Serotonin-depleting midbrain lesions fail to mitigate hyperphagia and obesity in the Zucker fatty rat

Previous research has shown that damage to the dorsal and median raphe nuclei of rats can impede the subsequent development of hypothalamic hyperphagia and obesity as well as impair the defense of established hypothalamic obesity in response to food deprivation. The present study sought to determine if raphe injury might alter the development of another form of obesity, namely that which occurs spontaneously in the Zucker fatty rat. Subjects were 20 obese females (fafa; mean weight of 200 g) and 20 lean littermate controls (FaFa females; mean weight of 150 g). Following 10 days of baseline intake and weight recordings, half of each group received radio-frequency heat lesions of the dorsal and median raphe nuclei while the other half received sham surgery. Except for a mild suppression of food intake and weight gain during the first few days after lesioning, raphe injury did not alter the hyperphagia or obesity shown by fatties over the 7 week ad lib feeding period studied. Additional 24-hr intake tests of varying sucrose and quinine solutions revealed reduced sucrose acceptance and enhanced quinine rejection by fatties much as has been seen in previous studies of hypothalamic obese rats. Terminal assays of forebrain monoamine levels confirmed that raphe lesions were effective in depleting serotonin (-71% compared to controls) without producing major changes in norepinephrine or dopamine (-14% and +2%, respectively). The inability of raphe lesions to mitigate this form of hyperphagia and obesity suggests that earlier observations of their attenuating effects on hypothalamic obesity were not due to non-specific impairments of behavioral or metabolic factors necessary to permit overeating and weight gain.     

Cystic lesions of the salivary glands: cytologic features in fine-needle aspiration biopsies

A variety of neoplastic and nonneoplastic lesions of the salivary glands have a predominantly cystic architecture. Fine-needle aspirates of these lesions yield watery or mucoid material, frequently of low cellularity. Such aspirates may be obtained from mucus retention cysts, lymphoepithelial cysts, cystadenomas, Warthin's tumors, cystic pleomorphic adenomas, low-grade mucoepidermoid carcinomas, cystadenocarcinomas, and examples of polycystic disease of the parotid gland. The cellular component within the fluid obtained from these lesions may be exceedingly scant or absent, making cytologic diagnosis difficult and, at times, impossible. We studied a series of 56 cystic lesions of the salivary glands, including 38 Warthin's tumors, 6 benign cysts, 2 lymphoepithelial cysts, 5 low-grade mucoepidermoid carcinomas, 1 cystic pleomorphic adenoma, 2 cystadenomas, and 2 cystadenocarcinomas. Careful attention to the cellular elements present often allowed definitive cytologic diagnosis, with an overall accuracy rate of 84%. The presence of atypical squamous metaplasia in oncocytic lesions was a significant cause of false-positive diagnoses of carcinoma (4 cases, 7%). Aspirates of low-grade mucoepidermoid carcinoma may contain no epithelial cells and result in false-negative diagnoses (1 case, 2%).     

Cytologic features of central giant-cell granuloma of the jaw

In this present series, we studied in detail the cytologic features of five histopathologically verified cases of central giant-cell granuloma (CGCG). All the patients in this series were female, with an age range of 11-60 years. There were three cases with involvement of the lower jaw and two cases had upper jaw involvement. Cytology smears showed dispersed single cells in the background. Nuclei of the individual cells were round to ovoid with fine chromatin and inconspicuous nucleoli. The cytoplasm of these cells was moderate in amount with indistinct cell borders. Many randomly scattered multinucleated giant cells with 10-20 nuclei were present in the background. Combination of clinical features, radiologic pictures, and cytologic features may be helpful for diagnosis of CGCG on fine-needle aspiration cytology.     

Aberrant retinal projections to midbrain targets mediate spared visual orienting function in hamsters with neonatal lesions of superior colliculus

Summary Rodents, cats, and most nonmammalian vertebrates with bilateral tectal deafferentation or ablation in adulthood are extremely deficient at orienting to visual stimuli; yet animals with neonatal lesions of superficial layers of the superior colliculus (SC) show partial sparing of this response, particularly for targets in the central visual field. In this study, we sought to determine whether these spared orienting abilities are mediated by aberrant retinal projections to the remaining intermediate layers of the SC, or whether visual cortex (VC) mechanisms or alternative behavioral strategies are responsible. Neonatal golden hamsters received either bilateral heat lesions of the SC (rlSC), or a heat lesion of the right SC and enucleation of the right eye (rSCrE). This latter procedure causes axons from the left eye to recross the tectal midline and terminate in the wrong (left) SC (Schneider 1973). As adults, both groups of hamsters were extremely deficient in visually guided approach to stationary targets, although rlSC-lesioned hamsters showed some sparing for central field targets and rSCrE-lesioned hamsters often made wrong-direction turns for targets in the left peripheral field. We then subjected both groups of neonatally lesioned hamsters to bilateral aspiration lesions of the VC. Retesting showed no change in visual orienting behavior as a result of the cortical lesions. Labeling of the optic tract with horseradish peroxidase (HRP) revealed abundant aberrant retinal projections to remaining intermediate layers of the SC and thalamic nucleus lateralis posterior (LP), as well as supernormal innervation of pretectal nuclei, the dorsal terminal nucleus of the accessory optic tract, and the ventral nucleus of the lateral geniculate body (LGv). We conclude that the spared visual orienting capabilities of hamsters with rlSC and rSCrE lesions are mediated by the aberrant midbrain projections, and that cortical mechanisms are not involved in spared visual orienting functions following these neonatal lesions.     

Inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action,on compound 48/80-induced gastric mucosal lesions in rats

We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on rat gastric mucosal lesions induced by compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of disodium cromoglycate (DSCG: a mast cell stabilizer), LY171883 (a peptidoleukotriene antagonist) and cimetidine (a histamine H₂ receptor antagonist). Subcutaneous administration of C48/80 (1 mg/kg) once daily for four consecutive days produced extensive gastric lesions in the fundic mucosa. DS-4574 (20, 50 and 100 mg/kg/day, oral) and DSCG (200 mg/kg/day, intraperitoneal) treatment markedly inhibited formation of these mucosal lesions, but LY171883 (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did not. Moreover, DS-4574 and DSCG significantly suppressed both hyperhistaminemia and histamine release from rat peritoneal mast cells induced by C48/80. These results indicate that the inhibitory effect of DS-4574 on gastric lesions induced by C48/80 may be related to its mast cell stabilizing action, but to neither its antisecretory nor its peptidoleukotriene antagonistic activity.     

Rostral midbrain lesions and copulatory behavior in male rats

Discrete electrolytic lesions were placed in the mesencephalic dorsal noradrenergic (DNE) bundle of 22 male Sprague-Dawley rats, and sham operations were performed on 14 control animals. Eight components of copulatory behavior were compared in 2 preoperative and 2 postoperative heterosexual mating tests. A significant postlesion decrease in the postejaculatory interval (PEI), number of intromissions, number of incomplete mounts and the ejaculation latency from the first intromission (ELI) occurred. Norepinephrine levels were significantly reduced in the hippocampus, amygdala and hypothalamus, but not in the preoptic area. The only statistically significant correlations between NE concentrations and behavior in the lesioned animals were negative (hippocampal NE with PEI and ELI). The results support the hypothesis that rostral midbrain lesions disinhibit some components of male rodent copulatory behavior, but suggest that a system or systems other than the DNE bundle may be responsible for this disinhibition.     

碱性成纤维细胞生长因子对卵巢癌CAOV3细胞cyclin D1及GADDl53表达的影响

目的:研究碱性成纤维细胞生长因子(bFGF)对人卵巢癌CAOV3细胞细胞周期调节蛋白cyclinD1及GADD153表达的影响,探讨bFGF促进人卵巢癌CAOV3细胞增殖、抑制凋亡的信号机制。方法:利用无血清饥饿诱导卵巢癌CAOV3细胞凋亡。分为对照组、bFGF组。分别应用MTT、流式细胞术、琼脂糖凝胶电泳观察25、50、75μg/L bFGF对CAOV3细胞增殖率、细胞周期及细胞凋亡的影响。利用Western blotting检测bFGF对CA-OV3细胞cyclin D1、GADD153以及转录因子(c-Fos、c-Jun)表达的影响。结果:与对照组相比,bFGF呈剂量依赖性加速CAOV3细胞细胞周期进程,促进细胞增殖,抑制饥饿诱导的凋亡(P<0.01);呈时间依赖性促进cyclinD1、c-Fos、c-Jun,抑制GADD153蛋白表达(P<0.01)。结论:bFGF可能通过上调cyclin D1、c-Fos、c-Jun,下调GADD153表达促进细胞增殖,抑制饥饿诱导的卵巢癌CAOV3细胞凋亡。     

Immunohistochemical analysis of 14-3-3 sigma and related proteins in hyperplastic and neoplastic breast lesions, with particular reference to early carcinogenesis

In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in breast carcinogenesis, we have studied the expression of 14-3-3sigma immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger protein (Efp) was also carried out. Immunohistochemically, expression of 14-3-3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERalpha. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested that it might be possible that CCHA is a precancerous lesion.     

Small-cell carcinoma of the ovary in peritoneal fluid

Two cases of small-cell carcinoma of the ovary in the ascitic fluid and peritoneal/pelvic washings of a 30- and 28-yr-old woman, respectively, are presented and discussed. Smear preparations from the ascitic fluid showed loose clusters and single malignant cells with scant cytoplasm and nuclei with smooth to irregular nuclear membranes, granular chromatin, and small nucleoli. In the second case peritoneal/pelvic washing specimens contained clusters and single malignant cells with a moderate amount of cytoplasm and nuclei with smooth nuclear membranes, granular, clumped chromatin, and prominent nucleoli. Histology confirmed the diagnosis of small-cell carcinoma of the ovary. These are the first reported cases of this rare ovarian neoplasm present on fluid cytology. Its differentiation from other small-cell neoplasms on peritoneal fluid cytology from young women is discussed. Diagn Cytopathol 1994; 11:266–270. © 1994 Wiley-Liss, Inc.     

Nucleus basalis lesions in neonate rats induce a selective cortical cholinergic hypofunction and cognitive deficits during adulthood

Summary Ibotenic acid was infused into the nucleus basalis magnocellularis (nBM) of 2-day old rats to eliminate immature cholinergic neurons before they develop functional synaptic connections in the neocortex. For bilaterally lesioned neonates, cognitive testing was initiated 2 months after lesioning and animals were sacrificed at 8 or 12 months of age. Lesioned animals exhibited a marked deficit in the retention of passive avoidance behavior, as well as in the acquisition of 2-way active avoidance behavior. Lesioned animals also made significantly more alternation errors than control animals in the Lashley III spatial maze and showed severe impairments in general learning, reference memory and working memory during 17-arm radial maze testing. For all 4 tasks, neonatally lesioned animals did not show any recovery to the performance level of control animals. Histological analysis of the subcortex from lesioned animals during adulthood revealed: (1) a substantial reduction in acetylcholinesterase-positive cells (presumably cholinergic) within the nucleus basalis, (2) decreased acetylcholinesterase staining in neocortex and (3) a gliosis essentially restricted to the globus pallidus. Surrounding brain regions were apparently not damaged as a direct result of excitotoxin infusion. Neurochemically, neonate nBM lesioning produced a long term cholinergic hypofunction as evidenced by significant reductions of 25% and 18% in frontal cortex chorine acetyltransferase (CAT) activity at 12 and 8 months of age, respectively. By contrast, prefrontal cortical concentrations of biogenic amines and their metabolites were unaffected, thus indicating a degree of neurochemical specificity for these neonatal nBM lesions. The persistant cortical cholinergic hypofunction in lesioned animals may be related to the long term deficits in learning/memory abilities that were also observed. It is suggested that neonatal nBM lesioning could provide a useful animal model for elucidating the plasticity of the developing brain after cortical anervation.