Disk susceptibility of ofloxacin, a new carboxyquinolone.

Ofloxacin, a fluorinated carboxyquinolone, was tested against 485 clinical isolates, and the MICs and disk inhibitory zones were correlated. A critical zone of greater than or equal to 19 mm and an MIC of less than or equal to 2 micrograms/ml indicate susceptibility. An MIC of 4 micrograms/ml and a zone size of 16 to 18 mm is intermediate, and an MIC of greater than or equal to 8 micrograms/ml with a zone size of less than 15 mm indicates resistance. Alternatively, organisms inhibited by an MIC of less than or equal to 4 micrograms/ml with a critical zone diameter of greater than or equal to 15 mm could be considered susceptible. By either of these criteria, major errors in judging susceptibility or resistance are less than 1%.     

Aromatic alkylamine N-acetyltransferase in regional tissues of developing rat brain

The specific activities of N-acetyltransferase (EC 2.3.1.5) were examined in several regions of rat brain of both sexes at various times after birth. The enzyme activity increased with development in whole brain, hippocampus, midbrain, cerebellum and the remainder of brain, peaking around 36 days of age. Lineweaver-Burk plots indicated linear kinetics for N-acetyltransferase in dialyzed supernatant and ammonium sulfate precipitates from the newborn rat brain, whereas enzyme preparation further purified by Bio Gel yielded biphasic kinetics. These data remain consistent with the possibility that there are two forms of N-acetyltransferase in rat brain even from birth.     

Relapsing polychondritis studied by computed tomography

Computed tomographic findings in a patient with relapsing polychondritis are described. Collapse of the cartilage of the nose and calcification in cartilages of the ears were clearly demonstrated. CT scanning was also helpful in evaluating the tracheobronchial tree for airway compromise, which could prove fatal in this condition.     

Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population

Functional and genomic approaches can be integrated to screen efficiently for pathogenic alleles in founder populations. We applied such approaches to analysis of the cancer-associated cell cycle regulator CHEK2 in the Ashkenazi Jewish population. We first identified two extended haplotypes at CHEK2 that co-segregated with breast cancer in high-risk families. We sequenced CHEK2 in a case representing each haplotype and discovered two novel amino acid substitutions, CHEK2.S428F in the kinase domain and CHEK2.P85L in the N-terminal region. To assay these alleles for loss of CHEK2 function, we tested their capacity to complement Rad53 deletion in Saccharomyces cerevisiae. CHEK2.S428F failed to complement Rad53 and thus largely abrogates normal CHEK2 function, whereas CHEK2.P85L complemented Rad53 as well as did wild-type CHEK2. Epidemiologic analyses were concordant with the functional tests. Frequencies of CHEK2.S428F heterozygotes were 2.88% (47/1632) among female breast cancer patients not selected for family history or age at diagnosis and 1.37% (23/1673) among controls (OR=2.13, 95% CI [1.26, 3.69], P=0.004), whereas frequencies of CHEK2.P85L were 0.92% among cases and 0.83% among controls. On the basis of the experience of mothers, sisters and daughters of probands, breast cancer risk due to CHEK2.S428F was estimated as 0.17 (+/-0.08) by age 60. We conclude that CHEK2.S428F increases breast cancer risk approximately 2-fold among Ashkenazi Jewish women, whereas CHEK2.P85L is a neutral allele. In general, these results suggest that selecting probands with extended haplotypes that co-segregate with disease can improve the efficiency of resequencing efforts and that quantitative complementation tests in yeast can be used to evaluate variants in genes with highly conserved function.     

Phosphorylation state-specific antibodies: applications in investigative and diagnostic pathology

Until recently, the investigation of protein phosphorylation was limited to biochemical studies of enzyme activities in homogenized tissues. The availability of hundreds of phosphorylation state-specific antibodies (PSSAs) now makes possible the study of protein phosphorylation in situ, and is opening many exciting opportunities in investigative and diagnostic pathology. This review illustrates the power of PSSAs, especially in immunohistochemical applications to human disease and animal models. Technical considerations, including antibody specificity and lability of phosphoepitopes, are covered, along with potential pitfalls, illustrated by a case study. In the arena of oncology, PSSAs may prove especially valuable in directly demonstrating the efficacy of chemotherapies targeted at protein kinase cascades. Novel applications of PSSAs are also beginning to reveal molecular mechanisms of inflammatory, degenerative, and toxin-induced diseases.     

Neonatal lingual choristoma with respiratory and gastric epithelium

Lingual choristomas are rare entities that typically present as benign cystic masses that are lined with a variety of heterotopic epithelia. Lingual choristomas that are lined with respiratory and/or gastric or intestinal mucosa are believed to derive from pluripotential cells of the embryonic foregut. We describe a neonate with a lingual cyst that was lined predominantly by respiratory epithelium and focally by gastric foveolar epithelium, and we review the terminology, etiology, and management of lingual cysts of presumed foregut origin.     

Children’s mental health after disasters: The impact of the world trade center attack

This paper summarizes the results of systematic studies published in peer-reviewed journals from 1999 to 2002 addressing post-traumatic stress reactions in children after mass disasters. Children’s post-traumatic reactions are considered in five different contexts—natural disasters, large-scale human-induced accidents, spree shootings, war, and terrorism. Association of these reactions with gender and age, as well as longitudinal course, is addressed. Other post-traumatic reactions in children after a mass disaster, as well as the comorbidity of these with stress reactions, are reported. With this as background, the most relevant epidemiologic investigations conducted after the World Trade Center attacks are then described. It is expected that new knowledge in the area of children’s post-traumatic reactions to disasters will result from the research initiatives launched after September 11, 2001.