Symptom formation as an expression of disordered information processing in schizophrenic children

The possible mechanisms that underlie symptom formation in childhood schizophrenia are discussed. A body of research evidence has been reviewed in which dissociation in relation to information processing was examined for its possible consequence in the formation and expression of symptomatology. Schizophrenic children have been found to exhibit dissociation of integrative processes among the sense systems at a level which is several years below normal expectation, and they usually fail to improve as age increases. The clinical manifestations of schizophrenia are considered to be the consequence of the conflict, distortion, and deprivation that derive from failure in information processing. These consequences can best be understood within a developmental framework which encompasses the different age-stages of function. This approach to the understanding of symptom formation is discussed in relationship to other evidence which suggests that primary neurological abnormality is present in schizophrenic children. Thus the identification of abnormality of intersensory integrative function may increase our understanding of etiology as well as of the mechanisms of symptom formation in schizophrenic children.     

Adrenal cyst

Three cases of adrenal cyst are presented with reference to cause, diagnosis, and treatment.     

Inhibition of DNA Synthesis in Animal Cells by Ethylene Diamine Tetraacetate, and Its Reversal by Zinc

During an investigation of the role of ions in growth regulation, it was found that ethylene diamine tetraacetate (EDTA) inhibits DNA synthesis about 10-fold in cultures of chick embryo cells, while ethylene glycol bis(beta-amino ethyl ether)-N,N'-tetraacetate has no effect. RNA synthesis is only slightly inhibited by EDTA, and protein synthesis is unaffected. EDTA is inhibitory to DNA synthesis at a concentration much lower than that of either Ca(++) or Mg(++) present in the growth medium. The inhibition is prevented by the addition of Zn(++) at a much lower concentration than that of the EDTA. Other metal ions are ineffective. The inhibition of DNA synthesis only becomes apparent after more than 6 hr of incubation with EDTA, and descends to its final level by 15 hr. Complete restoration of the original rate of DNA synthesis is achieved within 8-10 hr by the addition of Zn(++). The low rate of DNA synthesis that occurs in a density-inhibited culture, is refractory to further inhibition by EDTA. Rous sarcoma cells are less sensitive to inhibition by EDTA than normal cells, but the sensitivity of both is increased by reducing the concentration of Ca(++) in the medium. DNA synthesis in mouse 3T3 cells is also inhibited by EDTA. It is concluded that Zn(++) is a continuing requirement for DNA synthesis in cultured vertebrate cells, and it is suggested that the availability of Zn(++) within the cell may play a role in the regulation of cell multiplication.     

Sigmoidovaginal and cecovaginal fistula as a complication of peridiverticulitis: Report of eight cases

Diseases of the Colon &; Rectum -     

Squamous-cell carcinoma of the anus

Summary The records of 102 patients with squamous-cell carcinoma of the anus are analyzed. A protocol for the evaluation and management of this lesion is outlined. Read before the meeting of the Pennsylvania State Medical Society, Host Farm, Lancaster, Pennsylvania, November 18, 1970.     

Operative Cholangiography

Operative cholangiography was first used by Mirizzi in 1932, but still has not gained general acceptance by surgeons. With these facts in mind, this article reviews 31 cholecystectomies, 20 having been performed by the author, in which operative cholangiography was used, and discusses its technique, difficulties and results.     

Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia

KLF4/GKLF normally functions in differentiating epithelial cells, but also acts as a transforming oncogene in vitro. To examine the role of this zinc finger protein in skin, we expressed the wild-type human allele from inducible and constitutive promoters. When induced in basal keratinocytes, KLF4 rapidly abolished the distinctive properties of basal and parabasal epithelial cells. KLF4 caused a transitory apoptotic response and the skin progressed through phases of hyperplasia and dysplasia. By 6 weeks, lesions exhibited nuclear KLF4 and other morphologic and molecular similarities to squamous cell carcinoma in situ. p53 determined the patch size sufficient to establish lesions, as induction in a mosaic pattern produced skin lesions only when p53 was deficient. Compared with p53 wild-type animals, p53 hemizygous animals had early onset of lesions and a pronounced fibrovascular response that included outgrowth of subcutaneous sarcoma. A KLF4-estrogen receptor fusion protein showed tamoxifen-dependent nuclear localization and conditional transformation in vitro. The results suggest that KLF4 can function in the nucleus to induce squamous epithelial dysplasia, and indicate roles for p53 and epithelial-mesenchymal signaling in these early neoplastic lesions.     

Growth suppression induced by the TRC8 hereditary kidney cancer gene is dependent upon JAB1/CSN5

TRC8 encodes an E3-ubiquitin ligase disrupted in a family with hereditary renal cell carcinoma (RCC). We previously reported that Drosophila Trc8 (DTrc8) overexpression inhibits growth and that human and fly proteins interact with with the COP9 signalosome (CSN) subunit JAB1/CSN5. However, further mechanistic evidence linking DTrc8 growth suppression to CSN5 was lacking. Here, we show that haploinsufficiency of CSN5, or a T100I point mutation (CSN5(3)), relieved growth suppression by DTrc8, whereas CSN5(1) (E160V) and CSN5(2) (G147D) mutations had no effect. The strength of yeast two-hybrid interactions between DTrc8 and CSN5 were in complete agreement with the observed phenotypes. DTrc8 overexpression resulted in elevated levels of CSN5 and CSN7, but had no effect on NEDD8-modified Cul-1. In contrast to CSN5, heterozygosity for CSN4null had no effect on the DTrc8 phenotype. We also looked for genetic interactions between DTrc8 and other MPN domain proteins in the CSN and 26S proteasome lid. CSN6 haploinsufficiency restored growth, whereas reduction of proteasome subunits RPN8 or RPN11 had no effect. DTrc8 expression increased the level of digitonin-extractable CSN complex, consistent with elevated levels of CSN5 and 7. Our genetic results confirm that DTrc8-induced growth suppression is CSN5 (and CSN6) dependent. While there was no obvious influence on CSN deneddylation activity, the increase in CSN subunits and holocomplex suggests that TRC8 modulates signalosome levels or compartmentalization.