Outbreak of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme in Curitiba,Brazil

Carbapenem-resistant Acinetobacter baumannii isolates were obtained from eight patients in two hospitals in Curitiba, Brazil. The isolates were multiresistant, belonged to a single strain, and produced the OXA-23 carbapenemase. Treatment options were limited, although the isolates were susceptible to polymyxin B in vitro. The strain contributed to the deaths of five patients.     

Chronic lymphocytic leukemia/small lymphocytic lymphoma associated with IgM paraprotein

We studied the clinicopathologic, immunophenotypic, and cytogenetic features of 26 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) associated with serum IgM paraprotein. The study group (16 men; 10 women; median age, 64 years; range, 40-82 years) represents approximately 2.5% of CLL/SLL cases at our institution. The paraprotein level ranged from 1 to 14 g/L (median, 4 g/L). Neoplasms in bone marrow were composed of small round lymphocytes arranged in nodular (n = 6), diffuse (n = 5), interstitial (n = 5), or mixed (n = 10) patterns. All cases were positive for monotypic surface immunoglobulin light chain, IgM/IgD, CD5, CD19, CD20, and CD23. CD11c (14/20 [70%]), CD79b (11/19 [58%]), FMC-7 (11/26 [42%]), CD22 (8/20 [40%]), and ZAP-70 (6/19 [32%]) were expressed in subsets of cases. Of 17 bone marrow specimens assessed by conventional cytogenetics, 6 were abnormal and 11 were diploid. The overall survival of this group (median follow-up, 24 months) was not significantly different from that for an age-, sex-and stage-matched group of 52 CLL/SLL patients without IgM paraprotein (P = .60). We conclude that CLL/SLL cases with serum IgM paraprotein are similar to other CLL/SLL cases in their clinicopathologic and immunophenotypic features.     

Afferent volleys in limb nerves influencing impulse discharges in cerebellar cortex I. In mossy fibers and granule cells

Summary This paper is the first of a series in which the processing of information in the cerebellum has been studied by investigating the effects that known inputs from limb nerves produce on the unitary spike potentials in the cerebellar cortex. These spikes have been recorded extracellularly at all depths along microelectrode tracks in the 5th, 4th and 3rd lobules of the anterior lobe in the lateral vermis or in the pars intermedia. These units have a background frequency of discharge, often very irregular, and computer averaging techniques have been employed in order to derive reliable information on the time course and intensity of the excitatory and/or inhibitory actions produced by the input against this background.Most of the spike responses recorded from the granular layer fall into two classes, one characteristic of impulses in mossy fibers, and the other of impulse discharges from granule cells. Both in the spontaneous background and in the response to afferent volleys in limb nerves the mossy fibers exhibit a performance in close accord with that described for the discharges up the spino-cerebellar tracts. The short latency of 6–9 msec for hindlimb stimuli and the high frequency burst response of 2–4 impulses are characteristic. The mossy fibers displayed a wide variety of responses to the wide range of testing inputs, there being various combinations of excitatory and inhibitory responses and also delayed excitatory actions, all of which must be assumed to be reflections of synaptic influences on the cells of origin of the mossy fibers in the spinal cord.Granule cells have a longer latency by several milliseconds, 9–20 msec for the hindlimb, and a slower frequency in their burst response which tended to be longer and more irregular. The small unitary spike potentials are more difficult to isolate. Also with repetitive stimulation granule cells are more readily depressed than are mossy fibers.Usually a granule cell exhibits a wider range of response to the various cutaneous and muscular afferents of a limb. Both mossy fibers and granule cells may display reciprocal responses to volleys from muscle nerves to antagonistic muscles. This attempt to define properties of the mossy fiber and granule cell spike potentials should help in their identification in future investigations.Post-Doctoral Fellow NINDS (1F2NB40,544101 NSRB).Post-Doctoral Fellow UHF Grant No. FTF-3-UB-70.     

Geminin regulates neuronal differentiation by antagonizing Brg1 activity

Precise control of cell proliferation and differentiation is critical for organogenesis. Geminin (Gem) has been proposed to link cell cycle exit and differentiation as a prodifferentiation factor and plays a role in neural cell fate acquisition. Here, we identified the SWI/SNF chromatin-remodeling protein Brg1 as an interacting partner of Gem. Brg1 has been implicated in cell cycle withdrawal and cellular differentiation. Surprisingly, we discovered that Gem antagonizes Brg1 activity during neurogenesis to maintain the undifferentiated cell state. Down-regulation of Gem expression normally precedes neuronal differentiation, and gain- and loss-of-function experiments in Xenopus embryos and mouse P19 cells demonstrated that Gem was essential to prevent premature neurogenesis. Misexpression of Gem also suppressed ectopic neurogenesis driven by Ngn and NeuroD. Gem's activity to block differentiation depended upon its ability to bind Brg1 and could be mediated by Gem's inhibition of proneural basic helix-loop-helix (bHLH)-Brg1 interactions required for bHLH target gene activation. Our data demonstrate a novel mechanism of Gem activity, through regulation of SWI/SNF chromatin-remodeling proteins, and indicate that Gem is an essential regulator of neurogenesis that can control the timing of neural progenitor differentiation and maintain the undifferentiated cell state.     

Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium

DNA-protein crosslinks (DPC) are a promising biomarker of exposure to hexavalent chromium, a known human carcinogen. Although trivalent chromium is considered to have much lower toxicity, the risk involved in chronic exposure is uncertain. DPC may be a useful tool in clarifying this risk, by signaling an exposure of body tissues to biologically active forms of chromium. DPC quantification was carried out in lymphocytes of a group of tannery workers exposed to trivalent chromium, a small group of manual metal arc stainless steel welders exposed to hexavalent chromium and a control group. This biomarker was compared with the frequency of micronuclei in cytokinesis blocked peripheral lymphocytes as a biomarker of cytogenetic lesions and total plasma and urine chromium levels as an index of exposure. The results indicate a significant increase in the formation of DPC in tannery workers compared with controls (0.88 +/- 0.19 versus 0.57 +/- 0.21%, P < 0.001, Mann-Whitney test) and an even higher level of DPC in welders (2.22 +/- 1.12%, P = 0.03). Tanners showed a significant increase in micronucleated cells compared with controls (6.35 +/- 2.94 versus 3.58 +/- 1.69 per thousand, P < 0.01), whereas in welders this increase was not significant (5.40 +/- 1.67 per thousand ). Urinary chromium was increased in both groups, with a greater increase observed in tanners compared with controls (2.63 +/- 1.62 versus 0.70 +/- 0.38 microg/g creatinine, P < 0.001) than in welders (1.90 +/- 0.37 microg/g creatinine, P < 0.005). Plasma chromium was also increased in both groups (tanners 2.43 +/- 2.11 microg/l, P < 0.001, welders 1.55 +/- 0.67 microg/l, P < 0.005 versus controls 0.41 +/- 0.11 microg/l). In summary, chronic occupational exposure to trivalent chromium can lead to a detectable increase in lymphocyte DNA damage which correlates with a significant exposure of the cells to the metal.     

Cyclin D1 expression in dysplastic nevi: an immunohistochemical study

OBJECTIVE: We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and malignant melanomas and reported that benign nevi maintain a zonal pattern of cyclin D1 expression, in contrast with malignant melanomas. Our aim was to extend those observations by examining cyclin D1 expression in dysplastic nevi. METHODS: Cyclin D1 overexpression in 23 dysplastic nevi was detected by an immunohistochemical technique. The extent of atypia of the nevi was graded as mild, moderate, or severe, using previously established criteria. RESULTS: Cyclin D1 overexpression in dysplastic nevi maintained a zonal pattern, similar to Spitz nevi. Cyclin D1 overexpression was greatest in the region of the epidermal-dermal junction and was significantly less prominent in the papillary and reticular dermis, suggesting that cyclin D1 expression is under cell control and correlates with maturation of nevus cells. Cyclin D1 overexpression also correlated with cytologic atypia, as dysplastic nevi with moderate or severe cytologic atypia contained a greater percentage of cyclin D1-positive cells than did nevi with mild atypia. Six dysplastic nevi with many cyclin D1--positive cells were assessed by fluorescence in situ hybridization studies using cyclin D1--specific and chromosome 11 centromeric probes. In all cases, there was no evidence of 11q13 translocation, amplification, or trisomy of chromosome 11. CONCLUSIONS: Cyclin D1 may be involved in the pathogenesis of dysplastic nevi. Cyclin D1 overexpression does not appear to be explained by cyclin D1 locus amplification or translocation in most cases, and it may be a result of other cell abnormalities that up-regulate the protein level of cyclin D1.     

Monitoring gp43 antigenemia in Paracoccidioidomycosis patients during therapy

Paracoccidioidomycosis (PCM) is a systemic fungal disease that is particularly important among individuals living and working in rural areas of endemicity in Latin America. Detection of anti-Paracoccidioides brasiliensis antibodies is of limited value due to false-negative results. Detection of P. brasiliensis-gp43 circulating antigen is a practical approach for a specific diagnosis of the disease. In a previous study we described an inhibition enzyme-linked immunosorbent assay able to detect the 43-kDa P. brasiliensis antigen in sera of 100% of patients with the acute form of PCM and in 95.31 and 100% of patients with the chronic multifocal and unifocal forms of PCM. To investigate its potential application for the follow-up of PCM patients during treatment, antigen levels were monitored at regular intervals for up 8 to 12 months in serum samples from 23 patients. The results showed that treatment with itraconazole resulted in decreasing levels of circulating gp43 that were correlated with the reduction of anti-gp43 antibodies. It was also observed that by the end of 12 months of treatment gp43 levels were <5 microg/ml in all patients.     

Fluorescent in situ hybridization in routinely processed bone marrow aspirate clot and core biopsy sections.

Fluorescent in situ hybridization (FISH) is a technique which complements conventional cytogenetic banding analysis by allowing the evaluation of cells in interphase as well as metaphase. This technique has been used to study air-dried peripheral blood and bone marrow aspirate smears. We have applied the FISH technique to study routinely processed sections of bone marrow aspirate clot and decalcified core biopsy specimens, fixed in either formalin or B5 and embedded in paraffin. We evaluated 28 specimens (8 aspirate clot and 20 core biopsy sections) for chromosome 8 copy number, studied previously by conventional cytogenetics, and found the following distribution: 15 with disomy, 11 with trisomy, and 2 with tetrasomy. Using a chromosome 8 alpha-satellite probe, we detected fluorescent hybridization signals in 18 of 28 specimens (64%); 6 of 8 (75%) aspirate clot sections, and 12 of 20 (60%) core biopsy sections. Ten of 13 (77%) B5-fixed and 8 of 15 (53%) formalin-fixed specimens had hybridizing signals. Specimen age was a significant factor; 10 of 11 (91%) specimens processed within the last 6 months showed signals, in contrast with 8 of 17 (47%) specimens older than 6 months. In the positive specimens, 200 cells were analyzed in areas where individual cells could be identified. In the disomic specimens, two signals per cell were seen in 34 to 66% of the cells. Rare cells (0-2%) with three signals were detected. In the trisomic specimens, three signals per cell were seen in 19 to 46% of the cells. In the tetrasomic specimens, four signals per cell were seen in 15 to 25% of the cells. We conclude that the FISH technique may be useful in the detection of numerical chromosomal abnormalities such as trisomy and tetrasomy 8 in routinely processed bone marrow aspirate clot and decalcified core biopsy sections.     

Malignant schwannoma with melanocytic and neuroepithelial differentiation in an infant with congenital giant melanocytic nevus: A complex neurocristopathy

We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409–429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy.