Organofluorine Hydrazone Derivatives as Multifunctional Anti-Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH₃)₂ residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC₅₀ values in the kinase assays.     

Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes

PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only. CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.     

Imprudent linking weaves a tangled Web

Hypertext linking is often embraced uncritically by Web authors eager to explore the power of hypertext without first considering its effects on their readers' comprehension. Hypertext linking is not a substitute for thought-we think with ideas, not with dissociated snippets of raw information. Even the most germane bits of information cannot become ideas, regardless of how cleverly they are stacked, listed or linked. Ideas define relevance, provide context and establish patterns. With patterns, most concepts become intelligible, and we need continuity and stability of theme and context to recognize patterns. So, like most powerful technologies, hypertext links are a mixed blessing. Used improperly, they can be detrimental to Web sites. “Loose links” can drive away an audience, dilute the site's message, confuse the reader with irrelevant digressions and become a continuing maintenance headache for site authors and Webmasters     

An epidemic of roller-blade injuries in children

Roller blading is a new and increasingly popular leisure activity in many countries. We reviewed 110 consecutive patients with roller-blade injuries between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and 27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no protective equipment on the limbs. Four months following injury 103 (93.6%) patients were fully recovered. The mean duration of school absence was 3 days. Subsequently 101 children returned to using roller-blades following injury. Seventy-three (66.3%) of these now use protective equipment. We found that injuries were unrelated to age or duration of roller-blading experience or to the brand-name of roller blades used, and that most of our patients wore no protective equipment at the time of injury.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts

The effects of arginine vasopressin (AVP) and oxytocin (OT) upon thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) release were studied in euthyroid rats. Intracerebroventricular (i.c.v.) infusion of AVP in doses of 0.5 ng or 5 ng led to significant increases in plasma levels of TSH as well as FT4 and FT3. The effects of OT injected i.c.v. in similar doses were not consistent (there was no parallel between the changes of respective hormones plasma levels). It may be concluded that vasopressin modulate the pituitary-thyroid system function; AVP is probably a physiological stimulator of TSH and thyroid hormones secretion.