Both ATP hydrolysis by myosin and the accompanying cyclic association-dissociation of actin and myosin are essential for muscle contraction. It is important for understanding the molecular mechanism of contraction to know the three-dimensional locations of the two major functional sites of myosin: the ATPase site and the actin-binding site. We have determined the position of the ATPase site of myosin using three-dimensional image reconstruction from electron micrographs and site-specific labelling with the avidin-biotin system. The ATPase site is about 5 nm from the tip of the myosin head and is about 4 nm away from the actin-binding site of myosin. This is the first report of the three-dimensional location of an enzyme active site by electron microscopy.

Actins↗

PubMedDate not supplied

Identification of a Notch3 mutation in a Japanese CADASIL family. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease that is characterized by recurrent stroke episodes and focal neurologic deficits progressing to pseudobulbar palsy and dementia. The causative gene is the Notch3 gene on chromosome 19, and 22 missense mutations have been identified in Caucasian patients to date. To perform mutational analysis of the Notch3 gene, we identified its exon intron boundaries and prepared sets of primers for amplification of each exon. Using these primers, we determined the Notch3 gene in a Japanese family with CADASIL symptoms and found a missense mutation (Arg133Cys) in exon 4. The mutation was heterozygous and cosegregated with the disease. Thus, the Notch3 gene is responsible for CADASIL in patients across different ethnic groups.

Dementia, Multi-Infarct↗

PubMedDate not supplied

FDG-PET in differential diagnosis and grading of chondrosarcomas.

PURPOSE: The purpose of this work was to investigate the usefulness of PET with [18F]2-deoxy-2-fluoro-D-glucose (FDG) in the differential diagnosis and grading of chondrosarcomas. METHOD: Four enchondromas, one osteochondroma, and six chondrosarcomas were prospectively studied by FDG-PET. The significance of the standardized uptake value (SUV) was evaluated in comparison with clinical, radiological, and histopathological findings of the tumors. RESULTS: The SUV ranged from 0.7 to 1.3 (mean 0.96+/-0.22) in benign cartilage tumors and from 1.3 to 3.3 (2.23+/-0.80) in chondrosarcomas. This SUV difference between benign and malignant tumors was statistically significant (p = 0.011) in contrast to considerable overlap of clinical and radiological findings. Among chondrosarcomas, the SUV of one Grade I tumor was 1.3; those of four Grade II tumors were 1.3, 1.9, 2.5, and 3.1; and that of one Grade III tumor was 3.3. CONCLUSION: Our preliminary study showed that FDG-PET could be an objective and quantitative adjunct in the differential diagnosis and grading of chondrosarcomas.

Adult↗

PubMedDate not supplied

Possibility of pre-operative diagnosis of lymph node metastasis based on morphology.

BACKGROUND/AIMS: The accuracy of pre-operative diagnosis of lymph node metastasis is insufficient. Our aim was to define the possibility of diagnosing metastatic lymph nodes based on morphology. METHODOLOGY: One hundred and fifty-seven patients with pre-operatively untreated esophageal squamous cell carcinoma underwent resection, 5334 lymph nodes were isolated, and the short and long diameters were measured. We tried to construct a linear regression line for metastasis rate versus lymph node size (long diameter classified at intervals of 1 mm) by each location. The ratio of short diameter to long diameter (SL ratio) of metastasis-positive lymph nodes was compared with that of negative ones at each location. RESULTS: Gradient and intercept of overall regression line was 0.0213 and 0.0101, respectively, and the long diameter producing a metastasis rate of 80% (LD80) was 37.1 mm. Metastasis-positive lymph nodes larger than calculated LD80 represented no more than 9.5% of all the corresponding metastasis-positive nodes. The locations with significant difference of SL ratio between metastasis-positive and negative ones were limited to right cardiac, left gastric artery, thoracic paratracheal, bifurcation, and the highest mediastinal nodes. CONCLUSIONS: There is a low possibility that lymph node metastasis can be exactly diagnosed pre-operatively based on the size and morphology.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Lupus cystitis and performation of the small bowel in a patient with systemic lupus erythematosus and overlapping syndrome.

We describe a patient with systemic lupus erythematosus (SLE) and overlapping syndrome who had repeated gastrointestinal (GI) symptoms such as nausea, vomiting and malabsorption. With a subacute process, she developed paralytic ileus and contracted bladder, and died of perforation of the ileum. When 13 reported cases with lupus cystitis were reviewed, an extremely strong correlation between GI and urinary tract symptoms was observed, indicating the presence of a unique subgroup of SLE.

Adult↗