Challenging immunodominance of influenza-specific CD8+ T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.

Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8+ T cells to mount robust responses. We elucidate the HLA-A*68:01+CD8+ T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145+CD8+ T cell responses. Dissecting A68/NP145+CD8+ T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145+CD8+ memory T cells with clonally expanded TCRαßs, while low-responders display A68/NP145+CD8+ T cells with predominantly naïve phenotypes and non-expanded TCRαßs. Single-cell index sorting and TCRαß analyses link expansion of A68/NP145+CD8+ T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8+ T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8+ T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.

An efficient protocol for the production of triploid plants from endosperm callus of neem, Azadirachta indica A. Juss.

Triploid plants of neem were obtained by immature endosperm culture. Immature seeds, at the early dicotyledonous stage of embryo development, is the best explant to raise endosperm callus on MS + NAA (5 mumol/L) + BAP (2 mumol/L) + CH (500 mg L-1). Maximum shoot bud differentiation from the endosperm callus occurred on MS + 5 mumol/L BAP. Shoots were multiplied by forced axillary branching and rooted in vitro. The plants were established in soil. Over 66% of the plants were triploid with chromosome number 2n = 3x = 36. A characteristic feature of the shoots of endosperm origin is the presence of a large number of multi-cellular glands.

Pleuropulmonary abnormalities in patients with systemic lupus erythematosus: assessment with high resolution computed tomography, chest radiography and pulmonary function tests.

OBJECTIVE: To assess the nature of pleuropulmonary abnormalities, with particular reference to interstitial lung disease (ILD), in patients with systemic lupus erythematosus (SLE). METHODS: 29 patients were prospectively evaluated using high resolution computed tomography (HRCT), plain chest radiography (CXR) and pulmonary function tests (PFTs). Clinical assessments, drug therapy, disease activity, smoking status and serologic markers were also noted. RESULTS: The HRCT was abnormal in 72% (20/29) of patients, while 34% (10/29) had an abnormal CXR. The most frequently detected primary HRCT abnormality was suggestive of ILD and was noted in 11 patients (38%) In 9 of these, ILD was clinically unsuspected, including one patient who had an HRCT suggestive of active alveolitis. Pleuropericardial abnormalities were seen on HRCT in 5 patients (17%). Of 15 patients who were asymptomatic, and had a normal examination, normal CXR and normal PFTs, four (26%) had HRCT features of ILD. There was no correlation between the HRCT appearances and symptoms, disease duration, ds-DNA titres, smoking history or non-pulmonary involvement. Although no statistical significance was noted between abnormal pulmonary function tests and ILD on HRCT (0.10 < p < 0.20), a trend towards significance was noted between disease activity and ILD (0.05 < p < 0.01). CONCLUSION: HRCT is more sensitive than PFTs or CXR in the evaluation of pleuropulmonary disease in SLE. We report an unusually high prevalence of HRCT appearances suggestive of ILD in patients with SLE. Subclinical lung disease is common in patients with SLE.

High-resolution chest CT in systemic lupus erythematosus.

OBJECTIVE: The purpose of our study was to identify high-resolution CT (HRCT) findings in patients with systemic lupus erythematosus (SLE) and to determine their significance by correlation with clinical findings, plain chest radiography, and pulmonary function testing. SUBJECTS AND METHODS: Thirty-four patients with documented SLE were prospectively studied. All patients had plain chest radiography (posteroanterior and lateral) thoracic spiral CT, HRCT, and pulmonary function testing performed. RESULTS: HRCT abnormalities were identified in 24 patients (70%), pulmonary function abnormalities were present in only 14 patients (41%), and the plain chest radiograph was abnormal in only 8 patients (24%). The most common CT findings were: interstitial lung disease (n = 11), bronchiectasis (n = 7), mediastinal or axillary lymphadenopathy (n =6), and pleuropericardial abnormalities (n =5). No correlation was found between disease activity, duration of disease, chest symptoms, drug therapy, smoking history, and the presence of abnormal HRCT findings. More importantly, no correlation was found between pulmonary function abnormalities and the presence or grade of interstitial lung disease or bronchiectasis as determined by HRCT. CONCLUSION: The results of this study, the first to describe the HRCT findings in SLE, suggest that airways disease, lymphadenopathy, and interstitial lung disease are common thoracic manifestations of SLE, whereas pleural abnormalities are less common than previously suggested. HRCT evidence of airways disease and interstitial lung disease was frequently present despite an absence of symptoms, a normal chest radiograph, and normal pulmonary function testing. HRCT provides a sensitive and noninvasive technique for detecting pulmonary involvement in SLE, with the added advantage that it can be performed in all patients, including those too compromised to undergo a surgical procedure. In patients with advanced disease, HRCT permits procedures such as bronchoalveolar lavage and lung biopsy to be directed toward areas of particular interest.

Do non-steroidal anti-inflammatory drugs have an effect on gastric cell turnover?

AIM: To study the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on gastric cell turnover using an in vitro immunohistochemical method of bromodeoxyuridine (BrDU) uptake. METHODS: Thirty patients undergoing routine upper gastrointestinal endoscopy were studied. Sixteen had taken NSAIDs daily for more than 3 months and there were 14 age-matched controls. Endoscopic gastric antral biopsies were obtained and stained immediately using the BrDU technique. Cell proliferation was expressed as a labelling index percentage (LI%) defined as the number of BrDU-labelled nuclei in 10 gastric glands, expressed as a percentage of the total cells in the gastric gland. RESULTS: Gastric infection with Helicobacter pylori was excluded in all patients. Of the 16 patients on NSAIDs, four had gastritis, four had erosions or ulceration and eight had a normal examination. Endoscopy was normal in all patients in the control group. The LI% (mean +/- S.E.M.) in the entire NSAID group was 4.09 +/- 0.29 and in the control group 3.57 +/- 0.29. No significant difference was observed. In the NSAID patients with gastritis and erosions or ulceration, the LI% was 4.99 +/- 0.61 and 3.07 +/- 0.32, respectively. There was no significant difference in LI% between the endoscopic subgroups of patients on NSAIDs or between patients on NSAIDs who had normal endoscopy and the control patients. CONCLUSION: These results provide evidence that refutes the hypothesis that the prevalence of NSAID gastropathy is due to an effect on gastric cell turnover.

Lymphatic obstruction in rheumatoid arthritis.

We describe four patients with rheumatoid arthritis and unilateral upper limb oedema. In all cases, qualitative lymphoscintigraphy showed lymphatic obstruction in the affected limb.

Symptomatic enlarged iliopsoas bursae in the presence of a normal plain hip radiograph.

The clinical and radiological features of seven cases of enlarged iliopsoas bursae are presented, all of which had normal plain hip radiographs. Two cases had rheumatoid arthritis, one had septic arthritis diagnosed by synovial biopsy and the remaining four cases occurred as isolated findings, in the absence of any recognized hip pathology. A communication with the hip joint was demonstrated in one case associated with septic arthritis. All patients presented with symptoms of hip pain and limitation of movement. Two patients had a groin mass, one of which produced localized pressure symptoms and retroperitoneal extension. All patients had an arthrogram or bursogram performed. In the two cases where a mass was palpable, ultrasound and computed tomography were performed. We conclude that, in the presence of persistent hip pain or reduced range of movement, an enlarged iliopsoas bursa should be considered as a potential diagnosis, even in cases where the plain hip radiograph is normal.

Percutaneous endoscopic gastrostomy--its application in patients with neurological disease.

We performed percutaneous endoscopic gastrostomy (PEG) in 30 patients with prolonged swallowing difficulty (> 4 weeks duration). The average procedure time was 25 minutes. PEG insertion was done on an outpatient basis in four patients. The complication rate was 10% and included failed insertion, peristomal infection and herniation of the gastric mucosa at the gastrostomy exist site. At follow-up, the PEG tube continued to function in 18/22 of the surviving patients with a median in-use time of 85 days. Seven patients died from their original disease. Over a 28-day period, the weight gain among the patients ranged from 3kg to 7kg (mean 4.5kg) and average serum albumin increased from 29g/dl to 35g/dl. This confirms that PEG is a safe, easy and effective method of long-term enteral feeding in patients with neurological disease.