ABSTRACT
Parathyroid carcinoma (PC) is a rare disease accounting for approximately 1% of primary hyperparathyroidism cases. The preoperative differentiation of PC is critical because PC can occasionally metastasise and invade the local tissue. However, this is challenging in asymptomatic cases and when the tumour is adjacent to the thyroid. Herein, we report a rare case of PC without clinical symptoms. Fine needle aspiration was performed, despite being contraindicated in PC, and an intrathyroidal tumour was preoperatively suggested.
Subject(s)
Parathyroid Neoplasms , Biopsy, Fine-Needle , Humans , Parathyroid Neoplasms/diagnostic imaging , Parathyroid Neoplasms/surgery , Thyroid GlandABSTRACT
N-ethylmaleimide-sensitive factor (NSF) plays a critical role in intracellular vesicle transport, which is essential for neurotransmitter release. Herein, we, for the first time, document human monogenic disease phenotype of de novo pathogenic variants in NSF, that is, epileptic encephalopathy of early infantile onset. When expressed in the developing eye of Drosophila, the mutant NSF severely affected eye development, while the wild-type allele had no detectable effect under the same conditions. Our findings suggest that the two pathogenic variants exert a dominant negative effect. De novo heterozygous mutations in the NSF gene cause early infantile epileptic encephalopathy.
Subject(s)
N-Ethylmaleimide-Sensitive Proteins/genetics , Spasms, Infantile/genetics , Animals , Drosophila , Female , Humans , MutationABSTRACT
The patient was a 61-year-old woman with thyroid enlargement since her 20s. She began to fall down repeatedly towards the end of June 2015. She was admitted to our hospital in the middle of August because of difficulty in walking. Upon admission, she presented with neck tremor and was unable to maintain a sitting position due to ataxia of the trunk and limbs. We studied serum anti-neuronal antibodies and obtained a positive result for anti-amphiphysin antibody (AMPH-Ab). Cerebrospinal fluid analysis revealed elevated protein levels and IgG index. Other than the thyroid mass, a tumor was not detected. The resected thyroid specimen showed follicular adenoma. After performing immunotherapies, the cerebrospinal fluid protein levels and IgG index decreased, and her ataxia did not progress. When subacute cerebellar ataxia is suspected, studying AMPH-Ab should be considered.
Subject(s)
Adenocarcinoma, Follicular/complications , Autoantibodies/blood , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/etiology , Nerve Tissue Proteins/immunology , Paraneoplastic Syndromes, Nervous System/diagnosis , Paraneoplastic Syndromes, Nervous System/etiology , Thyroid Neoplasms/complications , Acute Disease , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Cerebellar Ataxia/therapy , Cerebrospinal Fluid Proteins/analysis , Female , Humans , Immunoglobulin G/cerebrospinal fluid , Immunotherapy , Middle Aged , Paraneoplastic Syndromes, Nervous System/therapyABSTRACT
We assessed the possibility of C57BL/6-Tg (Meg1/Grb10)isn(Meg1 Tg) mice as a non-obese type 2 diabetes (2DM) animal model. Meg1 Tg mice were born normal, but their weight did not increase as much as normal after weaning and showed about 85% of normal size at 20 weeks of age. Body mass index of Meg1 Tg mice was also smaller than that of control mice. The glucose tolerance test and insulin tolerance test showed that Meg1 Tg mice had reduced ability to normalize the blood glucose level. Blood urea nitrogen (BUN) in Meg1 Tg mice (19.6 +/- 1.2 mg/dl) was significantly lower than in controls (22.0 +/- 0.8 mg/dl), while plasma triglyceride, insulin, adiponectin, and resistin levels were significantly higher (202.0 +/- 23.4 mg/dl vs 146.3 +/- 23.4 mg/dl, 152.4 +/- 16.3 pg/ml vs 88.1 +/- 16.9 pg/ml, 74.4 +/- 10.9 microg/ml vs 48.3 +/- 7.0 microg/ml, and 4.0 +/- 0.2 ng/ml vs 3.6 +/- 0.2 ng/ml, respectively). Body, visceral fat weight and liver weights were significantly lower (19.6 +/- 0.4 g vs 24.3 +/- 0.3 g, 376.7 +/- 29.6 mg to 507.5 +/- 23.0 mg, and 906.0 +/- 41.8 mg to 1,001.0 +/- 15.1 mg, respectively). Thus, hyperinsulinemia observed in Meg1 Tg mice indicates that their insulin signaling pathway is somehow inhibited. With high fat diet, the diabetes onset rate of Meg1 Tg mice increased up to 60%. These results suggest that Meg1 Tg mice resemble human 2DM.
Subject(s)
Diabetes Mellitus, Type 2/veterinary , Disease Models, Animal , Mice, Transgenic , Adiponectin/blood , Animals , Blood Urea Nitrogen , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Dietary Fats , Glucose Tolerance Test , Insulin/blood , Insulin/pharmacology , Lipase/blood , Mice , Resistin/blood , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
The congenitally athymic nude rat is used for studying cancer and transplantation owing to its hairlessness and T-cell defective function caused by the Foxn1(rnu) gene. However, NK cell activity of the nude rat is markedly increased. It is known that NK cells play a major role in rejection of xenografts and in cytotoxicity against tumor cells. Thus, the athymic nude rat with impaired NK cell activity should be a useful model for extensive studies. The DA-Lyst(bg)/Lyst(bg) rat, a model for human Chediak-Higashi syndrome (CHS) is characterized by diluted-coat color and impairment of NK cell activity. We planned to establish a combined immunodeficient double mutant rat introgressed with the Foxn1(rnu) and Lyst(bg) genes and a set of congenic strains having an identical genetic backgrounds simultaneously. Based on the phenotypic and genetic characteristics of the parental rat strains, the new strains were produced using continuous backcross and diagnosis with molecular genetic techniques. Each disease gene was diagnosed with PCR-RFLP or the long-nested PCR method. Furthermore, we used a marker-assisted congenic strategy based on scanning the genetic backgrounds of the parental rats with 461 rat microsatellite markers. We think that the newly established DA/Slc-Foxn1(rnu)/Foxn1(rnu) Lyst(bg)/Lyst(bg) double mutant will be useful as a severe disease model for human CHS, and the set of DA/Slc-Foxn1(rnu) Lyst(bg) congenic strains which have impaired NK cell activity and/or defective T cell function should be useful for studying in cancer research, xenotransplantation, immune function and other wide-ranging studies.
Subject(s)
Animals, Congenic , DNA-Binding Proteins/genetics , Disease Models, Animal , Proteins/genetics , Rats, Mutant Strains , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/immunology , Transcription Factors/genetics , Animals , Chediak-Higashi Syndrome/genetics , Chediak-Higashi Syndrome/immunology , Forkhead Transcription Factors , Killer Cells, Natural/immunology , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Rats , T-Lymphocytes/immunologyABSTRACT
Two spontaneous mutant beige rats, with phenotypes resembling human Chediak- Higashi syndrome (CHS), were found independently in two inbred strains. Both beige mutations were identified to be recessive alleles in the Lyst locus on rat chromosome 17 and the alleles were denoted Lyst(bg) and Lyst(bg-Kyo). As it is almost impossible to discriminate these mutations phenotypically, we developed an allele-specific genotyping method for the Lyst gene. The nested PCR amplification was followed by restriction fragment length polymorphism (RFLP) analysis. By this method, we could discriminate the mutant Lyst(bg), Lyst(bg-Kyo) alleles, and the normal Lyst allele, easily and accurately.
Subject(s)
Alleles , Animals , Base Sequence , DNA Primers , Electrophoresis , Genes, Recessive/genetics , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , RatsABSTRACT
Changes in norepinephrine-induced transient contractions in Ca2+-deficient solution were investigated in the aortic smooth muscles of diabetic ALS (alloxan-induced diabetes susceptible) mice. The transient contractions in diabetic mice were significantly larger than those in normal mice. The longer incubation of the muscle preparations in Ca2+-deficient solution made the transient contractions smaller, probably due to the leakage and decrease in norepinephrine-releasable stored Ca2+. The rate of this reduction in contraction was slower in diabetic mice. These results suggest that the leakage of intracellular stored Ca2+ caused by extracellular Ca2+ deficiency is attenuated in diabetic mice, contributing to enhanced norepinephrine-induced transient contractions.
Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/physiology , Norepinephrine/pharmacology , Animals , Aorta/drug effects , MiceABSTRACT
A new polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was developed for genetic typing of the mouse Tnfsf6gld mutation. An artificial restriction site was introduced to the mouse Tnfsf6gld mutation by PCR amplification using a modified primer. The three genotypes of the Tnfsf6 locus (Tnfsf6gld/Tnfsf6gld, Tnfsf6gld/+, and +Tnfsf6-gld/+Tnfsf6-gld) could be distinguished clearly and easily. This PCR-RFLP analysis was found to be useful for the identification of the mouse Tnfsf6gld mutation.
Subject(s)
Mice, Inbred C3H/genetics , Point Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Tumor Necrosis Factor-alpha/genetics , Animals , Chromosome Mapping , DNA Mutational Analysis/methods , DNA Primers , Genotype , MiceABSTRACT
To determine the effects of high temperature on the number of alveolar macrophages (AMs) in bronchoalveolar lavage (BAL) fluid in rats, F344 rats were housed in environment chambers at 23 degrees C, 30 degrees C or 35 degrees C for up to 14 days. The number of AMs in the BAL fluid was significantly decreased in rats housed at 35 degrees C on days 7 and 14, compared to the control group housed at 23 degrees C. The total protein content and lactate dehydrogenase activity did not change at high temperatures in BAL supernatant, indicating that there was no increase in alveolar/capillary barrier permeability or lung cellular injury. The results might suggest that high temperature (35 degrees C) affects the pulmonary defense mechanism.
