3 expression in AD and NHD brains with relevance to microglial pathology remains to be characterized. We investigated the cell type-specific expression of ABI3 in the brains derived from four non-neurological controls (NC), ten AD and five NHD cases by immunohistochemistry. We identified an intense ABI3 immunoreactivity chiefly on a subset of microglia with ramified or amoeboid morphology located in the grey matter and the white matter of the frontal cortex and the hippocampus of NC, AD, and NHD cases. The immunolabeled area of ABI3-positive microglia was not significantly different among NC, AD, and NHD cases due to great variability from case to case. The clusters of ABI3-immunoreactive microglia were found exclusively in AD brains and they were associated with amyloid plaques. Although these observations do not actively support the view that ABI3-immunoreactive microglia play a central role in the development of leukoencephalopathy in NHD brains and the neurodegeneration in AD brains, the intense expression of ABI3 on microglia might regulate their migration under conditions of health and disease in the central nervous system (CNS).

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  • Zhiwei Zheng, Lin Wang, Jihong Pan
    2017 Volume 6 Issue 4 Pages 269-273
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 02, 2017
    JOURNALS FREE ACCESS

    Interferon stimulated gene 20-kDa (ISG20) has been implicated in the pathology of osteoarthritis (OA) and it has been separately found to be responsive to estrogen stimulation. OA disproportionately affects women, and especially older women, suggesting some role of reproductive hormones in its pathology. The current study characterized the expression of ISG20 following stimulation with estradiol (E2) and proinflammatory cytokines in OA synovial fibroblasts (OASFs). E2 and the proinflammatory cytokines interleukin-6 (IL-6), lipopolysaccharide (LPS), and tumor necrosis factor α (TNF-α) were used to stimulate OASFs in vitro. The expression of ISG20 before and after stimulation was detected using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting. E2 and proinflammatory cytokine (IL-6, LPS and TNF-α) stimulation significantly induced the expression of ISG20 both at the messenger RNA (mRNA) and protein level. Moreover, the induction was time- and dose-dependent. Small interfering RNA (siRNA) was transfected into OASFs, and expression of the inflammatory factors interleukin-1α (IL-1α), IL-6, and interleukin-10 (IL-10) was detected using RT-qPCR. Silencing ISG20 with siRNA inhibited the expression of IL-1α, IL-6, and IL-10. Thus, expression of ISG20 was regulated by estradiol and proinflammatory factors, while ISG20 in turn regulated the expression of other inflammatory factors. These data support the contention that ISG20 plays a role in the inflammatory process of OA.

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  • Yanqin Lu, Qingli Zuo, Yao Zhang, Yanzhou Wang, Tianyou Li, Jinxiang H ...
    2017 Volume 6 Issue 4 Pages 274-280
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 14, 2017
    JOURNALS FREE ACCESS

    The interferon-inducible transmembrane proteins (IFITMs) are a family of small transmembrane proteins belonging to the interferon (IFN)-stimulated gene (ISG) superfamily and strongly induced by IFNs. In this paper, we studied the expression profile of IFITMs in 32 organ tissues. The IFITM mRNA expression profile showed that IFITM1, IFITM2 and IFITM3 were expressed in each tissue, especially, in spermatophore, spermaduct, testicle and epididymis. The expression of IFITM1, IFITM2 and IFITM3 showed a trend from high to low. Except for IFITM3 and IFITM6, the others IFITMs were highly expressed in the bone marrow, and the expression level of them was higher in the tibia than that in other parts of the long bones. In liver, the relative expression of IFITM1 and IFITM3 was higher than that of other members. The expression level of IFITM5 was the highest in bone marrow, successively in pancreas, and it was low in skin, smooth muscle and fat. Interestingly, the expression profile of IFITM2 and IFITM7 in tissues was similar to IFITM5. The expression of IFITM2, IFITM5 and IFITM10 were higher in smooth muscle than that in skeletal muscle. IFITM2, IFITM5, IFITM7 and IFITM10 were both highly expressed in esophagus and trachea. In addition, the expression of IFITM6 in eyes was high, and also in pancreas, gallbladder and bone. In the present study, we systematically analyzed the mRNA expression profile of IFITMs in 32 organ tissues, providing the foundation for the study of the function of the IFITMs.

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  • Feifei Wang, Jing Chen, Zhewen Zhang, Juan Yi, Minmin Yuan, Mingyan Wa ...
    2017 Volume 6 Issue 4 Pages 281-290
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 14, 2017
    JOURNALS FREE ACCESS

    Patients with acute myeloid leukemia (AML) often have a poor prognosis due to drug resistance, which is regarded as a tough problem during the period of clinical therapeutics. It has been reported that autophagy, an important event in various cellular processes, plays a crucial role in mediating drug-resistance to cancer cells. Our study attempts to comparatively investigate the differences of basic and induced autophagic activity between drug-sensitive and multidrug-resistant AML cells. The level of basic autophagy in K562/ADM cells was higher than that in K562 cells, which could be characterized by more cytosolic contents-packaged autophagic vacuoles in K562/ADM cells when compared to that in K562 cells. The observation of MDC staining showed that the fluorescent intensity of autophagosomes in K562/ADM cells was stronger than that in K562 cells. The expression of Beclin1 and the ratio of LC3-II to LC3-I were distinctly higher in K562/ADM cells, however, P62 protein was relatively lower in K562/ADM cells. Furthermore, we found that nutrient depletion could induce autophagic activity of both cell lines. However, autophagic activity of K562/ADM cells was always maintained at a higher level in contrast with K562 cells. ADM (Adriamycin) was also capable of inducing autophagic activity of K562 and K562/ADM cells, but the autophagic alteration in K562 cells appeared earlier. Taken together, our findings suggest that autophagy exerts an important effect on formation and maintenance of drug-resistance in AML cells.

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Brief Reports
  • Alexander Marco Kollikowski, Florian Kahles, Svetlana Kintsler, Sandra ...
    2017 Volume 6 Issue 4 Pages 291-294
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 27, 2017
    JOURNALS FREE ACCESS

    Cardiac transthyretin-related (ATTR) amyloidosis is a severe cardiomyopathy for which therapeutic approaches are currently under development. Because non-invasive imaging techniques such as cardiac magnetic resonance imaging and echocardiography are non-specific, the diagnosis of ATTR amyloidosis is still based on myocardial biopsy. Thus, diagnosis of ATTR amyloidosis is difficult in patients refusing myocardial biopsy. Furthermore, myocardial biopsy does not allow 3D-mapping and quantification of myocardial ATTR amyloid. In this report we describe a 99mTc-DPD-based molecular imaging technique for non-invasive single-step diagnosis, three-dimensional mapping and semiquantification of cardiac ATTR amyloidosis in a patient with suspected amyloid heart disease who initially rejected myocardial biopsy. This report underlines the clinical value of SPECT-based nuclear medicine imaging to enable non-invasive diagnosis of cardiac ATTR amyloidosis, particularly in patients rejecting biopsy.

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  • Ambreen Asim, Sarita Agarwal, Inusha Panigrahi, Nazia Saiyed, Sonal Ba ...
    2017 Volume 6 Issue 4 Pages 295-298
    Published: November 30, 2017
    Released: December 16, 2017
    JOURNALS FREE ACCESS

    Altered global methylation levels revealed LINE-1 methylation in young mothers of Down syndrome (DS) compared to controls suggesting the possibility of impaired DNA methylation causing abnormal segregation of chromosome 21. Methylene Tetrahydrofolate Reductase (MTHFR) is one of the major enzymes of the folate metabolism pathway. MTHFR gene polymorphism has been associated with maternal risk for DS. Studies have revealed that increased MTHFR promoter methylation results in the reduction of MTHFR protein activity further leading to increased risk of various diseases. The aim of this study is to compare the levels of MTHFR promoter methylation in all three study groups. A total of 120 subjects were recruited for the study and was divided into the following three groups: Group I (mothers of DS without Congenital Heart Defects (CHD), n = 40); Group II (mothers of DS with CHD, n = 40); and Group III (age matched control mothers, n = 40). Genomic DNA was isolated from 2 ml peripheral blood and bisulfite treatment was done to convert all unmethylated cytosines into uracil followed by PCR amplification for MTHFR promoter region and Sanger's sequencing. Results showed that there was a two fold increase in methylated promoter region of MTHFR gene in group II compared to other groups. None of the methylation pattern was observed in the control group. MTHFR promoter methylation affects folate metabolism which is known to play a role in chromosomal breakage, abnormal chromosomal segregation and genomic instability and therefore a developmental defect in the form of congenital cardiac anomaly.

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  • Hongwen Zhang, Fang Wang, Xiaoyu Liu, Xuhui Zhong, Yong Yao, Huijie Xi ...
    2017 Volume 6 Issue 4 Pages 299-303
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 27, 2017
    JOURNALS FREE ACCESS

    Hereditary nephrotic syndrome often presents with steroid-resistance and onset within the first year of life. Mutations in genes highly expressed in podocytes have been found in two thirds of these patients, especially NPHS1 and NPHS2 among at least 29 genetic causes that have been discovered. We reported two siblings with steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at NPHS1 (c.1339G>A, p.E447K) and ACDK4 (c.748G>C, p.D250H) genes. The siblings presented with steroid-resistant nephrotic syndrome and pathological lesions of focal segmental glomerulosclerosis (FSGS), while the elder sister also developed hypertension, renal failure and cardiac dysfunction.

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Case Reports
  • Kyle D. Klingbeil, Alexandra Balaban, Raymond M. Fertig, A. Caresse Ga ...
    2017 Volume 6 Issue 4 Pages 304-309
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 15, 2017
    JOURNALS FREE ACCESS

    Inflammatory fibroid polyps (IFP) are an extremely rare entity that arise within the submucosa of the gastrointestinal tract, and represent less than 0.1% of all gastric polyps. They are most commonly localized to the gastric antrum, small intestines and recto-sigmoid colon. IFPs are most commonly found incidentally upon endoscopic evaluation in the absence of symptoms. Presenting symptoms depend on the location of the tumor, although polyps located in the stomach most commonly present with epigastric pain and early satiety. Classic histologic features include perivascular onion skinning of spindle cells with an abundance of eosinophilic infiltration. The prompt diagnosis and management of IFP is essential due to its underlying risk for intussusception, outlet obstruction and acute hemorrhage. In addition, recent evidence has shown that IFP is driven by an activating mutation in the platelet derived growth factor receptor alpha (PDGFRA) gene, suggesting a neoplastic etiology. Herein, we discuss a case of a 65-year-old woman with an inflammatory fibroid polyp of the gastric antrum who initially presented with early hypovolemic shock and melena. Diagnosis was made by endoscopic visualization, biopsy and immunohistochemical analysis.

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  • Ghazal Tansir, Neha Rastogi, Prashant Ramteke, Prabhat Kumar, Manish S ...
    2017 Volume 6 Issue 4 Pages 310-313
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 14, 2017
    JOURNALS FREE ACCESS

    A 15 year old girl presented with complaints of prolonged fever and recurrent episodes of hemoptysis. Initial investigation showed pancytopenia and radiological imaging was suggestive of necrotizing pneumonia. Subsequently, mucor was isolated from bronchoalveolar lavage fluid, but even on appropriate medications her condition kept deteriorating. She had multiple bouts of hemoptysis and a repeat imaging of chest showed dissemination of mucormycosis to pulmonary vein and heart. Bone marrow biopsy identified acute lymphoblastic leukemia (ALL) as the cause of pancytopenia. She was planned for bronchial artery embolization and chemotherapy for ALL, but consent was not given and she left our institute against medical advice. Our case highlights the importance of keeping a high index of suspicion for disseminated mucormycosis in neutropenic patients, as any delay in diagnosis and treatment could have grave consequences.

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  • Ghazal Tansir, Chhavi Gupta, Shubham Mehta, Prabhat Kumar, Manish Sone ...
    2017 Volume 6 Issue 4 Pages 314-318
    Published: November 30, 2017
    Released: December 16, 2017
    JOURNALS FREE ACCESS

    Dengue fever is endemic in the Indian subcontinent and can have myriad presentations. The term expanded dengue syndrome (EDS) is used for atypical manifestations in dengue fever. We present a rare case of EDS in a patient with secondary dengue infection who developed rhabdomyolysis induced acute kidney injury (RAKI) along with intracranial and intraorbital bleeds. Patient was successfully managed in our institute and was discharged in stable condition. To the best of our knowledge, this is the only reported case of simultaneous occurrence of these complications in a dengue patient. This case is being presented to make clinicians aware of the spectrum of dengue infection.

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Communication
  • Paolo Chieffi
    2017 Volume 6 Issue 4 Pages 319-321
    Published: November 30, 2017
    Released: December 16, 2017
    [Advance publication] Released: November 21, 2017
    JOURNALS FREE ACCESS

    Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. Clinically several types of immunohistochemical markers are useful and sensitive. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include OCT3/4, HMGA1 and 2, NANOG, SOX2, and LIN28. Gene expression in TGCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TGCT subtypes that reflect the normal developmental switch in primordial germ cells from an under to normally methylated genome.

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