Two flares of Still’s disease after two doses of the ChAdOx1 vaccine

Clinical Rheumatology - We report the case of an 18-year-old male with Still’s disease for the last 3 years, in remission, who developed two flares of his disease after receiving two...     

Evaluation of (111)In-labeled macrocyclic chelator-amino acid derivatives for cancer imaging

PurposeWe evaluated new ¹¹¹In-labeled amino acid derivatives, in which the amino acids are conjugated with1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) or 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A).MethodsDOTA-aminoalanine (DOTA-A), DOTA-aminohomoalanine (DOTA-H), DOTA-lysine (DOTA-L), DO2A-alanine (DO2A-A), DO3A-alanine (DO3A-A) and DO3A-homoalanine (DO3A-H) were labeled with ¹¹¹In. In vitro cell uptake assays were performed usingHep3B (a human hepatoma cell line), CT26 (a mouse colon cancer cell line) and U87MG (a human glioma cell line). In vitro cell uptake inhibition assays were performed using U87MG and ¹¹¹In-DO3A-H. U87MG bearing xenografted mice were subject to biodistribution, SPECT imaging, autoradiography, and immunohistochemistry studies.ResultsOf the amino acid derivatives and cell lines examined, U87MG and ¹¹¹In-DO3A-H showed highest uptake in vitro. This uptake was blocked by 2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid (BCH) and by tryptophan. ¹¹¹In-DO3A-HSPECT imaging of U87MG bearing xenografted mice visualized tumors (mean tumor-to-muscle ratio 3.16±0.74). Autoradiography and immunohistochemistry revealed that ¹¹¹In-DO3A-H uptake matched L-type amino acid transporter 1 expression.ConclusionTumor uptake was successfully imaged using ¹¹¹In-DO3A-H in U87MG bearing xenografted mice. ¹¹¹In-DO3A-H appears to be useful for imaging tumors expressing L-type amino acid transporter.     

Peritoneal Tuberculosis: Laparoscopic Patterns and Its Diagnostic Accuracy

We report laparoscopic findings in 38 proven cases of peritoneal tuberculosis. The laparoscopic appearances can be classified into three types: thickened peritoneum with miliary yellowish white tubercles with or without adhesions (n = 25), only thickened peritoneum with or without adhesions (n = 8), and fibroadhesive pattern (n = 5). Biopsies were avoided from fibroadhesive lesions due to risk of complications. Visual diagnosis was accurate in 95% of patients. In comparison, in 27 (82%) of 33 patients, the examination enabled a histologic diagnosis to he made on the basis of typical granulomas. The combined use of guinea pig inoculation and culture isolated Mycobacterium tuberculosis in six (37.5%) of 16 patients. Mycobacteria were scarcely (3%) seen on histological sections. We conclude that, although target biopsy is an effective method of obtaining an early diagnosis of peritoneal tuberculosis, chemotherapy may be started on the basis of visual laparoscopic appearances alone.     

Association between TNF-�� and Entamoeba histolytica Diarrhea

An association between tumor necrosis factor α (TNF-α) and Entamoeba histolytica diarrhea was assessed in a cohort of 138 non-related Bangladeshi children who have been prospectively followed since 2001. Peripheral blood mononuclear cells (PBMCs) obtained at study entry were purified, cultured, and stimulated with soluble amebic antigen before cytokine measurement from supernatant. Higher levels of TNF-α were associated with increased risk of first (P = 0.01) and recurrent E. histolytica-related diarrheal episodes (P = 0.005). Children who developed E. histolytica diarrhea had significantly higher TNF-α protein levels than those who experienced asymptomatic E. histolytica infection (P value = 0.027) or no infection (P value = 0.017). Microarray studies performed using RNA isolated from acute and convalescent whole blood and colon biopsy samples revealed higher but non-significant TNF-α messenger RNA (mRNA) levels in subjects with acute E. histolytica diarrhea compared with convalescence. We conclude that there is an association between higher TNF-α production and E. histolytica diarrhea.     

Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192

OBJECTIVE: To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFbeta1 and TGFbeta2. RESULTS: Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). CONCLUSION: We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.     

Segment-2 sequence analysis and cross-neutralization studies on some Indian bluetongue viruses suggest isolates are VP2-variants of serotype 23

Sequence analysis of segment 2 (seg-2) of three Indian bluetongue virus (BTV) isolates, Dehradun, Rahuri and Bangalore revealed 99% nucleotide identity amongst them and 96% with the reference BTV 23. Phylogenetic analysis grouped the isolates in ‘nucleotype D’. The deduced amino acid (aa) sequence of the Bangalore isolate showed a high variability in a few places compared to other isolates. B-cell epitope analyses predicted an epitope that is present exclusively in the Bangalore isolate. Two-way cross serum neutralization confirmed that Bangalore isolate is antigenically different from the other two isolates. The results of this study suggest that these three isolates are VP2 variants of BTV 23. This signifies that non-cross-neutralizing variants of the same BTV serotype should be included in vaccine preparation.     

Development and validation of a simple sensitive enzyme immunoassay (EIA) for GH determination in buffalo plasma

A simple and highly sensitive enzymeimmunoassay (EIA) for GH determination in buffalo plasma on microtitreplates using biotin-streptavidin amplification system and the second antibody coating was developed. Biotin was coupled to GH and used to bridge between streptavidin-peroxidase and immobilized antiserum in competitive assay. The EIA was carried out directly in 100 microL buffalo plasma. The GH standards ranging from 0.05 ng/well/100 microL to 12.8 ng/well/100 microL were prepared in hormone free plasma collected from an aged (> 15 years) senile buffalo. The sensitivity of the EIA procedure was 50 pg/well GH. which corresponded to 0.50 ng/mL plasma; the 50% relative binding sensitivity was seen at 800 pg/well/100 microL. Plasma volumes for the EIA, viz., 25, 50, and 100 microL did not influence the shape of standard curve, even though a slight drop in the OD450 was seen with higher plasma volumes. For the biological validation of the assay, 12 Murrah buffalo calves were used. Six of these were administered synthetic bovine growth hormone-releasing factor (10 microg/100 kg body weight, i.v., and the remaining six animals were administered sterile normal saline and kept as controls. Jugular blood samples were collected at -60, -45, -30, -15, -10, -5, 5, 10, 15, and 30 min and, thereafter, at an interval of 15 min using an indwelling jugular catheter, beginning 1 h prior to GRF injection up to 8 h post treatment. In all animals, a peak of GH was recorded within 5 to 20 min of GRF administration, which confirms the biological validation of the EIA. To confirm homogeneity of buffalo GH with bovine GH, a parallelism test was conducted between the buffer standard curve of bovine GH and GH measured from serial dilution of buffalo plasma containing a high level of endogenous growth hormone.