scholarly journals PARK2 Patient Presenting with Dopa-Responsive Dystonia

2021 ◽  
pp. 749-754
Author(s):  
Fumihito Yoshii ◽  
Koji Aono ◽  
Ryuya Kumazawa ◽  
Wakoh Takahashi
Keyword(s):  
Cognitive Assessment ◽  
Autosomal Recessive ◽  
Specific Binding ◽  
Genetic Disorders ◽  
Japanese Version ◽  
Myocardial Scintigraphy ◽  
Continuous Treatment ◽  
Specific Binding Ratio ◽  
Heart To Mediastinum Ratio ◽  
History Of

We report a 34-year-old female PARK2 patient presenting with dopa-responsive dystonia (DRD). She noticed difficulty in raising her foot while walking at the age of 24. Her lower limb symptoms were identified as dystonia later, and she was started on Menesit, which resulted in improvement of her symptoms. She was diagnosed as DRD and has been on continuous treatment since then. The specific binding ratio (SBR) of <sup>123</sup>I FP-CIT SPECT was significantly lower than those of controls of the same age, but <sup>123</sup>I-meta-iodobenzylguanidine myocardial scintigraphy showed a normal heart to mediastinum ratio. The Montreal Cognitive Assessment, Japanese version, was normal for her age. DRD is an inherited dystonia that typically begins during childhood and may be caused by mutations of the GCH1 (GTP cyclohydrolase), SPR (sepiapterin reductase), or TH (tyrosine hydroxylase) genes. Our patient was diagnosed as PARK2, known as autosomal-recessive juvenile Parkinson’s disease, based on genetic analysis. Although there was no family history of the disease, the decrease in SBR of <sup>123</sup>I FP-CIT SPECT enabled us to diagnose PARK2 and to differentiate this from DRD due to other genetic disorders.

Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent

2018 ◽  
Vol 18 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Mohsen Mohammadgholi ◽  
Nourollah Sadeghzadeh ◽  
Mostafa Erfani ◽  
Saeid Abediankenari ◽  
Seyed Mohammad Abedi ◽  
...  
Keyword(s):  
Radioligand Binding ◽  
Specific Binding ◽  
Specific Protein ◽  
Tumour Imaging ◽  
Specific Binding Ratio ◽  
Tumour Uptake ◽  
Technetium 99M ◽  
In Vivo Experiments ◽  
Human Fibronectin

Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling. Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one. Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

scholarly journals Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability

2021 ◽  
Author(s):  
Thu Hang Lai ◽  
Magali Toussaint ◽  
Rodrigo Teodoro ◽  
Sladjana Dukić-Stefanović ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Specific Binding ◽  
Radiochemical Yield ◽  
Toxicity Study ◽  
In Vivo Evaluation ◽  
One Pot ◽  
Specific Binding Ratio ◽  
Mri Studies ◽  
The Brain

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

scholarly journals COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome

2021 ◽  
pp. 1-3
Author(s):  
Setareh Alabaf ◽  
Karen O'Connell ◽  
Sithara Ramdas ◽  
David Beeson ◽  
Jacqueline Palace
Keyword(s):  
High Risk ◽  
Neuromuscular Transmission ◽  
Genetic Disorders ◽  
Severe Disease ◽  
Congenital Myasthenic Syndrome ◽  
Referral Centre ◽  
History Of ◽  
Myasthenic Syndrome ◽  
The Uk ◽  
Rare Group

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

Long-Term Survival of a Patient with Hepatocellular Carcinoma under Treatment with Viscum album – Case Report

2021 ◽  
pp. 237-243
Author(s):  
Ana Catarina Viana Valle ◽  
Aloísio Cunha de Carvalho
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Liver Neoplasm ◽  
Viscum Album ◽  
Health Condition ◽  
Continuous Treatment ◽  
Term Survival ◽  
History Of ◽  
Application Frequency

Hepatocellular carcinoma (HCC) is the most common liver neoplasm in dogs and can be treated by the Viscum album therapy in a curative or palliative way. The objective is to report a hepatocellular carcinoma case in a dog treated by homeopathic therapy, extending to Palliative Care, with a 24-month survival. A 12-year-old Schnauzer male with a history of a liver nodule was treated by intravenous and subcutaneous applications of V. album in different dynamization and combinations, chromotherapy, and oral homeopathic medicines. The tumor growth was controlled, and the health condition of the patient was stable while the medication was given as prescribed. However, as application frequency was reduced, tumor growth increased, and health deterioration was verified. Nevertheless and contrary to expectations, the patient had a 24-month survival. Therefore, these findings point to the potential of V. album on enhancing the quality of life, controlling tumor growth, and prolonging survival on patients with HCC. Patients under continuous treatment would benefit better of these properties.

scholarly journals Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT analysis

2018 ◽  
Vol 33 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Mahmudur G. M. Rahman ◽  
Muhammad M. Islam ◽  
Tetsuya Tsujikawa ◽  
Yasushi Kiyono ◽  
Hidehiko Okazawa
Keyword(s):  
Specific Binding ◽  
Specific Binding Ratio ◽  
Binding Ratio ◽  
Ratio Calculation

scholarly journals Clinical and Immunological Features of Human BCL10 Deficiency

2021 ◽  
Author(s):  
Blanca Garcia Solis ◽  
Ana Van Den Rym ◽  
Jareb J. Pérez-Caraballo ◽  
Abdulwahab Al –Ayoubi ◽  
Lazaro Lorenzo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Respiratory Infections ◽  
Genetic Diagnosis ◽  
Additional Patient ◽  
Hematopoietic Stem ◽  
Recommended Treatment ◽  
History Of ◽  
Different Populations ◽  
Human Immune

Abstract The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients prevented gaining that knowledge for this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we describe in more depth an additional patient with autosomal recessive BCL10 complete deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the almost absence of memory B and T cells reported before, this patient display a reduction in NK, gdT, Tregs, and TFH cells. The patient suffered from recurrent respiratory infections since early in life, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cured this disease.

scholarly journals Molecular genetic verification of isolated mineralocorticoid deficiency due to aldosterone synthase deficiency

2009 ◽  
Vol 55 (1) ◽  
pp. 28-30
Author(s):  
N Yu Kalinchenko ◽  
N A Zubkova ◽  
A N Tyulpakov
Keyword(s):  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Adrenal Hyperplasia ◽  
Genetic Studies ◽  
Aldosterone Synthase ◽  
Salt Wasting ◽  
History Of ◽  
17 Hydroxyprogesterone ◽  
Aldosterone Synthase Deficiency

Isolated mineralocorticoid deficiency is a rare hereditary autosomal recessive disorder that is characterized by salt wasting and that has the severest manifestations in infants. This paper is the first in the Russian literature to describe cases of isolated aldosterone deficiency. In both cases, the patients were monitored and treated for misdiagnosed congenital adrenal hyperplasia; however, the permanently low level of 17-hydroxyprogesterone could put in doubt the diagnosis and suspect isolated mineralocorticoid deficiency, by keeping in mind a history of salt wasting. By using the presented cases as an example, the authors give an algorithm for the examination and differential diagnosis of this condition and other diseases that have the similar clinical picture. Aldosterone synthase deficiency in patients was verified by molecular genetic studies - there were mutations in the CYP112 gene.

scholarly journals The Use of Whole Genome and Exome Sequencing for Newborn Screening: Challenges and Opportunities for Population Health

2021 ◽  
Vol 9 ◽  
Author(s):  
Audrey C. Woerner ◽  
Renata C. Gallagher ◽  
Jerry Vockley ◽  
Aashish N. Adhikari
Keyword(s):  
Newborn Screening ◽  
Exome Sequencing ◽  
Genetic Disorders ◽  
Population Based ◽  
Lessons Learned ◽  
Screening Tests ◽  
Whole Genome ◽  
Whole Exome ◽  
Challenges And Opportunities ◽  
History Of

Newborn screening (NBS) is a population-based program with a goal of reducing the burden of disease for conditions with significant clinical impact on neonates. Screening tests were originally developed and implemented one at a time, but newer methods have allowed the use of multiplex technologies to expand additions more rapidly to standard panels. Recent improvements in next-generation sequencing are also evolving rapidly from first focusing on individual genes, then panels, and finally all genes as encompassed by whole exome and genome sequencing. The intersection of these two technologies brings the revolutionary possibility of identifying all genetic disorders in newborns, allowing implementation of therapies at the optimum time regardless of symptoms. This article reviews the history of newborn screening and early studies examining the use of whole genome and exome sequencing as a screening tool. Lessons learned from these studies are discussed, along with technical, ethical, and societal challenges to broad implementation.

scholarly journals GENE THERAPY FOR HAEMOPHILIA

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
A Asghar ◽  
Z Asjad ◽  
H Tahir ◽  
Z Maheen ◽  
S Hanif
Keyword(s):  
Gene Therapy ◽  
Gene Editing ◽  
Genetic Disorders ◽  
Coagulation Factor ◽  
Retroviral Vectors ◽  
Adeno Associated Virus ◽  
General Application ◽  
Blood Disorder ◽  
Statistical Consideration ◽  
History Of

The blood disorder, Hemophilia, has its roots embedded deep into the history of genetic disorders. The European royal family is one of the most prominent families to be affected by this disease thus, dubbing it 'the royal disease'. The types of Hemophilia are divided into two based on the type of coagulation factor mutation found in the patient. For treating haemophilia, gene therapy is done by using different vectors such as lentiviral and retroviral vectors but due to the production of limited expression different adeno associated virus (AAV) strains are used. Some engineerly modified vectors are currently used to get the best possible results. The clinical trials prove the efficacy of these vectors so through their obtained statistical consideration, patient experience and population study once can design vaccines and drugs for haemophilia patients but also due to pre-existing Nabs and pre-existing HCV or HBV infection, the general application of AAV gene therapy is currently limited. The possibility of gene editing for the repair of the mutation is on the horizon.

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