Effects of maxillary protraction combined with chin-cap therapy in unilateral cleft lip and palate patients.

OBJECTIVE: This study investigated the treatment effects of maxillary protraction combined with chin-cap therapy in complete unilateral cleft lip and palate patients at the deciduous and early mixed dentition stages. METHOD: Twenty-six Japanese children (10 boys and 16 girls) with complete unilateral cleft lip and palate were examined. All had undergone pushback operations for palatal repair at approximately 18 months of age. Maxillary protraction began between 5 and 7 years of age and continued for 10 to 38 months. Lateral cephalograms were used to analyze skeletal changes during the first and second years of treatment, and the relationship between pretreatment midfacial morphology and forward displacement of the maxilla during the first year was investigated. RESULTS AND CONCLUSIONS: During the first year of treatment, the mean increase in the ANB angle for all cases was 2.37 degrees. The forward displacement of the maxilla varied considerably, from 0.23 mm to 3.03 mm. The treatment response was significantly smaller in the second year, and no benefit from treatment longer than 1 year was established. The amount of maxillary forward displacement was significantly correlated with the pretreatment posterior upper facial height. Patients with smaller posterior upper facial height showed a poorer treatment response, whereas patients with a greater posterior upper facial height responded better to treatment. Individual differences in maxillary growth acceleration may be related to growth inhibition associated with postsurgical scar tissue on the palates.     

Mortality, major cause of moribundity, and spontaneous tumors in CD-1 mice

Mortality, major causes of moribundity, and spontaneous tumors in CD-1 mice were studied in 891 males and 890 females, which were used as controls in 11 different 2-year chronic and oncogenicity studies during the past 5 years. Average mortality of males and females at 83 weeks of age was 32.6% and 28.6%, respectively, and at 109 weeks of age was 66.4% and 63.3%, respectively. Mortality was significantly lowered in males and females born after 1980 in accordance with an abruptly decreased occurrence of systemic amyloidosis in these animals. The major cause of death or moribundity included systemic arteritis, systemic amyloidosis, auricular thrombosis, glomerulosclerosis, lymphoma, and pulmonary adenocarcinoma in both sexes. Dysuria and hepatocellular carcinoma in males and mammary adenocarcinoma in females were also critical lesions. The major tumors occurring at more than 3% incidence were systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver and adenoma/adenocarcinoma of the Harderian gland for males, and systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver, leiomyoma/leiomyosarcoma of the uterus, adenoma/adenocarcinoma of the pituitary (anterior), adenoma/adenocarcinoma of the mammary gland and adenoma/adenocarcinoma of the Harderian gland for females. Intralaboratory heterogeneities in the incidence were recorded as follows: systemic lymphoma in 1 of 11 control groups (1/11) and adenoma/adenocarcinoma in 1/11 for males, and systemic lymphoma in 3/11, adenoma/adenocarcinoma of the lung in 2/11, adenoma/adenocarcinoma of the liver in 1/11, and adenoma/adenocarcinoma in 1/11 for females.     

Recurrent meningioma with malignant changes and extracranial multiple metastases

A case of recurrent meningioma with malignant change and extracranial multiple metastases is reported. A 51-year-old female was operated on and left parasagittal meningioma was extirpated by Simpson grade II. Histological diagnosis was fibroblastic and transitional meningioma with slight atypism. Six years later, however, the tumor (transitional meningioma with slight mitosis) recurred in the same portion and was removed again by Simpson grade II. Further more, four years after the second operation, bilateral parasagittal meningioma (atypical meningioma; transitional type) was extirpated by Simpson grade I including superior sagittal sinus and falx. Only eight months after the last operation, a few tumors with central necrosis were demonstrated in the bilateral parasagittal area on a computerized tomography scan and she received radiation therapy. But the tumor had metastasized to the extracranial multiple organs including lungs, liver, pancreas, adrenal gland, muscles, multiple bones and lymph nodes. Post mortem diagnosis was malignant meningioma. We reviewed and discussed the characteristics of metastasizing meningioma, the effectiveness of radiation therapy on the prevention of recurrence of meningioma and the curative effect of radiation therapy for recurrent or metastasized meningioma.     

5-Fluorouracil for trabeculectomy in glaucoma

The effect of 5-fluorouracil (5-FU) subconjunctival injection on the bleb formation and intraocular pressure (IOP) following trabeculectomy was studied in 18 glaucoma patients (20 eyes) with poor surgical prognosis. The results were analyzed by means of life tables and compared with those of 24 glaucoma eyes that had undergone trabeculectomy without postoperative administration of 5-FU after a previous repeat trabeculectomy that had failed. The surgical techniques and postoperative care were virtually identical between the eyes treated with 5-FU and eyes that had undergone repeat trabeculectomy, except that the latter group did not receive 5-FU postoperatively. At the end of 18-month follow-up, the success probability was 68.2% in the 5-FU treated eyes, and it was already as low as 10% in the nontreated eyes at the end of the 14-month follow-up. The difference was statistically highly significant (P less than 0.001). Postoperative, subconjunctival injection of 5-FU appears to improve the prognosis following trabeculectomy in patients with a poor surgical prognosis.     

PRELIMINARY OBSERVATION ON PANCREATIC DUCT ADENOCARCINOMA INDUCED BY INTRADUCTAL ADMINISTRATION OF N-ETHYL-N' -NITRO-N-NITROSOGUANIDINE IN DOGS

Pancreatic duct adenocarcinoma was induced by intraductal administration of N-ethyl-N'-nitro N-nitrosoguanidine (ENNG) in two mongrel dogs. A dog received a total dose of 595 mg of ENNG during 12 months and was sacrificed. Duct obstruction was detected by pancreatography and duct adenocarcinoma was found. Another dog was given a total dose of 350 mg of ENNG during 8 months and was sacrificed 26 months after the first administration of the carcinogen. Duct adenocarcinoma was found. No pancreatic tumors were found in 2 dogs given intraperitoneal N-nitrosobis(2-oxo-propyl)amine at a total dose of 4000 mg or in 2 dogs given Tween 60 only. These results suggest that the direct presence of a carcinogen in the pancreatic duct was able to induce duct adenocarcinoma in dogs.     

Role of proteolytic activation of protein kinase Cdelta in oxidative stress-induced apoptosis

Protein kinase Cdelta (PKCdelta), a member of the novel PKC family, is emerging as a redox-sensitive kinase in various cell types. Oxidative stress activates the PKCdelta kinase by translocation, tyrosine phosphorylation, or proteolysis. During proteolysis, caspase-3 cleaves the native PKCdelta (72-74 kDa) into 41-kDa catalytically active and 38-kDa regulatory fragments to persistently activate the kinase. The proteolytic activation of PKCdelta plays a key role in promoting apoptotic cell death in various cell types, including neuronal cells. Attenuation of PKCdelta proteolytic activation by antioxidants suggests that the cellular redox status can influence activation of the proapoptotic kinase. PKCdelta may also amplify apoptotic signaling via positive feedback activation of the caspase cascade. Thus, the dual role of PKCdelta as a mediator and amplifier of apoptosis may be important in the pathogenesis of major neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and Huntington disease.     

Activation of protein kinase C delta by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2

Chronic inorganic manganese exposure causes selective toxicity to the nigrostriatal dopaminergic system, resulting in a Parkinsonian-like neurological condition known as Manganism. Apoptosis has been shown to occur in manganese-induced neurotoxicity; however, the down-stream cellular target of caspase-3 that contributes to DNA fragmentation is not established. Herein, we demonstrate that proteolytic activation of protein kinase Cdelta (PKCdelta) by caspase-3 plays a critical role in manganese-induced apoptotic cell death. Treatment of PC12 cells with manganese caused a sequential activation of mitochondrial-dependent pro-apoptotic events, including mitochondrial membrane depolarization, cytochrome c release, caspase-3 activation, and DNA fragmentation. Overexpression of Bcl-2 in PC12 cells remarkably attenuated each of these events, indicating that the mitochondrial-dependent apoptotic cascade contributes to manganese-induced apoptosis. Furthermore, PKCdelta was proteolytically cleaved by caspase-3, causing a persistent activation of the kinase. The manganese-induced proteolytic cleavage of PKCdelta was significantly blocked by Bcl-2-overexpression. Administration of active recombinant PKCdelta induced DNA fragmentation in PC12 cells, suggesting a pro-apoptotic role of PKCdelta. Furthermore, expression of catalytically inactive mutant PKCdelta(K376R) via a lentiviral gene delivery system effectively attenuated manganese-induced apoptosis. Together, these results suggest that the mitochondrial-dependent caspase cascade mediates apoptosis via proteolytic activation of PKCdelta in manganese-induced neurotoxicity.