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991.
992.
Several point mutations of p16INK4a were studied by site-specific mutagenesis and functional analysis to assess the effects of these mutations on the function of the protein. These mutations were reported in several malignancies. Three deletional mutants of p16INK4a were also analyzed to reveal the relationship between p16INK4a and p15INK4b and to test the importance of the ankyrin repeats observed in both proteins. We studied the activity of these mutants using the yeast two-hybrid system and an in vitro kinase assay. Our results suggest that point mutations in the conserved ankyrin consensus affect the activity of p16INK4a. However, not all of the point mutations observed in tumors have a detectable effect on the activity. The COOH-terminal region of p16INK4a is not required for the protein to bind and to inhibit CDK4, but the deletion of the 4th ankyrin repeat abolished the activity completely. 相似文献
993.
A 42-year-old Chinese woman developed 3 weeks of swinging fever, rash, malaise, and discomfort at the right upper quadrant of the abdomen. Acute Clonorchis sinensis infection eventually became evident and the patient responded to praziquantel. Although acute infestation is usually asymptomatic, occasional cases suffer severe symptoms and present difficulties in clinical diagnosis. Clonorchiasis is endemic in South East Asia. With the increasing popularity of travel to these countries and the global migration of Asians, physicians need to be aware of the condition. Treatment with praziquantel is effective and prevents the serious sequelae of chronic infection. 相似文献
994.
995.
To determine whether part of the anti-inflammatory effects of prostaglandin E2 (PGE2) was related to inhibition of T cell interactions with endothelial cells (EC), the effects of PGE2 and other cAMP-elevating agents on the transendothelial migration of human T cells was examined. Although PGE2 did not effect T cell binding to EC, concentration-dependent inhibition of the transendothelial migration of T cells through unstimulated or IL-1-activated EC was observed. PGE2 inhibited the function of both T cells and EC, with maximal inhibition observed when both T cells and EC were treated with PGE2. However, the inhibitory action of PGE2 could not be ascribed to an effect on the adhesion receptor pair, CD11a/CD18-CD54. The inhibitory effect of PGE2 seemed to relate to its capacity to elevate cellular cAMP levels, because 3-isobutyl-1-methylxanthine enhanced PGE2 activity and dibutyryl cAMP and forskolin also inhibited transendothelial migration. The inhibitory effect of PGE2 and the other cAMP-elevating agents on the function of T cells related in part to suppression of their intrinsic locomotory behavior as random migration in the absence of EC was blocked. In EC, PGE2 and the other cAMP-elevating agents increased the barrier function of EC as evidenced by a decrease in the diffusion of [3H]mannitol through the endothelium. These results indicate that part of the anti-inflammatory action of PGE2 relates to its capacity to suppress the transendothelial migration of T cells by cAMP-mediated alterations in the function of both T cells and EC. 相似文献
996.
RM Conry MB Khazaeli MN Saleh V Ghetie ES Vitetta T Liu AF LoBuglio 《Canadian Metallurgical Quarterly》1995,18(4):231-241
In a phase I trial, eight patients with non-Hodgkin's B-cell lymphoma received mouse IgG1k monoclonal antibody HD37 specific for CD19 conjugated to deglycosylated ricin A chain (dgA) administered in four doses at 4-h intervals with total doses ranging from 4-12 mg/m2. This schedule generated serum levels of immunotoxin which were sustained over 36 h. The plasma half-life of HD37-dgA was 17 +/- 4 (SD) h. The HD37-dgA conjugate was stable in vivo as demonstrated by serum levels of HD37-dgA conjugate comparable to those of total HD37 antibody. Peak serum levels attained after the fourth dose ranged from 0.36 to 5.63 micrograms/ml. Two of seven evaluable patients developed modest human anti-immunotoxin antibody responses. Toxicity in patients 1-7 consisted of dose-dependent capillary leak syndrome with hypoalbuminemia, orthostatic hypotension, and weight gain. Patient 8 died on day 8 with severe capillary leak, bronchopneumonia, and rhabdomyolysis. All patients had progressive disease at 4 weeks except patient 8, who exhibited a near-complete remission before his death. This intensive schedule appears to produce inordinate toxicity with a maximal tolerated total dose of 8 mg/m2. 相似文献
997.
998.
We report a case of traumatic penile amputation which occurred accidentally during a ritual circumcision in a 10-year-old boy. A successful penile reattachment was accomplished. Additionally, we discussed the causes and prevention of this condition. 相似文献
999.
1000.