Assessment of the potential in vivo genotoxicity of fluoranthene

Fluoranthene is a ubiquitous environmental pollutant. Althoughfluoranthene is mutagenic in bacterial and mammalian in vitrocell systems following metabolic activation by rat liver fraction,information on in vivo mutagenicity is lacking and studies ontumour initiating activity in mice are equivocal. In the presentstudy, the potential genetic hazard to man was assessed usingthe mouse bone marrow micronucleus and rat liver unscheduledDNA synthesis test systems. Fluoranthene did not show any evidenceof genotoxicity in either of the in vivo assays following acuteoral administration at levels of up to 2000 mg/kg b.w. ¹To whom correspondence should be addressed     

Y chromosome loss in esophageal carcinoma: An in situ hybridization study

Carcinoma of the esophagus shows a strong male predominance and other epidemiologic differences from cancers arising at other sites. In this study, the prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53 carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ hybridization of formalin-fixed paraffin-embedded tissue sections. Absence of the Y chromosome was defined as (1) negative staining for Y in neoplastic cells with positive staining for Y in immediately adjacent nonneoplastic epithelial and stromal cells, (2) positive staining of neoplastic cells with control probes for chromosomes X and 17, and (3) similar results at different stringencies and levels of protein digestion. According to these criteria, absence of the Y chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of 13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas arising in other sites. For the neoplasms examined, Y chromosome deletion was strongly and selectively associated with carcinomas, particularly adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y chromosome loss may be pathogenetically significant in these neoplasms. © 1993 Wiley-Liss, Inc.     

Gaucher disease: in vivo evidence for allele dose leading to neuronopathic and nonneuronopathic phenotypes

Gaucher disease, a common lysosomal storage disorder, is associated with mutations at the acid beta-glucosidase (GCase) locus. Two affected individuals are described to share a common mutant allele, but manifest different clinical categorical phenotypes. A 57-year-old female, with Gaucher disease type 1 and Cherokee ancestry, was homozygous for a rare mutant allele encoding Lys79Asn (K79N). A 2-year-old Caucasian male, with Gaucher disease type 3 and Cherokee ancestry, was a heteroallelic homozygote for this same allele (K79N) and a novel complex mutation (null allele). The shared alleles were identical as determined by complete gene sequencing, suggesting a founder effect. The discrepant phenotypes (types 1 and 3) in these two patients provide support for a threshold of residual activity necessary to "protect" the central nervous system (CNS) from the pathogenic effects of Gaucher disease, indicating an allele dose-effect. Designation of genotype associations with specific phenotypes must be assessed with this perspective.     

Disposition of the manchette in the normal equine spermatid

Bielanski and Kaczmarski (1979) reported the presence of microtubules in the neck region of mature stallion spermatozoa. It was hypothesized that these microtubules are derived from the manchette (a microtubular organelle present during spermiogenesis). In order to test this hypothesis, testes from 15 mature stallions were collected, perfused with 2% phosphatebuffered glutaraldehyde, and prepared for transmission electron microscopy. Spermatozoa from the caudae epididymides of each stallion were prepared in a similar manner. Spermiogenesis was observed in general, and the presence of a microtubular manchette was established in this species, juxtapositioned posterior to the nuclear ring and extending distally into the cytoplasmic collar which surrounds the prospective midpiece. Interlocking arms between the microtubules of the manchette were observed in transverse sections at all levels within the cytoplasmic collar before, during, and after caudal migration of the nuclear ring. Consequent to caudal migration of the nuclear ring and the annulus, as well as adluminal movement of the spermatid, the cytoplasmic collar was transformed into the residual cytoplasm. Within the residual cytoplasm, the manchette remained as a microtubular organelle which undergoes degeneration. The mature spermatozoa from the caudae epididymides of these stallions lacked the microtubules reported by Bielanski and Kaczmarski. The occurrence of such microtubules in the neck region of stallion spermatozoa is probably an abnormality.     

Homeostasis and the age-associated defect of CD4 T cells

Survival and homeostatic division of naive CD4 T cells is regulated by the cellular and non-cellular milieu and together these processes ensure that a population of naive CD4 T cells persists into old age. However, the naive CD4 T cells from aged animals show reduced IL-2 production, proliferation, helper function and effector generation and memory function. We explore here whether the age-related defects in naive CD4 T cells are due to the aged environment from which they come or to intrinsic defects that are caused by homeostasis and their long lifespan.     

Which treatment for whom for ADHD? Moderators of treatment response in the MTA

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.