Is the maintainance of the C-terminus domain of dystrophin enough to ensure a milder Becker muscular dystrophy phenotype?

The severe Duchenne muscular dystrophy (DMD) and the more benignBecker type (BMD) are allelic conditions, controlled by a defectivegene at Xp21, caused by the absence (DMD) or a defect in quantityor quality (BMD) of the protein dystrophin. It has been suggestedthat the C-terminus domain of dystrophin is fundamental to ensurethe proper protein sub-cellular localization and function. Wewish to report our dystrophin findings in 4 among 142 DMD patientsstudied for DNA deletions and dystrophin analysis. Althoughthey have a severe clinical course, a positive dystrophin immunofluorescencepattern was seen using C-terminal antibody, and a dystrophinband of reduced molecular weight (corresponding to their DNAdeletions), but which maintained the C-terminus was seen throughWestern blot (WB). Based on these findings, we suggest thatin order to partially maintain its function, resulting in amilder phenotype, dystrophin may carry large internal deletionsbut in addition to the C-terminus, the region encompassing boththe N-terminus and the proximal region of the rod domain cannotbe absent. Therefore, the prognosis of a Becker phenotype ina young patient should be done with caution if based only onthe presence or not of dystrophin.     

Maltoma of the thyroid and Sjögren’s syndrome in a woman with Hashimoto’s thyroiditis

We report the case of a 70-yr-old woman with maltoma of the thyroid, Sjögren’s syndrome, and a history of Hashimoto’s thyroiditis. The patient underwent a total thyroidectomy for a recently growing mass of the thyroid, while being treated with l-thyroxine for Hashimoto’s thyroiditis. Postoperatively, routine histologic examination was consistent with the diagnosis of chronic lymphocytic thyroiditis of autoimmune etiology. Three years later, the patient presented with high temperature, anorexia, and coughing. This time, a microscopic examination of deeper thyroid tissue sections and an immunohistochemical study revealed a low-grade, non-Hodgkin lymphoma, MALT type. Simultaneously, the diagnosis of Sjögren’s syndrome was established and the patient is currently under investigation for generalized lymphoma. This case clearly demonstrates the difficulty in differentially diagnosing Hashimoto’s thyroiditis from low-grade MALT lymphoma by the use of routine histologic examination.     

Changes in the cerebrospinal-fluid monoamines in rats with an immunoneutralization of the subcommissural organ-Reissner’s fiber complex by maternal delivery of antibodies

The subcommissural organ (SCO) is a brain gland secreting glycoproteins into the cerebrospinal fluid (CSF), where they aggregate forming the Reissner’s fiber (RF). By the continuous addition of newly released glycoproteins, RF grows along the cerebral aqueduct, fourth ventricle, and central canal of the spinal cord. At the filum, RF-glycoproteins escape from the central canal and reach the local blood vessels. Despite a century of research, the function of the SCO remains elusive. The aim of the present investigation was to test the hypothesis that RF-glycoproteins, by binding and transporting monoamines out of the CSF, participate in the clearance of these compounds. A protocol was designed that led to the permanent immunoneutralization of the SCO through the maternal delivery of antibodies. This was achieved by transplacental transfer to the fetuses, and through the milk to the pups, of specific antibodies against SCO secretory proteins. The antibodies reached the CSF of the fetuses and pups and blocked the RF formation during the first months of life. Some of these animals died during the first postnatal weeks; those who survived displayed a rise in the CSF concentration of several monoamines, l-DOPA being the one with the highest rise. Adult rats transiently deprived of RF by a single injection of anti-RF antibodies into the CSF showed a transient rise in the CSF concentration of l-DOPA. All these results support the hypotheses that the SCO-RF complex participates in the clearance of monoamines from the CSF. Received: 08 October 1998 / Accepted: 24 March 1999     

Hodgkin’s lymphoma in a patient with Jo-1 syndrome

Jo-1 syndrome is an autoimmune disease with autoantibodies against the histidyl tRNA synthetase. Characteristic clinical findings include inflammatory myopathy and interstitial lung disease. We present the first case of a patient with Jo-1 syndrome (positive Jo-1 autoantibodies, myositis, interstitial alveolitis) who developed Hodgkin’s lymphoma of nodular-sclerosing type. Thus, patients with Jo-1 syndrome and immunosuppressive therapy similar to other patients with autoimmune disease are at risk to develop lymphomas and should therefore be monitored carefully.     

Haemangiopericytoma of the thyroid gland in combination with Hashimoto’s disease

We present a hitherto unique case of haemangiopericytoma (HP) of the thyroid gland in a 15-year-old female patient suffering from Hashimotos disease for several months. Since angiogenesis has been discussed to play a major role in both diseases, we examined the expression of vascular endothelial growth factor (VEGF), VEGF receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs). Most interestingly, strong expression of PDGFR and was found in spindle-shaped tumour cells and tumour vessels in HP, while VEGF and VEGFR type I and -II were negative in these regions. In contrast, VEGF was expressed in the lymphoid infiltrate of Hashimotos disease. Since PDGFR- is commonly expressed in pericytes, we suggest that the strong expression discovered in this study further supports the view that HP is derived from pericytes. The combination of HP and Hashimotos disease is most probably a coincidental event. However, this case confirms previous reports demonstrating that in patients with Hashimotos disease different neoplasias can occur.     

Metaplasia of the parietal layer of Bowman’s capsule in a cat

A 5-year-old male cat presented at the clinic with status epilepticus following long-term sodium valproate treatment. On clinical examination, the cat lost consciousness and had frequent seizures. The animal’s condition did not improve by intravenous administration of diazepam. Serum biochemical abnormalities included marked uremia and hyperphospatemia. A provisional diagnosis of chronic kidney disease was made based on laboratory data. Further investigation and treatment was declined by the owner, and the cat was euthanized. Necropsy was performed, and on histopathological examination, numerous lesions were observed within some of the glomeruli. Specifically, metaplasia of the parietal cells was noted, with a change from short cuboidal to tall columnar cells within Bowman’s capsule. These cells were composed of round to oval vesicular nuclei with prominent nucleoli. The underlying basement membrane was thickened, and there was evidence of pre-glomerular fibrosis.     

Analysis of the parameters of oxidative stress in patients with Parkinson’s disease

The increasing data provides enough evidences confirming the involvement of free radicals and other reactive oxygen species (ROS) superoxide radical ( ^. O ₂ ^? ), nitric oxide (NO ^. ), hydrogen peroxide (H₂O₂) and hydroxyl radicals ( ^. OH) in a number of physiological and pathological processes. Imbalance between levels of ROS resulting in the body and the capacity of antioxidant defense mechanisms occur oxidative stress (OS). OS is related to a number of structural and functional damages to cells and is involved in the pathogenesis of many diseases, including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis, and Huntington disease. Defects in oxidative phosphorylation and oxidative damage play an important role in neurodegenerative diseases. The aim of this study was to investigate some biomarkers of OS such as the level of lipid peroxidation measured as malondialdehyde (MDA) reactive products and activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the blood of PD patients compared with control group of healthy volunteers. By the present research we report higher levels of MDA products and an imbalance in SOD and CAT enzyme activities in PD patients compared to the control group.     

Disrupted Collagen Architecture in the Crystal Structure of a Triple-Helical Peptide with a Gly → Ala Substitution

The crystal structure of the collagen-based peptide (Pro-Hyp-Gly)₄-Pro-Hyp-AIa-(Pro-Hyp-Gly)₅ has provided for the first time a highly detailed picture of the architectural elements that come into play in the collagen triple helix. The center of the molecule, which harbors a Gly → Ala substitution, shows subtle conformational changes that result in a local untwisting of the triple helix. The characteristic hydrogen bonding pattern of collagen triple helices is replaced by interstitial water bridges. These effects may be relevant to the diseased states derived from Gly → X mutations in collagens. The possible implications of this disrupted architecture for collagen assemblies are discussed.     

Parasitic nodule of the thyroid in a patient with Graves’ disease

 We report a case of a parasitic nodule of the thyroid in a patient with Graves’ disease, which mimicked a lymph node metastasis from a primary occult thyroid carcinoma. The patient was a 67-year-old Japanese woman with a past history of subtotal thyroidectomy for Graves’ disease, who was referred to our hospital because of a right cervical mass. A lymph node-like lesion measuring 1.5 cm in diameter was palpable, distinct from the remnant of the right thyroid lobe. Thyroid scintigraphy using ¹²³I-Na revealed a hot lesion at the upper lateral portion of the right thyroid lobe, and this was resected. Microscopically, the mass showed thyroid follicles with lymphocytic infiltration and lymphoid follicles. Clear ground glass nuclei, nuclear grooving and intranuclear inclusions were not observed. No morphological evidence of the lymph node was found in the mass by reticulin staining. Parasitic nodules of the thyroid in patients with Graves’ disease may mimic a metastatic carcinoma of the thyroid. Received: 21 January 1998 / Accepted: 15 April 1998     

Hydrocephalus and Hirschsprung’s disease with a mutation of L1CAM

Abnormalities of the L1CAM gene, a member of the immunoglobulin gene superfamily of neural-cell adhesion molecules, are associated with X-linked hydrocephalus and some allelic disorders. Hirschsprungs disease (HSCR) is characterized by the absence of ganglion cells and the presence of hypertrophic nerve trunks in the distal bowel. There have been three reports of patients with X-linked hydrocephalus and HSCR with a mutation in the L1CAM gene. We report three more patients with similar conditions. We suspect that decreased L1CAM may be a modifying factor in the development of HSCR.     

Multimodal MRI of the hippocampus in Parkinson’s disease with visual hallucinations

Visual hallucinations carry poor prognosis in Parkinson’s disease. Here we tested the hypothesis that the hippocampus and visuospatial memory impairment play a central role in the pathology of PD with visual hallucinations. Multimodal magnetic resonance imaging of the brain was carried out in 12 people with PD and visual hallucinations; 15 PD individuals without hallucinations; and 14 healthy controls. Age, gender, cognitive ability, and education level were matched across the three groups. PD patients were taking dopaminergic medication. Hippocampal volume, shape, mean diffusivity (MD), and functional connectivity within the whole brain were examined. Visuospatial memory was compared between groups, and correlations with hippocampal MD, functional connectivity, and the severity of hallucinations were explored. There were no macrostructural differences across groups, but individuals with hallucinations had higher diffusivity in posterior hippocampus than the other two groups. Visuospatial memory was poorer in both PD groups compared to controls, and was correlated with hallucinations. Finally, hippocampal functional connectivity in the visual cortices was lower in those with hallucinations than other groups, and this correlated with visuospatial memory impairment. In contrast, functional connectivity between the hippocampus and default mode network regions and frontal regions was greater in the PD hallucinators compared to other groups. We suggest that hippocampal pathology, which disrupts visuospatial memory, makes a key contribution to visual hallucinations in PD. These findings may pave the way for future studies of imaging biomarkers to measure treatment response in those with PD who are most at risk of poor outcomes.     

Investigation of the Esophageal Rho-kinase Expression in Patients with Barrett’s Esophagus

Abstract

The mechanisms responsible for the malignant transformation in Barrett’s esophagus (BE) are still poorly understood. The authors have evaluated the role of Rho-kinase (ROCK1 and ROCK2) expressions in patients with BE. All patients underwent upper gastrointestinal system endoscopy, which was confirmed histologically. Real-time PCR revealed no marked change in gene expressions of ROCK1 and ROCK2 at mRNA levels in BE when compared to controls. Immunohistochemical and western blot analyses showed no change in ROCK1 and ROCK2 protein expressions in BE. This study demonstrates that Rho-kinase gene and protein expressions are not modified in BE.     

X-Linked agammaglobulinemia in a child with Klinefelter’s syndrome

Bruton’s agammaglobulinemia is a rare X-linked humoral immunodeficiency manifesting with recurrent bacterial infections early in life. Klinefelter’s syndrome caused by an additional X chromosome is the most common sex chromosome disorder. A previously unreported association of these two conditions is described here.     

Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese

Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigen. The cytotoxic T-lymphocyte antigen-4 (CTLA4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3UTR of the CTLA4 gene, in which the three single-nucleotide polymorphisms (SNPs) CT60, JO31, and JO30 were strongly associated with AITD. In order to determine the association of the CTLA4 gene with AITD in the Japanese, case-control association analysis for the four SNPs of the CTLA4 gene using 380 AITD patients and 266 healthy controls was done. Among the SNPs examined, the SNP JO31 was most significantly associated with AITD in the Japanese, whereas the association of the JO30 with AITD was not observed. The frequency of the disease-susceptible G allele of the JO31 of the Japanese control was higher than that of the Caucasians (67.1% vs 50.2%); however, the G allele of the JO31 was associated with Graves disease (GD) (67.1% vs 76.3%, P=0.0013) and AITD in the Japanese (67.1% vs 74.2%, P=0.0055). Furthermore, the G allele of the JO31 was associated with the increased risk for GD [P=0.0051, odds ratio (OR)=1.7] and AITD (P=0.016, OR=1.5) in a dominant model. These results suggested that the CTLA4 gene is involved in the susceptibility for GD and AITD in the Japanese.     

Assessment of the Efficacy of Preventive Therapy with Chaperone Inducer U133 in a Model of the Preclinical Stage of Parkinson’s Disease in Elderly Rats

Neuroscience and Behavioral Physiology - Parkinson’s disease (PD) is a chronic relentlessly progressive neurodegenerative disease mainly affecting dopamine (DA)-ergic neurons in the...     

α-Synuclein in the olfactory system of a mouse model of Parkinson’s disease: correlation with olfactory projections

Olfactory deficits are an early feature of Parkinson’s disease (PD). Neuropathologically, α-synucleinopathy (Lewy bodies and neurites) is observed earlier (stage 1) in the olfactory system than in the substantia nigra (stage 3), and this could underlies the early olfactory symptoms. In the present report, we analyzed the distribution of α-synuclein deposits in tertiary olfactory structures (anterior olfactory nucleus, olfactory tubercle, piriform cortex, posterolateral cortical amygdala and lateral entorhinal cortex) of homozygous transgenic mice (aged 2–8 months) overexpressing the human A53T variant of α-synuclein. To address the hypothesis of progressive α-synucleinopathy within the olfactory system, the distribution of α-synuclein was analyzed in conjunction with tracer injections into the main olfactory bulb. The time-course of α-synuclein expression revealed a significant increase in the piriform cortex at the age of 8 months compared to other brain structures. Tracing experiments revealed that olfactory projections are reduced in homozygous as compared to wild type animals. Double-labeling experiments show labeled axonal collaterals of mitral cells entering layer II of the piriform cortex in close proximity to α-synuclein-positive cells. To our knowledge, this is the first study addressing the progression of α-synuclein expression in a vulnerable neuronal pathway in PD.