Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians

Background

The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.

Methods

Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.

Objectives

To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.

Results

Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.

Conclusion

Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Desensitization of endothelial P2Y1 receptors by PKC-dependent mechanisms in pressurized rat small mesenteric arteries

Background and purpose:

Extracellular nucleotides play a crucial role in the regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1 receptors evokes concentration-dependent full dilatation of resistance arteries. However, this GPCR can desensitize upon prolonged exposure to the agonist. Our aim was to determine the extent and nature of P2Y1 desensitization in isolated and pressurized rat small mesenteric arteries.

Experimental approach:

The non-hydrolyzable selective P2Y1 agonist ADPβS (3 µM) was perfused through the lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and endothelial cell [Ca²⁺]_i were obtained in the presence and absence of inhibitors of protein kinase C (PKC).

Key results:

ADPβS evoked rapid dilatation to the maximum arterial diameter but faded over time to a much-reduced plateau closer to 35% dilatation. This appeared to be due to desensitization of the P2Y1 receptor, as subsequent endothelium-dependent dilatation to acetylcholine (1 µM) remained unaffected. Luminal treatment with the PKC inhibitors BIS-I (1 µM) or BIS-VIII (1 µM) tended to augment concentration-dependent dilatation to ADPβS (0.1–3 µM) and prevented desensitization. Another PKC inhibitor, Gö 6976 (1 µM), was less effective in preventing desensitization. Measurements of endothelial cell [Ca²⁺]_i in pressurized arteries confirmed the P2Y1 receptor but not M₃ muscarinic receptor desensitization.

Conclusions and implications:

These data demonstrate for the first time the involvement of PKC in the desensitization of endothelial P2Y1 receptors in pressurized rat mesenteric arteries, which may have important implications in the control of blood flow by circulating nucleotides.     

Minimally invasive anterolateral approach to the hip: risk to the superior gluteal nerve

BACKGROUND: Minimally invasive approaches to the hip show promise of less muscle trauma compared to conventional approaches. What is the risk of damage to the superior gluteal nerve? We studied the course of the superior gluteal nerve. METHOD: 20 legs of 11 formalin-fixed Caucasian cadavers were dissected and the course and the distances of the superior gluteal nerve branches from the tip of the greater trochanter were documented. RESULTS: The branch of the gluteal superior nerve leading to the gluteal minimus muscle was 33 (20-50) mm from the tip of the greater trochanter, within a deeper layer. The nearest point of the superior gluteal nerve branches from the tip of the greater trochanter in the posterior region was 19 (10-30) mm, in the middle region 20 (20-30) mm and in the anterior region 20 (10-35) mm. In half of the cases, a distal intermuscular branch between gluteal medius and tensor fasciae latae muscle could be found, mean 27 (10-40) mm caudal and 38 (25-60) mm ventral to the tip of the greater trochanter. This distal branch is considered to create a loop with upper branches of the superior gluteal nerve within the tensor fasciae muscle. INTERPRETATION: The safe zone for the superior gluteal nerve was smaller than previously reported. Use of a minimal direct lateral approach puts the inferior branches within the gluteal medius at risk; however, a minimal anterolateral approach to the hip may compromise branches of the superior gluteal nerve to the tensor fasciae latae muscle.