Deformity correction and arthrodesis of the midfoot with a medial plate

Nine feet in eight patients undergoing tarsometatarsal (Lisfranc) or other midfoot arthrodeses for posttraumatic or degenerative arthritis were reviewed retrospectively. All patients were treated using a medial one-third tubular plate spanning the midfoot joints to be fused. Three feet underwent fusion in situ while six feet underwent correction of residual planus, planovalgus, or cavovarus deformity at the time of fusion. All patients achieved fusion within 12 weeks. A good or excellent result was achieved in seven of nine feet. There was no radiographic or clinical evidence of pseudarthrosis or medial hardware failure in any patient. No patient to date has required hardware removal for a painful or prominent implant. The talus first metatarsal angle was improved an average of 15.5 degrees in the lateral plane and 10 degrees in the AP plane in patients undergoing deformity correction. The technique of using a medial plate for midfoot arthrodesis allows for reliable fusion in patients who require salvage for midfoot arthritis. This technique also allows for correction of deformity in patients with residual midfoot deformity.     

The rap and hor proteins of Erwinia, Serratia and Yersinia: a novel subgroup in a growing superfamily of proteins regulating diverse physiological processes in bacterial pathogens

The enteric bacterium Serratia marcescens is an opportunistic human pathogen. The strain ATCC39006 makes the red pigment, prodigiosin (Pig), and the beta-lactam antibiotic carbapenem (Car). Mutants were isolated that were concomitantly defective for Pig and Car production. These mutants were found to have a mutation in the rap gene (Regulation of Antibiotic and Pigment). Sequence analysis of the rap gene revealed a predicted protein product showing strong homology to SlyA, originally thought to be a haemolytic virulence determinant in Salmonella typhimurium. Homologues of rap were detected in several bacterial genera, including Salmonella, Yersinia, Enterobacter, and species of the plant pathogen, Erwinia. The Erwinia hoeEr (homologue of rap) and the Yersinia horYe genes were also found to be very similar to rap and slyA. Marker exchange mutagenesis of horEr revealed that it encoded a regulatory protein controlling the production of antibiotic and exoenzyme virulence determinants in the phytopathogen, Erwinia carotovora subspecies carotovora. We have shown that these new homologues of SlyA form a highly conserved subgroup of a growing superfamily of bacterial regulatory proteins controlling diverse physiological processes in human, animal and plant pathogens.     

Beak and feather disease virus and porcine circovirus genomes: intermediates between the geminiviruses and plant circoviruses

Circoviruses are a diverse group of animal and plant pathogens with undefined relationships to one another but for their non-geminate, non-enveloped capsids and circular, single-stranded DNA genomes. The sequences of the beak and feather disease virus and porcine circovirus genomic DNAs are presented and analyzed in the context of the other members of the family. Sequence comparisons, inferred phylogenies, and geographic occurrence suggest that the ambisense circoviruses, particularly the beak and feather disease virus, represent an evolutionary link between the geminiviruses and the plant circoviruses. We propose that the family members be reclassified into three groups: The family Circoviridae consists of the animal pathogens (beak and feather disease virus and porcine circovirus) that possess ambisense genomes with striking similarities to the geminiviruses. The BBTV-like viruses include the plant pathogens (coconut foliar decay virus, banana bunchy top virus, subterranean clover stunt virus) with a geminivirus-like stem-loop element in their DNAs, and single to multiple component genomes. The chicken anemia virus is an unassigned virus possessing unique characteristics bearing little similarity to the other ssDNA viruses.     

Studies on the role of platelet eicosanoid metabolism and integrin alpha IIb beta 3 in tumor-cell-induced platelet aggregation

Platelet eicosanoid metabolism resulting from tumor-cell-induced platelet aggregation (TCIPA) was examined in a homologous in vitro system. Rat Walker 256 carcinosarcoma cells induced the aggregation of rat platelets via a thrombin-dependent mechanism with concomitant production of eicosanoid metabolites (e.g., 12-HETE, TXA2). TCIPA was dependent on the concentration of tumor cells inducing aggregation, as well as cyclooxygenase and lipoxygenase products. Cyclooxygenase inhibitors, but not lipoxygenase inhibitors, blocked platelet aggregation induced in vitro by a low concentration of agonist. At a high agonist concentration, neither cyclooxygenase nor lipoxygenase inhibitors alone affected platelet aggregation; however, the combined inhibition of both the cyclooxygenase and lipoxygenase pathways resulted in subsequent inhibition of platelet aggregation regardless of agonist concentration. The extent of platelet TXA2 and 12-HETE biosynthesis was likewise dependent on and correlated with agonist concentration. The inhibitors used in this study did not significantly inhibit protein kinase C activity at the doses tested. Platelet surface glycoprotein alpha IIb beta 3 play an important role in platelet aggregation. The effect of platelet cyclooxygenase and lipoxygenase inhibition in regulating alpha IIb beta 3 surface expression was examined by flow cytometric analysis. Thrombin stimulation of washed rat platelets resulted in significantly increased surface expression of platelet alpha IIb beta 3 integrin complex. The enhanced surface expression was not inhibited by a cyclooxygenase inhibitor (aspirin), a thromboxane synthase inhibitor (CGS-14854) or a thromboxane receptor antagonist (SQ 29,548), nor was it stimulated by a thromboxane A2 mimic (pinane-thromboxane A2). However, alpha IIb beta 3 expression was blocked by lipoxygenase inhibition and stereospecifically increased by the platelet lipoxygenase metabolite 12(S)-HETE. These results suggest that both the platelet lipoxygenase and cyclooxygenase pathways are important for TCIPA but that different mechanisms of action are involved.     

Papillary squamous cell carcinoma of the uterine cervix: report of a case with HPV 16 DNA and brief review

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is a rare variant of squamous cell carcinoma (SCC). It is characterized by a papillary architecture and markedly atypical epithelium. Invasion and metastasis have been reported. We report a case of PSCC in a 72-year-old woman who subsequently tested positive for HPV 16. To our knowledge, this is the first report of HPV typing in a case of PSCC. Our finding of a high-risk HPV type in PSCC may help explain why PSCC has been reported to have a clinical course similar to that of nonpapillary SCC.     

The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat

BACKGROUND: Stimuli that stress cells, including inflammatory cytokines, ultra-violet irradiation, DNA-damaging chemotherapeutic drugs and heat shock, stimulate a recently identified cytoplasmic signaling system that is structurally related to the mitogen-activated protein kinase pathway. This pathway consists of a cascade of protein kinases including stress-activated protein kinase (SAPK), also termed Jun N-terminal kinase (JNK), and two kinases that activate it, MEKK and SEK/MKK4. Despite rapid progress in delineating the components of this pathway, the cellular consequence of its activation remains to be defined. RESULTS: We have screened cells for defects in SAPK signaling and identified a cell line, previously characterized for its thermotolerance properties, as being more refractive to SAPK activation induced by heat stress than its thermosensitive parental line. Stable expression of dominant inhibiting SEK mutants in thermosensitive parental cells specifically and effectively blocked SAPK activation after heat shock. These lines also became markedly resistant to the cytocidal effects of thermal stress, confirming the phenotype of the thermotolerant line. These cell lines defective in SAPK activation were also resistant to the lethal effects of the DNA-damaging drug cis-platinum. CONCLUSIONS: Experimentally induced stable blockade of SAPK activation in cells with normal thermosensitivity is sufficient to confer resistance to cell death induced by diverse stimuli including heat and the chemotherapeutic agent cis-platinum. These results suggest that activation of the SAPK pathway by diverse cell stressors plays a critical part in mediating the toxicity of these treatments and inducing cell death. SAPK activation in this context could broadly influence cellular response to stress, modulate apoptosis during development or determine the clinical response of tumor cells to cytotoxic therapies.     

Neuronal Ca2+ sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin and PC12 cells and regulates neurosecretion from dense-core granules

Neuronal Ca2+ sensor 1 (NCS-1) is the mammalian homologue of the Ca2+-binding protein frequenin previously implicated in regulation of neurotransmission in Drosophila (Pongs, O., Lindemeier, J., Zhu, X. R., Theil, T., Endelkamp, D., Krah-Jentgens, I., Lambrecht, H.-G., Koch, K. W., Schwemer, J., Rivosecchi, R., Mallart, A., Galceran, J. , Canal, I., Barbas, J. A., and Ferrus, A. (1993) Neuron 11, 15-28). NCS-1 has been considered to be expressed only in neurons, but we show that NCS-1 expression can be detected in bovine adrenal chromaffin and PC12 cells, two widely studied model neuroendocrine cells. NCS-1 was present in both cytosolic and membrane fractions including purified chromaffin granules, and in immunofluorescence, its distribution overlapped with peripheral punctate staining seen with the synaptic-like microvesicle marker synaptophysin in PC12 cells. The possible functional role of NCS-1 in exocytosis of dense-core granules was tested using transient transfection in PC12 cells and assay of co-transfected growth hormone (GH) release. Overexpression of NCS-1 increased evoked GH release in intact cells in response to ATP. No effect of overexpression was seen on GH release because of Ca2+ in permeabilized cells suggesting that NCS-1 may have a regulatory but not direct role in neurosecretion.