Cell origin of human adenovirus type 12-induced subcutaneous tumor in Syrian hamsters

Summary Single subcutaneous inoculation of human adenovirus type 12 (Ad. 12), 0.05–0.1 ml of 10^8.0 TCID50 HEK cells/0.1 ml, was made on the back of 0-day-old hamsters. In 21 of 25 hamsters (84.0%), multiple solid tumors developed close to the inoculation site within 3 months. No control hamsters developed tumors. Tumor histopathology revealed the characteristic Homer Wright rosettes of neuroblastoma. Ad. 12-specific tumor antigens were demonstable in both the primary and the cultured tumor cells by the hnmunofluorescein technique. Histochemical demonstration of cholinesterase and NADH oxidoreductase gave rise to a predominantly positive intracytoplasmic granule within the tumor cells. Electron microscopy showed remarkably iniform cell morphology: small, undifferentiated neuroblastic cells with poorly developed intracytoplasmic organelles; many possessed characteristic solitary cilia in a 9+0 tubules pattern. Intercellular junctions were poorly developed. Search for an incipient tumor cell aggregate by means of immunofluorescein T-antigen detection was carried out through a 240-h period following Ad. 12 inoculation. A sequential study in parallel with electron microscopic examination of the normal subcutaneous tissue proved that neuroblastic cells closely associated with the muscle spindle anlage could preferentially become the most sensitive target for Ad. 12 tumorigenesis.Part of this work presented at the 53rd National Meeting of the American Association of Neuropathologists in Chicago, June, 1977. Supported by PHS Grant EY-01667; by grants from Retina Research Foundation of Houston, TX; Fight for Sight, Inc., New York; Research to Prevent Blindness, Inc.; and by the Massachusetts Lions Eye Research Fund, Inc. Dr. Nakajima was a recipient to a Fight for Sight Grant-in-Aid Award     

A highly predictable animal model of retinoblastoma

Summary A new animal model of retinoblastoma was developed in newborn inbred CDF rats by intravitreous inoculation of retinal tumor cells (5×10⁴/5 l) derived from the cultured tumor cell line EXP-5. The retinal tumor from which the cell line originated was induced by a single intravitreous inoculation of human adenovirus serotype 12 (5 l of 10⁸ TCID 50/0.1 ml) in syngeneic rats. Within 1 month after intravitreous moculation of EXP-5 cells, a clinically recognizable ocular tumor was obtained in all 39 rats. Ad 12-specific T-antigens were demonstrated in the cultured tumor cells using immunofluorescent techniques. Morphologically these tumor cells closely resembled retinoblastuma, with poorly differentiated intracytoplasmic organelles, solitary cilia with a 9+0 tubule pattern, and abnormal nuclear membrane associated with a set of basal bodies. The significance of this highly manipulable retinal tumor cell line is the capability of providing a full-fledged intravitreous tumor in 1-month-old CDF rats, whose actual life span is known to be 42 months. Transplantable retinal tumors described to date are reviewed breifly and compared with the presently reported cell line.Supported by USPHS grants EY-CA01667, R01-EY-03171, and P30 EY-01784, by grants from the Retina Research Foundation, Houston, Texas, and by the Massachusetts Lions Eye Research Fund Inc.     

Cerebral lesions in rats with streptozotocin-induced diabetes

Summary We studied cerebral lesions in the streptozotocin-diabetic rat, an established model of diabetic retinopathy. A group of diabetic rats all had cerebral lesions, but showed no gross abnormalities of the brain or signs of effects on the central nervous system. Light and electron microscopy of horizontal brain sections stained by a variety of methods showed focal accumulation of collagen fibrils in the basement membranes of arteriole and capillary walls, slight degeneration of random neuronic cells (mainly in the brain stem), and no evidence of perivascular myelin pallor plaques. A marked tendency toward platelet aggregation, which leads to thrombosis, was also seen. There was no difference between results from rats killed 9 and 12 months after streptozotocin injection. The brain lesions bore a close resemblance to those seen in a nutritional encephalopathy known to be induced by a diet deficient in tocopherol and rich in oxidized oil, but differed from that encephalopathy in that the peculiar hypertrophic cerebral astroglia associated with diabetes resembled Alzheimer Type II astroglia. The differences between these cerebral astroglia and the retinal Müller cells may account for the difference in degree between the effects of diabetes on the brain and the retina.Part of this work was presented at the 55th National Meeting of American Association of Neuropathologists in Kansas City, June 1979This work was supported in part by PHS Research Grants R01 EY02062 and P30 EY01784 from the National Eye Institute, and by grants from Research to Prevent Blindness, Inc., New York, and the Massachusetts Lions Eye Research Fund, Inc.     

Psychophysiological symptoms in alcoholics and matched comparison persons

Respondents identified in a representative community sample as presumed alcoholics, persons with chronic stomach trouble, and persons with neither pathology were reinterviewed in the current study. Almost all psychophysiological symptoms were reported significantly more often by the alcoholics than by all adults in the earlier study. Reinterviews with alcoholics and matched controls confirmed the initial differences and revealed a decreasing order of symptom occurrence by alcoholics, persons with stomach trouble, and persons with neither pathology, respectively. The findings suggest that psychological impairment is associated to a marked degree with alcoholism, and to a smaller, although considerable, extent with stomach disorder.Haberman was formerly Associate Director of Research, National Council on Alcoholism, Inc., 2 East 103 Street, New York, N. Y.This study has been supported by the National Institute of Mental Health, U. S. Public Health Service Grant OM-664, and the Health Research Council of the City of New York Contract U-1254. The Master Sample Survey conducted by the Columbia University School of Public Health and Administrative Medicine was supported by the Health Research Council of the City of New York Contract U-1053. The psychological data in the Master Sample Survey were included there by B. P. Dohrenwend, Ph.D., and L. Kolb, M.D., under U. S. Public Health Service Grant OM-82.     

Psychiatrists' interest in community mental health centers

A postal inquiry among psychiatrists in New York State revealed a high level of interest in working in community mental health centers. The majority of those interested only wanted to work part-time in a center. The amount of time they would like to spend in the center and the types of work they would like to do were related to their present occupation and practice. Recruitment of personnel for these new services is very likely to aggravate the present staffing problems in state mental hospitals.This research was carried out while he was an Associate Research Scientist, New York State Mental Health Research Unit, Syracuse, New York. It was supported by the New York State Department of Mental Hygiene, Planning Commission. The author wishes to thank Dr. John Cumming and Dr. Elizabeth Tucker for their advice and assistance in carrying out the research on which this paper is based. He is also grateful to the clerical staff of the Mental Research Unit for their help in analyzing data and preparing reports.This paper was prepared before the appearance in print of Dr. F. R. Hassler's Psychiatric Manpower and Community Mental Health (Amer. J. Orthopsychiat., 1965,35, 695–706), which reports similar findings for a sample of Psychiatric Residents in the state of Massachusetts.     

Embryonal neuroepithelial tumors induced by human adenovirus type 12 in rodents

Summary Intracranial inoculation with human adenovirus type 12 (Ad12) induced tumors multicentrically in the brain and spinal cord of 37.2% of hamsters, 30.2% of mice, and in the brains of 91.0% of rats. Brain tumors developed preferentially at the olfactory bulb, lateral ventricular horns, tapetum region, and ventral and dorso-caudal aspects of the fourth ventricle. In the spinal cord, tumor developed on the dorsal aspect and, in hamsters, at the root of the cauda equina. Microtumors were found almost invariably in the subependymal areas and occasionally in the leptomeninges. The histological and ultrastructural features indicated extremely undifferentiated neoplasms analogous with the intraperitoneal tumors described in the companion report. Closely packed small polygonal or tadpole-shaped tumor cells resembled the subependymal cell remnants of normal perinatal brains. Divergent differentiation consisted in an intermingling of a fascicular or palisading arrangement of spongioblastic cells, of incomplete perivascular pseudorosettes and of neuroblastic (Homer Wright type) rosettes. Neither distinct neuronal nor neurogial fibrils were demonstrated. True ependymoblastomatous and medulloepitheliomatous rosettes were rarely encountered. These results indicate that Ad12-induced tumors in the central nervous system are of embryonal neuroectodermal origin and with limited differentiation, leading to divergent phenotypes corresponding to medulloblastoma, neuroblastoma, primitive spongioblastoma, ependymoblastoma and, rarely, medulloepithelioma.Supported by a Grant-in-Aid for Cancer Research from Ministry of Education, Science and Culture and a grant from the Tokyo Club, Japan     

ACT and Recovery: Integrating Evidence-Based Practice and Recovery Orientation on Assertive Community Treatment Teams

We examine whether Assertive Community Treatment (ACT), a widely implemented and rigorously studied practice, can successfully incorporate a recovery-oriented approach while continuing to retain program fidelity. We briefly review the effectiveness of ACT as an evidence-based practice, with a focus on adaptations to changing populations and contexts. We explore philosophical similarities and differences between ACT and recovery and examine how fidelity standards, a widely used indicator of how ACT teams operate, support or interfere with the adoption of a recovery-oriented practice. Finally, we provide recommendations on how best to incorporate a recovery orientation into existing ACT teams. Dr. Salyers is Co-Director of the ACT Center of Indiana, Associate Research Professor, Department of Psychology, IUPUI, and Research Scientist, VA HSR&D Center on Implementing Evidence-based Practice, Roudebush VAMC and Regenstrief Institute, Inc. Dr. Tsemberis is Founder and Executive Director of Pathways to Housing, Executive Director of the New York State Institute for ACT and Recovery Based Training, and Assistant Professor, Department of Psychiatry, NYU Medical Center.     

重组腺病毒介导P21WAF1/CIP1过量表达治疗人脑胶质瘤的实验研究

目的 研究基因转移P21^WAF1/CIP1过量表达对人脑胶质瘤细胞凋亡的影响和治疗作用。方法 本文构建缺陷型重组腺病毒载体：在CMV启支子控制下的人P21 cDNA（Ad-P21），其编码入P21蛋白。通过渡式细胞仪、RT－PCR进行P21表达检测；应用TUNEL法、免疫组化荧光显微镜和流式细胞仪进行相关凋亡检测、分析。结果 RT－PCR检测五株亲本胶质瘤细胞表达P21^WAF1/CIP1 cDNA，而流式细胞仪未检测到P21表达；Ad-P21转导的胶质瘤细胞株均过量表达P21；在体内外Ad-P21能诱导胶质细胞瘤向终末分化、凋亡或诱导炎症反应抑制肿瘤生长或消退。结论 基因转移P21^WAF1/CIP1为研究基因治疗恶性脑胶质瘤提供了有效的手段。     

The impact of client need scores on the allocation of resources for community mental health services in Massachusetts

The allocation of resources for community mental health services (CMHS) should rely on the assessment of client need. Recent emphasis on cost concerns has given further emphasis to allocation decisions. This paper examines the impact of client need scores in the allocation of resources for CMHS in Massachusetts. A mean per capita spending for CMHS was completed for the forty catchment areas in the state; and areas were categorized based on need score. Results of an analysis of variance indicated no significant difference in allocation between groups relative to client need. The impact of other variables on allocation was discussed.Dr. Pulice is currently a Research Scientist III, New York State Office of Mental Health, Albany, NY and a Lecturer in Psychiatry, Harvard University Medical School at Cambridge Hospital. Dr. Malkis is currently a Research Scientist III, New York State Office of Mental Health, Albany, NY. Address reprint requests to Dr. Pulice, Office of Mental Health, 44 Holland Avenue, 7th Floor, Albany, NY 12229.     

Embryonal neuroepithelial tumors induced by human adenovirus type 12 in rodents

Human adenovirus type 12 (Ad 12) was inoculated intraperitoneally, intrapleurally, intramuscularly or subcutaneously into newborn rodents. Tumors developed preferentially in the peritoneal cavities in 93.9% of the hamsters and 82.6% of the mice, but none in rats; in contrast to the high incidence of brain tumors in rats when the virus is injected intracranially. Serial section of peritoneal tissues and muscle of hamsters revealed multicentric microtumors with a close relation to peripheral nerve fibers 10 to 35 days after virus inoculation. Histologically, most tumors consisted of closely packed, irregularly arranged, small spindle or tadpole-shaped cells. However, divergent morphological differentiation showing palisade arrangement of spongioblastic tumor cells forming trabeculae, pseudorosettes with or without central blood vessel, and true rosettes of immature ependymal (ependymoblastic) or medulloepithelial type were observed. No further differentiation was detected on immunohistochemical or electron microscopical examination of the tumor cells. The immature neuroepithelial phenotypes and the early stages of tumor development indicated that Ad 12 had a definite affinity for embryonic neuroepithelial elements that have migrated along the peripheral nerve fibers of newborn hamsters and mice, perhaps with cells of neural crest origin, and had induced primitive neuroectodermal tumors as observed in human peripheral neuroepithelioma and medulloepithelioma.