A murine cytomegalovirus-neutralizing monoclonal antibody exhibits autoreactivity and induces tissue damage in vivo.

The autoreactivity of murine cytomegalovirus (MCMV)-neutralizing monoclonal antibody (mAb) AC1 was examined in vitro and in vivo. Both mAb AC1 and a human antiserum reactive with U1-small nuclear ribonucleoprotein (U1-snRNP) stained uninfected mouse embryo fibroblasts (MEF) in a speckled nuclear pattern and reacted with 70,000 molecular weight (MW) MEF nuclear antigens by immunoblotting, suggesting that mAb AC1 cross-reacted with the 70,000 MW component of U1-snRNP. However, only mAb AC1 cross-reacted with an additional epithelial cytoplasmic autoantigen present in cultured HEp2 cells. On tissue sections from uninfected mice, mAb AC1 predominantly reacted with a component of central and peripheral nervous systems, although cross-reactivity with the stratum spinosum of the skin and the outer sheath of hair follicles was also observed. Immunoblotting revealed that mAb AC1 reacted with phosphorylated epitopes present on a 98,000 MW MCMV structural protein and the 200,000 MW mouse neurofilament protein (NFP). Treatment of uninfected mice with mAb AC1 resulted in a severe interstitial pneumonia with greatly thickened and congested alveolar septa. Severe oedema of the hypodermis and a mild mesangial proliferative glomerulonephritis were also observed. These results demonstrate that a mAb reacting with a MCMV structural phosphoprotein which can protect mice against the dissemination of MCMV, can also promote the development of autoimmune disease. Therefore, the production of such cross-reactive antibodies may be an important mechanism in the development of autoimmunity following viral infection.     

Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity. METHODS: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.     

adaptive fourier threshold filtering: A method to reduce noise and incoherent artifacts in high resolution cardiac images

We introduce an image processing method which reduces white noise and random artifacts in sets of high resolution, time resolved images. At each pixel, the processing consists of: (1) the isolation of a time intensity curve (TIC), (2) Fourier transformation of each TIC, (3) application of a threshold to remove low intensity coefficients, (4) inverse transformation to generate noise reduced TICS which are recombined to form images with improved signal-to-noise ratio (SNR). Noise filtering by Fourier thresholding is demonstrated on a set of cardiac images, resulting in a reduction of the noise energy by approximately 90%.     

Investigation of focal hepatic lesions: Is tomographic red blood cell imaging useful?

Noninvasive diagnosis of cavernous hemangioma of the liver is an important step in the investigation of patients with focal hepatic lesions since biopsy may result in life-threatening hemorrhage. To determine the diagnostic accuracy of 99m-technetium red blood cell (^99mTc-RBC) imaging with tomography, 50 patients with various types of focal liver lesions were studied. Thirty-two patients had 45 hemangiomas and 7 other benign lesions while 18 patients had either primary (n=8) or secondary (n=10) hepatic malignancies. Tomographic imaging identified 12 more hemangiomas than planar imaging, improving sensitivity from 53% to 80%, and was found most useful for detection of smaller lesions (mean size, 2.1 cm). Specificity for hemangiomas was 100% with all lesions greater than 1.9 cm showing the characteristic scintigraphic pattern of blood-pooling on delayed images. There was excellent agreement between 2 independent observers concerning interpretation of tomographic images (89% for the hemangioma group and 100% for other patients). Therefore^99mTc-RBC scintigraphy with tomography is an accurate diagnostic technique in the investigation of cavernous hemangiomas. Its major value resides in its ability to distinguish hemangiomas from other types of hepatic pathology.

---

Resumen El diagnóstico no invasivo del hemangioma cavernoso del hígado es un paso de importancia en el proceso de investigación de pacientes con lesiones hepáticas focales, puesto que la biopsia puede resultar en hemorragia de consecuencias potencialmente fatales. Con el objeto de determinar la certeza diagnóstica de la tomografía con glóbulos rojos marcados con tecnecio 99m, se estudiaron 50 pacientes con varios tipos de lesiones hepáticas focales. Treinta y dos pacientes presentaron 45 hemangiomas y 7 lesiones benignas, en tanto que 18 pacientes presentaron neoplasias malignas primarias (n=8) o secundarias (n=10). Las imágenes tomográficas obtenidas por este método lograron identificar 12 hemangiomas más, en comparación con imágenes convencionales, aumentando la sensibilidad de 53% a 80%, y demostró ser de máxima utilidad para la detección de las lesiones más peque¯nas (tamaño promedio, 2.1 cm). La especificidad para los hemangiomas fue 100%, con todas las lesiones mayores de 1.9 cm exhibiendo el patrón centelleográfico característico de estancamiento sanguíneo en las imágenes tardías. Se encontró excelente correlación entre 2 observadores independientes en la interpretación de las imágenes tomográficas (89% para el grupo de pacientes con hemangiomas y 100% para el resto de los pacientes). En consecuencia, la escintigrafía con glóbulos rojos marcados con^99mTc aparece como una técnica certera en el diagnóstico de los hemangiomas cavernosos. Su mayor valor reside en su habilidad para diferenciar los hemangiomas de otra clase de patología.

---

Résumé Le diagnostic non invasif d'hémangiome caverneux du foie est une étape importante dans l'investigation des patients ayant des lésions hépatiques focales, puisque la biopsie risque de se résoudre par une hémorrhagie menaçant le pronostic vital. Pour définir la précision diagnostique de la tomoscintigraphie après marquage des hématies au technetium 99m (^99mTc), on a étudié 50 patients ayant des types différents de lésions focales du foie. Trente-deux patients avaient 45 hémangiomes et 7 lésions bénignes tandis que 18 patients avaient des tumeurs hépatiques malignes soit primaires (n=8) soit secondaires (n=10). L'imagerie tomographique a identifié 12 hémangiomes de plus que l'imagerie planaire, améliorant la sensibilité de 53% à 80% et s'est avérée très utile pour détecter les lésions plus petites (taille moyenne, 2.1 cm). La spécificité pour les hémangiomes était de 100% pour toutes les lésions dépassant 1.9 cm montrant les caractères scintigraphiques typiques d'accumulation de sang sur les images retardées. Il y a eu concordance totale entre 2 observateurs indépendents sur l'interprétation des images tomographiques (89% pour le groupe des hémangiomes et 100% pour les autres patients). Voilà pourquoi la scintigraphie^99mTc avec tomographie est une technique de diagnostic précis dans l'investigation des hémangiomes caverneux. Sa valeur essentielle est sa capacité de distinguer les hémangiomes des autres types de pathologie hépatique.

     

Identifying High Risk Groups and Quantifying Absolute Risk of Cancer After Kidney Transplantation: A Cohort Study of 15 183 Recipients

Transplant recipients have increased cancer risk, but data on risk variation across different patient groups are sparse. Rates and standardized rate ratios (SRR) of cancer (all sites, excluding nonmelanocytic skin and lip cancer) compared to the general population were calculated, using Australia and New Zealand Dialysis and Transplant Registry data. Within the transplant population, risk factors were identified (hazard ratios: HR; 95% CI) and absolute risk estimated for recipient groups. A total of 1642 (10.8%) of 15 183 recipients developed cancer. Risk was inversely related to age (SRR 15-30 children, 2 if >65 years). Females aged 25-29 had rates equivalent to women aged 55-59 from the general population. Age trend for lymphoma, colorectal and breast risk was similar; melanoma showed less variability across ages, prostate showed no risk increase. Within the transplanted population, risk was affected by age differently for each sex (p = 0.007), elevated by prior malignancy (HR 1.40; 1.03-1.89), white race (HR 1.36; 1.12-1.89), but reduced by diabetic end-stage kidney disease (ESKD) (HR 0.67; 0.50-0.89). Cancer rates in kidney recipients are similar to nontransplanted people 20-30 years older, but absolute risk differs across patient groups. Men aged 45-54 surviving 10 years have cancer risks varying from 1 in 13 (non-white, no prior cancer, diabetic ESKD) to 1 in 5 (white, prior cancer, other ESKD).