具有甲状腺素运载蛋白Asp18Gly变异并表现为反复蛛网膜下腔出血及浅表性铁质沉着的家族性软脑膜淀粉样变性

Objectives: To report the clinical features of two Japanese brothers with fami lial leptomeningeal amyloidosis, showing a causative gene abnormality of a trans thyretin (TTR) variant Asp18Gly, previously reported only in a Hungarian family. Methods: The authors reported on a 42 year old man (patient 1) and his 45 year o ld brother (patient 2), both suffering from subarachnoid haemorrhage (SAH) witho ut and with hydrocephalus, respectively. DNA sequences of the TTR gene were dete rmined in both patients and the patientsclinical features described. A surgica l biopsy of the leptomeninges was performed on patient 1. Results: DNA sequence analyses demonstrated the glycine for aspartate substitution at position 18 of the TTR variant. Both patients revealed pyramidal tract signs and cerebellar at axia. Audiometric studies showed bilateral, mild sensori neural hearing loss in the patients whose cerebrospinal fluid (CSF) protein levels increased. T1 weigh ted MRI after contrast administration showed diffuse leptomeningeal enhancement along the Sylvian fissures and over the surface of the brainstem, cerebellum, an d spinal cord. Gradient echo T2.weighted MRI showed superficial siderosis mainly in the cerebellum. A biopsy of the leptomeninges was obtained from the spinal c ord of patient 1. While performing the biopsy, the authors observed the varicose , elongating, and fragile veins on the dorsal surface of the spinal cord. Immuno histochemical study revealed marked deposits of TTR derived amyloid on his lepto meninges. Conclusions: This is the second report of familial leptomeningeal amyl oidosis with an Asp18Gly TTRgene mutation, clinically causing only CNS symptoms. Repeated SAH from fragile veins on the dorsal surface of the spinal cord seemed to induce superficial siderosis of the CNS. So far, there have been two reliabl e hallmarks leading to the diagnosis of leptomeningeal amyloidosis: diffuse lept omeningeal enhancement on contrast MRI and greatly increased CSF protein content . This study has contributed a third hallmark: the presence of superficial sider osis is useful in diagnosing leptomeningeal amyloidosis.

弥散加权磁共振(DWI)异常可作为Creutzfeldt-Jakob病(CJD)的一个早期诊断指标

Objective: To evaluate the usefulness of diffusion weighted MRI (DWI) for the early diagnosis of Creutzfeldt Jakob disease (CJD). Methods: Thirty six consecutive patients (age 56 to 82 years) were enrolled, and 26 were examined byDWI.Ninewere definite based on theWorld Health Organization criteria, and 27 were probable. The percentages ofDWI abnormalities, periodic sharp wave complexes (PSWCs) on the EEG, detection of CSF 14- 3- 3 protein, and increase of CSF neuron- specific enolase (>25 ng/mL) on the first examination were compared. For DWI, 32 patients (age 31 to 84 years) who showed progressive dementia or impaired consciousness served as disease controls. Results: The percentage of DWI abnormalities was 92.3% , of PSWCs 50.0% , of 14- 3- 3 protein detection 84.0% , and of NSE increase 73.3% . Two of the 32 control subjects were falsely positive on DWI. The sensitivity of DWI was 92.3% (95% CI 74.8 to 99.5% ) and specificity 93.8% (95% CI 79.2 to 99.2% ). In 17 patientswho did not showPSWCs on the first EEG, abnormalDWI findings were still clearly detec ted. Four patients who were negative for 14- 3- 3 protein also showed DWI abnormalities. DWI abnormalities were detected as early as at 3 weeks of symptom duration in four patients in whom PSWCs were not yet evident. Conclusions: DWI can detect characteristic lesions in the majority of patients with CJD regardless of the presence of PSWCs. DWI was the most sensitive test for the early clinical dia gnosis of CJD; consideration should be given to its inclusion in the clinical diagnostic criteria of CJD.

尿8-羟基脱氧鸟苷水平作为评估帕金森病进展的生物学标记物

8-Hydroxydeoxyguanosine (8-OHdG) has been used to evaluate oxidative stress. The authors investigated urinary 8-OHdG levels in 72 patients with Parkinson d isease (PD) and in normal and disease control groups. The mean urinary 8-OHdG i ncreased with the stage of PD and was not influenced by the current dose of DOPA . Our results suggest that urinary 8-OHdG is a potentially useful biomarker for evaluating the progression of PD.

日本系统性硬化症患者中的抗DNA拓扑异构酶Ⅱα自身抗体

The pathogenesis and etiology of systemic sclerosis (SSc) remain unknown, but the presence of several autoantibodies is recognized as one of its prominent features. The clinical significance of anti- DNA topoisomerase Ⅱ α antibody (anti- topo Ⅱ α Ab) remains unknown in Japanese patients with SSc. To determine the prevalence and clinical correlation of anti- topo Ⅱ α Ab in Japanese patients with SSc. Serum samples were obtained from 103 Japanese patients with SSc. Control serum samples were obtained from 43 healthy Japanese volunteers. Anti- topo Ⅱ α Abs were determined by enzyme linked- immunosorbent assay.IgG anti- topo Ⅱ α Ab levels were significantly increased in SSc patients (n=103) compared to normal controls (n=43; P<0.005). IgG or IgM anti- topo Ⅱ α Ab was detected in 19% (20/103) of SSc patients when absorbance values higher than the mean+ 2SD of control serum samples were considered positive. By contrast, IgG or IgM anti- topo Ⅱ α Ab was observed in only 7% (3/43) of healthy individuals. The presence of pulmonary fibrosis was more frequently detected in SSc patients with IgG anti- topo Ⅱ α Ab than those without the Ab (P<0.05). Moreover, % DLco and % VC were significantly decreased in SSc patients with anti- topo Ⅱ α Ab relative to those without the Ab (P<0.05 and P<0.01, respectively). The elevated levels of both erythrocyte sedimentation rate and C- reactive protein were also more frequently observed in SSc patients positive for IgG anti- topo Ⅱ α Ab (P<0.005). The results of the present study indicate that anti- topo Ⅱ α Ab represent one of the autoantibody specificities detected on SSc patients and may be regarded a serological marker of pulmonary fibrosis in Japanese patients with SSc.

恶性黑色素瘤患者血清中可溶性细胞间黏附分子1及可溶性L选择素水平的临床意义

Although several molecules have been evaluated as tumor markersof malignant melanoma (MM) progression, there are fewavailable markers sensitive enough to detect recurrence or metastasis. The objective of the present study was to determineclinical significance of serum soluble adhesion molecules in the monitoring of progression in patients with MM. Serum levels of soluble L- selectin (sL- selectin), sE- selectin, sP- selectin, and soluble intercellular adhesion molecule- 1 (sICAM- 1) were determined by ELISA in 57 MM patients. In a retrospective longitudinal study, nine serum samples from two MM patients were analyzed during a follow- up period of 4.0 and 4.3 years, respectively. Serum sICAM- 1 levels in MM patients were significantly higher than those in healthy controls and tended to be elevated as the disease stage progressed. In contrast, serum sL- selectin levels were significantly lower inMMpatients compared to healthy controls and tended to decrease as the disease stage progressed. There was no significant difference in serum sE- selectin and sP- selectin levels between MM patients and normal control. In a longitudinal study, increased sICAM- 1 and decreased sL- selectin levels were generally associated with the progression of MM. These results suggest that monitoring both sICAM- 1 and sL- selectin is available to evaluate the progression of MM.