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Biomedical subjects

Rajan Jain

Publications and source records attributed to Rajan Jain.

13 recordsLinked to original sources

Kruppel-like factor 2 inhibits protease activated receptor-1 expression and thrombin-mediated endothelial activation.

OBJECTIVE: The serine protease thrombin can dramatically alter endothelial gene expression in a manner that confers a proinflammatory phenotype. Recent studies have identified the Kruppel-like factor 2 (KLF2) as a critical regulator of endothelial gene expression. Herein, we provide evidence that KLF2 inhibits thrombin-mediated endothelial activation via alterations in expression of its principal receptor protease-activated receptor-1 (PAR-1). METHODS AND RESULTS: Forced expression of KLF2 in human umbilical vein endothelial cells potently inhibited the ability of thrombin to induce multiple prothrombotic factors (tissue factor, CD40L, plasminogen activator inhibitor-1), cytokines/chemokines (eg, monocyte chemotactic protein-1, interleukin-6 [IL-6], IL-8), and matrix degrading enzymes (eg, matrix metalloproteinases 1, 2, and 9). Mechanistically, KLF2 inhibits PAR-1 expression and, as a consequence, thrombin-mediated nuclear factor kappaB (NF-kappaB) nuclear accumulation and DNA binding. Conversely, small interfering RNA-mediated knockdown of KLF2 increases PAR-1 expression and thrombin-mediated induction of NF-kappaB activation. CONCLUSIONS: These studies identify KLF2 as a novel regulator of PAR-1 expression and thrombin action in endothelial cells.

Cells, Cultured↗

Direct infiltration of brainstem glioma along the cranial nerves.

The authors describe a case of a low-grade brainstem glioma extending along the cranial nerves without any evidence of leptomeningeal spread. The tumor extended directly along the VII-VIIIth cranial nerve complex and also along the trigeminal nerve, which is quite an unusual characteristic of the glial tumors.

Adult↗

Radiation-induced cavernomas of the brain.

The purpose of this report is to add support to the growing literature that there is a correlation between radiation and cavernomas of the brain, particularly if the radiation is received in childhood, as well as to increase awareness of this correlation in the radiology community. Retrospective review of our experience returned five patients who received radiation therapy while they were children and developed cavernomas in the irradiated tissues 3-41 years later. Cavernomas should be considered in the differential diagnosis of a hemorrhagic lesion in any patient who has received previous CNS radiation, particularly if he or she underwent radiation therapy in childhood.

Adolescent↗

Cerebral perfusion CT: technique and clinical applications.

Perfusion computed tomography (CT) is a relatively new technique that allows rapid qualitative and quantitative evaluation of cerebral perfusion by generating maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The technique is based on the central volume principle (CBF = CBV/MTT) and requires the use of commercially available software employing complex deconvolution algorithms to produce the perfusion maps. Some controversies exist regarding this technique, including which artery to use as input vessel, the accuracy of quantitative results, and the reproducibility of results. Despite these controversies, perfusion CT has been found to be useful for noninvasive diagnosis of cerebral ischemia and infarction and for evaluation of vasospasm after subarachnoid hemorrhage. Perfusion CT has also been used for assessment of cerebrovascular reserve by using acetazolamide challenge in patients with intracranial vascular stenoses who are potential candidates for bypass surgery or neuroendovascular treatment, for the evaluation of patients undergoing temporary balloon occlusion to assess collateral flow and cerebrovascular reserve, and for the assessment of microvascular permeability in patients with intracranial neoplasms. This article is a review of the technique, clinical applications, and controversies surrounding perfusion CT.

Blood Volume↗

Carotid perfusion CT with balloon occlusion and acetazolamide challenge test: feasibility.

Carotid balloon test occlusion (BTO) is used to assess the collateral circulation and cerebrovascular reserve in patients in whom carotid artery occlusion is contemplated. Eight patients in whom the test was successful were evaluated with perfusion computed tomography (CT) in the resting state and after acetazolamide challenge. Three of the patients showed symmetric blood flow and normal response to acetazolamide. One of them underwent permanent carotid occlusion and did not develop any delayed ischemic stroke. The remaining five patients showed asymmetric blood flow. One of them had markedly low blood flow and abnormal response to acetazolamide. The patient developed ipsilateral hemispheric stroke following permanent carotid occlusion after the superficial temporal artery to middle cerebral artery bypass graft occluded. In the other four patients, the steal phenomenon was seen in ipsilateral and contralateral hemispheres. Although definitive quantitative values for perfusion CT are not yet standardized, it may be feasible to predict that the patients with symmetric blood flow and normal acetazolamide-enhanced challenge test results will do well after permanent carotid occlusion. Patients with asymmetric blood flow and abnormal response to the acetazolamide challenge test may require a revascularization procedure to protect them from delayed ischemic stroke.

Acetazolamide↗

Management of patients with stunned myocardium associated with subarachnoid hemorrhage.

Cardiac complications are well known after aneurysmal subarachnoid hemorrhage. Electrocardiographic changes occur in 50% to 100% of such cases. Arrhythmias, left ventricular dysfunction, and frank myocardial infarction are infrequently observed. Myocardial infarction must be differentiated from neurogenic stunned myocardium, which is a reversible condition. From 1996 to 2001, 105 patients with aneurysmal subarachnoid hemorrhage underwent endovascular treatment at the University of Michigan. Of these, four patients with no history of cardiac disease experienced cardiac failure related to neurogenic stunned myocardium. All had signs of left ventricular dysfunction, electrocardiographic changes, and elevated cardiac enzymes. Three had pulmonary edema at presentation. All were diagnosed with myocardial infarction. One underwent coronary angiography, which was normal. All were considered poor surgical candidates and underwent endovascular treatment of the aneurysms. Three of four patients developed symptomatic vasospasm, and two required balloon angioplasty. Three patients achieved good outcomes. The eldest died from severe vasospasm that was unresponsive to angioplasty. Reversible cardiac failure associated with subarachnoid hemorrhage may be due the neurogenic stunned myocardium. Frequent symptomatic vasospasm occurs, possibly related to poor cardiac output and the inability to optimize hyperdynamic hypervolemic therapy, particularly with compromised volume status. These patients can be treated with endovascular therapy of the aneurysms and balloon angioplasty as needed. With aggressive management, patients can recover from these reversible cardiac complications.

Adult↗

Endovascular management of poor-grade aneurysmal subarachnoid hemorrhage in the geriatric population.

BACKGROUND AND PURPOSE: The incidence of poor-grade (Hunt and Hess grade IV and V) subarachnoid hemorrhage (SAH) is higher in elderly patients (>70 years) than in younger groups. The aim of this retrospective study was to analyze the outcome of these poor grade elderly patients after endovascular treatment. METHODS: We retrospectively reviewed the clinical records of 27 patients older than 70 years who underwent endovascular treatment for aneurysmal SAH between January 1996 and July 2002. Thirteen patients with SAH and a poor Hunt and Hess grade at initial presentation had been treated by endovascular means. Their outcomes were assessed by the using the Glasgow Outcome Scale (GOS). RESULTS: Two patients (15%) had a good outcome according to the GOS. Three patients (23%) were moderately disabled, two (15%) were severely disabled at the time of discharge from the hospital, and six (47%) died. Five patients (38%) developed clinical vasospasm and underwent balloon angioplasty. Three procedure-related deaths occurred (23%). CONCLUSION: Endovascular treatment has modified the management of poor-grade SAH in elderly patients, most of whom are high-risk surgical candidates. Endovascular treatment can be administered early after the initial ictus, reducing the risk of rebleeding and providing an option to pursue aggressive triple-H therapy. Symptomatic vasospasm can also be treated by endovascular means in the initial setting.

Aged↗

Bromodomains mediate an acetyl-histone encoded antisilencing function at heterochromatin boundaries.

Bromodomains bind acetylated histone H4 peptides in vitro. Since many chromatin remodeling complexes and the general transcription factor TFIID contain bromodomains, they may link histone acetylation to increased transcription. Here we show that yeast Bdf1 bromodomains recognize endogenous acetyl-histone H3/H4 as a mechanism for chromatin association in vivo. Surprisingly, deletion of BDF1 or a Bdf1 mutation that abolishes histone binding leads to transcriptional downregulation of genes located at heterochromatin-euchromatin boundaries. Wild-type Bdf1 protein imposes a physical barrier to the spreading of telomere- and mating-locus-proximal SIR proteins. Biochemical experiments indicate that Bdf1 competes with the Sir2 deacetylase for binding to acetylated histone H4. These data suggest an active role for Bdf1 in euchromatin maintenance and antisilencing through a histone tail-encoded boundary function.

Acetylation↗

Varicella-zoster vasculitis presenting with intracranial hemorrhage.

Cerebral vasculitis presenting with intracranial hemorrhage is a rare but known entity. We discuss here the case of a 61-year-old woman presenting with subarachnoid hemorrhage. Cerebral angiography showed vasculitic changes involving the small and medium-sized vessels. She also had a concomitant herpes zoster rash on her back. A 3-month follow-up angiogram revealed partial resolution of the vasculitic changes.

Brain↗