The relationship between the DNA replication and spindle checkpoints of the cell cycle is unclear, given that in most eukaryotes, spindle formation occurs only after DNA replication is complete. Fission yeast rad3 mutant cells, which are deficient in DNA replication checkpoint function, enter, progress through, and exit mitosis even when DNA replication is blocked. In contrast, the entry of cds1 mutant cells into mitosis is delayed by several hours when DNA replication is inhibited. We show here that this delay in mitotic entry in cds1 cells is due in part to activation of the spindle checkpoint protein Mad2p. In the presence of the DNA replication inhibitor hydroxyurea (HU), cds1 mad2 cells entered and progressed through mitosis earlier than did cds1 cells. Overexpression of Mad2p or inactivation of Slp1p, a regulator of the anaphase-promoting complex, also rescued the checkpoint defect of HU-treated rad3 cells. Rad3p was shown to be involved in the physical interaction between Mad2p and Slp1p in the presence of HU. These results suggested that Mad2p and Slp1p act downstream of Rad3p in the DNA replication checkpoint and that Mad2p is required for the DNA replication checkpoint when Cds1p is compromised.
We report a 40-year-old man with severe hypokinesis as paraneoplastic manifestation of a microscopic "carcinoma in situ" of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti-Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti-Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits.
Keywordsanti-Ma2 paraneoplastic encephalitis; hypokinesis; Parkinsonism; intratubular germ-cell neoplasia Paraneoplastic anti-Ma2-associated encephalitis usually results in limbic, diencephalic, and brainstem dysfunction. Predominant hypokinesis, however, has been rarely reported. 1 We report a patient with this disorder who developed severe hypokinesis as predominant clinical features, and whose underlying neoplasm was a microscopic "carcinoma in situ" of the testis.
CASE REPORTSA 40-year-old Japanese man developed diplopia and unsteadiness of gait in July 2004. Within the next 2 months he developed progressive difficulty in moving his extremities, and by the middle of August, he could not get out from bed. His facial expression became markedly reduced and the voice barely audible. He also developed severe micrographia. The patient was initially seen by a psychiatrist who prescribed antidepressants, without significant improvement of symptoms. By the end of August, he had difficulty in swallowing, and tremor when holding objects. He looked anxious, irritable, and became very sensitive to auditory stimuli. In September, the patient was seen at a local hospital and found to have reduced
Soymilk was prepared by ohmic heating. Heating time decreased as the applied voltage was increased.Precipitation, viscosity and surface hydrophobicity of protein in the soymilk were increased with the decrease in voltage applied. Voltages of 50 and 100 V resulted in a higher heating rate and consequent formation of a larger amount of protein particles (soluble aggregates), ranging from 40 to 120 nm in size, than the other conditions. Furthermore, soymilk prepared by ohmic heating at 50 or 100 V was converted into firmer tofu curd than that at 30 V. Ohmic heating at 30 V was thought to form larger protein particles than that at 50 and 100 V, and the resultant larger sized aggregates are considered to result in inferior tofu curd texture.
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