Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions.

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis, apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining coordinated gene expression profiles but are also highly effective for molecularly "fingerprinting" diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious disease pathogenesis.

Transcriptional regulation in the immune system: all roads lead to AP-1.

The mechanisms regulating the development and function of the immune system are diverse and complicated. The signaling pathways and target genes that become activated upon cell-surface stimulation are currently being defined, and transcription factor activator protein 1 (AP-1) is proving to be an important regulator of nuclear gene expression in leukocytes. In vitro and in vivo studies have demonstrated that AP-1 expression is induced after a diverse range of stimuli and that AP-1 contributes to the regulation of a large number of genes. In this review we will examine the role of AP-1 during leukocyte activation and differentiation in the immune system.

Effects of basic fibroblast growth factor on in vivo cerebral tumorigenesis in rats.

OBJECTIVE: In vitro evidence suggests that basic fibroblast growth factor (bFGF) promotes tumor cell proliferation and angiogenesis. In this study, we evaluated the early and delayed effects of recombinant human bFGF on the early and late phases of in vivo, in situ tumorigenesis in rats. METHODS: Brain tumors were induced by transplacentally exposing fetal rats to N-nitrosoethylurea on Day 17 of pregnancy. On postnatal (PN) Day 60 or 90, N-nitrosoethylurea-exposed rats underwent stereotactic intraventricular implantation of Gelfoam saturated with bFGF (60 micrograms) or vehicle; the rats were killed 4 days (early group) or 30 days (delayed group) later. The early and delayed effects of bFGF on the early phase of tumorigenesis (PN Day 60) were evaluated in 14 and 10 rats, respectively; early and delayed effects on the late phase of tumorigenesis (PN Day 90) were evaluated in 12 rats each. RESULTS: Histological examination 30 days after implantation showed a significantly higher tumor rate in rats that had been treated with bFGF on PN Day 90, compared with vehicle-treated control rats (P < 0.05); furthermore, in the bFGF-treated animals there was significantly greater intratumoral and periventricular glial fibrillary acidic protein expression, as determined immunohistochemically. Increased vascularity in the tumor ipsilateral to the implant was found in 2 of 14 rats that had been treated with bFGF on PN Day 60. CONCLUSION: These findings support in vitro evidence that bFGF and its receptor complex are implicated in the genesis and progression of N-nitrosoethylurea-induced brain tumors in this animal model.

Cervical epidural hematoma after chiropractic manipulation in a healthy young woman: case report.

OBJECTIVE AND IMPORTANCE: Posttraumatic spinal epidural hematoma is an uncommon entity. We present the first report of spinal epidural hematoma occurring after chiropractic manipulation in a healthy young adult without preexisting cervical disease or any obvious predisposing factors. CLINICAL PRESENTATION: The patient presented with radicular and myelopathic symptoms that developed 15 minutes after chiropractic manipulation. Computed tomography and magnetic resonance imaging were performed. They revealed a cervical epidural hematoma. INTERVENTION: The hematoma was evacuated, and all of the patient's neurological symptoms improved over the course of the next 3 days. CONCLUSION: Although cervical spinal epidural hematoma is a rare clinical entity, it must be considered in patients with pain or neurological deficit after cervical trauma.

Predictive value of balloon test occlusion of the internal carotid artery.

Balloon test occlusion (BTO) of the internal carotid artery (ICA) is used in conjunction with single-photon emission computed tomography (SPECT) imaging to assess the cerebrovascular collateral reserve prior to surgical manipulation of the artery. The present report reviews 56 consecutive patients with tumors or vascular lesions at the base of the skull who underwent BTO and subsequent treatment on that basis within a 3-year period. Four patients underwent carotid sacrifice, since they tolerated the BTO and had normal SPECT imaging. Postoperatively, one patient had patchy infarcts in the frontal lobe, another a middle cerebral artery territory infarction, a third had a lacunar infarct, and the fourth had an impending stroke and was treated with an emergent revascularization procedure. There were 15 patients who underwent saphenous vein bypass grafting, of these there were three graft occlusions, one of which resulted in an infarction. There were two other infarctions due to technical difficulties, one being related to the revascularization procedure. Based on these results, we suggest that passing BTO with a normal SPECT study does not necessarily indicate that the patient is immune to stroke following carotid sacrifice. Revascularization should be considered, when ICA sacrifice is deemed necessary to treat the pathologic condition adequately, to minimize the likelihood of a stroke.

Neurological recovery after cranioplasty.

A patient who sustained a gunshot wound to the head was successfully treated with acute neurosurgical intervention. Six months after the injury, cranioplasty was used to repair a large skull defect. After cranioplasty, the patient developed significant improvement in motor function in his left upper extremity, which had been plegic after his injury. Although the mechanism of neurological recovery after cranioplasty is controversial, the occurrence of such improvement may be a sufficient indication for cranioplasty in certain patients.