Chlorotyrosine protein adducts are reliable biomarkers of neutrophil-induced cytotoxicity in vivo

INTRODUCTION:A limitation for investigating the pathophysiological role of neutrophils in vivo is the lack of a reliable biomarker for neutrophil cytotoxicity in the liver. Therefore, we investigated if immunohistochemical detection of chlorotyrosine protein adducts can be used as a specific footprint for generation of neutrophil-derived hypochlorous acid in vivo.METHODS:C3Heb/FeJ mice were treated with 100 micrograms/kg endotoxin (ET) alone or in combination with 700 mg/kg galactosamine (Gal/ET). Some animals received additionally two doses of 10 mg/kg of the pancaspase inhibitor Z-VAD-fmk. An antibody against chlorotyrosine was used for the immunohistochemical analysis.RESULTS:At 6 h after Gal/ET, hepatocellular apoptosis was evident without increase in plasma ALT activities. Neutrophils accumulated in sinusoids but there was no evidence for chlorotyrosine staining. At 7 h after Gal/ET, about 54% of the sequestered neutrophils had extravasated, there was extensive necrosis and increased plasma ALT activities. Extensive immunostaining for chlorotyrosine, mainly colocalized with neutrophils, could be observed. Treatment with Z-VAD-fmk eliminated apoptosis, necrosis and the increase in plasma ALT values. Neutrophil extravasation was prevented but the overall number of neutrophils in the liver was unchanged. Chlorotyrosine staining was absent in these samples. After ET alone (7 h), sinusoidal neutrophil accumulation was similar to Gal/ET treatment but there was no apoptosis, neutrophil extravasation, ALT release or chlorotyrosine staining.CONCLUSIONS:Chlorotyrosine staining in liver samples correlated well with evidence of neutrophil-induced liver injury in the endotoxemia model. These results indicate that assessment of chlorotyrosine protein adduct formation by immunohistochemistry could be a useful marker of neutrophil-induced liver cell injury in vivo.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Pulmonary mantle cell lymphoma: a rare manifestation of an uncommon condition

Herein we describe the case of a 64-year old man with a history of mantle cell lymphoma found to have evidence of pulmonary parenchymal involvement by recurrence of his lymphoma. While lung involvement is not necessarily uncommon with Non-Hodgkin's lymphomas as a group, it is very rare for mantle cell lymphoma to involve the lung parenchyma. In addition, the radiographic manifestation of his pulmonary lymphoma as a discrete FDG-avid ground-glass lesion on chest imaging was also distinctly uncommon for pulmonary lymphoma which classically appears in one of three patterns: scattered ill-defined nodules, a bronchovascular/lymphangitic process, or pneumonic/alveolar consolidation effectively indistinguishable from bacterial pneumonia. Due to significant underlying lung disease our patient was not a candidate for high-dose conditioning and autologous stem cell transplantation. He was ultimately treated with rituximab and cladribine therapy and had early signs of clinical response at last correspondence

Cutaneous Pyoderma Gangrenosum of the Hand.

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Percutaneous needle biopsy for indeterminate renal masses: a national survey of UK consultant urologists

<p>Abstract</p> <p>Background</p> <p>The use of percutaneous needle biopsy in the evaluation of indeterminate renal masses is controversial and its role in management remains largely unclear. We set to establish current practice on this issue in UK urology departments.</p> <p>Methods</p> <p>We conducted a national questionnaire survey of all consultant urologists in the UK, to establish current practice and attitudes towards percutaneous needle biopsy in the management of indeterminate renal masses.</p> <p>Results</p> <p>139 (43%) consultant urologists never use biopsy, whereas 111 (34%) always employ it for the diagnosis of indeterminate renal masses. 75 (23%) urologists use biopsy only for a selected patient group. Mass in a solitary kidney, bilateral renal masses and a past history of non-renal cancer were the main indications for use of percutaneous biopsy. The risk of false negative results and biopsy not changing the eventual management of their patients were the commonest reasons not to perform biopsy.</p> <p>Conclusion</p> <p>There is a wide and varied practice amongst UK Consultant Urologists in the use of percutaneous biopsy as part of the management of indeterminate renal masses. The majority of urologists believe biopsy confers no benefit. However there is a need to clarify this issue in the wake of recent published evidence as biopsy results may provide critical information for patients with renal masses in a significant majority. It not only differentiates benign from malignant tissue but can also help in deciding the management option for patients undergoing minimally invasive treatments.</p

MRI in Japanese encephalitis

We document the MRI features in seven patients with Japanese encephalitis. MRI was carried out on a 1.5 T system within 10-60 days of onset. In all the patients MRI revealed bilateral thalamic lesions, haemorrhagic in five. Signal changes were present in the cerebrum in four patients, the midbrain and cerebellum in three each, the pons in two and the basal ganglia in one. The lesions were haemorrhagic in three of the four patients with lesions in the cortex, two of the three with lesions in the midbrain and cerebellum, but the pontine lesions were haemorrhagic in both patients. Spinal cord involvement was seen in one of the three patients who underwent MRI. In two patients MRI was repeated 3 years after the onset, showing marked reduction in abnormal signal; and all the lesions gave low signal on both T1- and T2-weighted images. Bilateral thalamic involvement, especially haemorrhagic, may be considered characteristic of Japanese encephalitis, especially in endemic areas

Rapidly expanding thenar eminence ganglion: a case report

Introduction This study documents the first reported case of a rapidly growing (volar) thenar eminence ganglion arising form the first carpometacarpal joint, masquerading as a sarcoma. The discussion informs the hand surgeon on the evidence regarding the unusual presenting features. Case presentation An 85 year old left hand dominant female presented with a six week history of rapidly growing lump on the thenar eminence. Clinical examination revealed a non-tender large lobulated mobile swelling measuring 5 × 4 cm and involving the whole thenar eminence. Conclusion Ganglia may present from the thenar eminence and are a source of diagnostic confusion

Rapidly expanding thenar eminence ganglion: A case report

Introduction This study documents the first reported case of a rapidly growing (volar) thenar eminence ganglion arising form the first carpometacarpal joint, masquerading as a sarcoma. The discussion informs the hand surgeon on the evidence regarding the unusual presenting features. Case presentation An 85 year old left hand dominant female presented with a six week history of rapidly growing lump on the thenar eminence. Clinical examination revealed a non-tender large lobulated mobile swelling measuring 5 × 4 cm and involving the whole thenar eminence. Conclusion Ganglia may present from the thenar eminence and are a source of diagnostic confusion

A novel method for spectrophotometric determination of pregabalin in pure form and in capsules

<p>Abstract</p> <p>Background</p> <p>Pregabalin, a γ-amino-n-butyric acid derivative, is an antiepileptic drug not yet official in any pharmacopeia and development of analytical procedures for this drug in bulk/formulation forms is a necessity. We herein, report a new, simple, extraction free, cost effective, sensitive and reproducible spectrophotometric method for the determination of the pregabalin.</p> <p>Results</p> <p>Pregabalin, as a primary amine was reacted with ninhydrin in phosphate buffer pH 7.4 to form blue violet colored chromogen which could be measured spectrophotometrically at λ_max402.6 nm. The method was validated with respect to linearity, accuracy, precision and robustness. The method showed linearity in a wide concentration range of 50-1000 μg mL^-1with good correlation coefficient (0.992). The limits of assays detection was found to be 6.0 μg mL^-1and quantitation limit was 20.0 μg mL^-1. The suggested method was applied to the determination of the drug in capsules. No interference could be observed from the additives in the capsules. The percentage recovery was found to be 100.43 ± 1.24.</p> <p>Conclusion</p> <p>The developed method was successfully validated and applied to the determination of pregabalin in bulk and pharmaceutical formulations without any interference from common excipients. Hence, this method can be potentially useful for routine laboratory analysis of pregabalin.</p

Leiomyosarcoma of the maxilla as second malignancy in retinoblastoma

Patients with hereditary retinoblastoma are at increased risk of second primary tumor, the commonest tumor being osteosarcoma. Leiomyosarcoma developing as second primary neoplasm in retinoblastoma patients is unusual and most have occurred in the field of previous radiotherapy. Although with aggressive therapy better survival can be achieved, the overall prognosis of patients developing these second neoplasms is poor. In this report we present a case of leiomyosarcoma of the maxilla as a second neoplasm in a patient with bilateral retinoblastoma which has developed outside the radiation field