Detection of adenovirus hepatitis and acute liver failure in allogeneic hematopoietic stem cell transplant patients.

Human adenovirus (HAdV) is an important cause of the common cold and epidemic keratoconjunctivitis in immunocompetent individuals. In immunocompromised patients, HAdV can sometimes cause severe infection such as cystitis, gastroenteritis, pneumonia, encephalitis, hepatitis, or disseminated disease, resulting in significant morbidity and also mortality. In particular, severe cases have been reported in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Indeed HAdV has been recognized as a pathogen that requires careful monitoring in allo-HSCT patients. While HAdV hepatitis leading to severe acute liver failure is rare, such liver failure progresses rapidly and is often fatal. Unfortunately, HAdV hepatitis has few characteristic symptoms and physical findings, which makes it difficult to promptly confirm and start treatment. We report here four cases of HAdV hepatitis after allo-HSCT and their autopsy findings.

Retinal vascular features associated with risk of branch retinal vein occlusion.

PURPOSE/AIM: To identify retinal vascular features that precede the development of branch retinal vein occlusion (BRVO) by comparing case eyes and fellow eyes. MATERIALS AND METHODS: We identified 25 persons who attended an annual health screening program at Osaka Health Science Center, Osaka, Japan, and then developed BRVO in one eye between 1995 and 2009. We retrospectively reviewed retinal images of these subjects taken 1-5 years prior to the development of BRVO and compared the prevalence of retinal vascular features between case eyes and contralateral fellow eyes. Potential local retinal vascular features considered were (1) severe arterio-venous (AV) nicking, (2) a smaller angle at the crossing of the arteriole and venule, (3) double crossing, (4) crossing near venular bifurcation and (5) isolated retinopathy. The central retinal artery equivalent (CRAE), vein equivalent (CRVE) and AV ratio (CRAE divided by CRVE) were quantitatively estimated using a standardized imaging software (University of Wisconsin). RESULTS: Compared to the fellow eye, severe AV nicking (39.1% versus 2.6%, <0.001), isolated retinopathy (47.8% versus 7.69%, p < 0.001) and a smaller angle at the crossing site (82.6% versus 46.2%, p = 0.005) were more prevalent in eyes with BRVO compared with fellow eyes. Case eyes had a significantly smaller AV ratio at 1-5 years prior to the development of BRVO compared with fellow eyes (0.68 versus 0.73, p = 0.03). CONCLUSIONS: In addition to severe AV nicking, a well-known sign linked to BRVO, this study identified two new potential retinal vascular features--isolated retinopathy and a smaller angle at the crossing site--associated with BRVO development. We also found that a discrepancy in the AV ratio between eyes (i.e. a smaller AV ratio than the fellow eye) can be a quantitative indicator of a higher BRVO risk. These findings warrant further validation in longitudinal studies.

Mantle cell lymphoma manifesting neurological symptoms similar to those of hypertrophic cranial pachymeningitis.

The patient was a 58-year-old man, who presented with headache and myodesopsia. He demonstrated papilledema and hemorrhage in the fundus of the left eye and MRI findings showed localized hypertrophic dura mater. He was diagnosed as having hypertrophic cranial pachymeningitis and treated with antibiotics and prednisolone. However, the patient complained of persistent headache. Therefore, CT scans of the chest and abdomen were obtained. These images demonstrated superficial and intraabdominal lymphadenopathy and a histological diagnosis of mantle cell lymphoma was made on biopsy of an inguinal mass. Specimen obtained at craniotomy also showed the same lymphoma cells diffusely infiltrating the dura mater. Complete remission of the lymphoma including disappearance of hypertrophic dura mater was obtained after 4 courses of rituximab plus hyper-CVAD alternating with high-dose methotrexate and cytarabine, and the neurological manifestation improved thereafter. Subsequently, he underwent autologous peripheral blood stem cell transplantation. Hypertrophic pachymeningitis is a chronic progressive inflammatory disorder with hypertrophic dura mater of brain and spinal cord, caused by diverse illnesses. Mantle cell lymphoma infiltrating the dura mater is extremely rare, and has not been reported previously. In some cases of hematological malignancy with hypertrophic pachymeningitis, dural biopsy is required to differentiate the etiology.

The CD70-CD27 interaction during the stimulation with dendritic cells promotes naive CD4(+) T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans.

CD70 expressed on dendritic cells (DCs) has been shown to play a critical role in inducing effective CD8(+) T cell responses and a T(h)1 response in mice. However, it has not been extensively examined whether human primary DCs express CD70 and whether the CD70-CD27 interaction promotes naive CD4(+) T cells to acquire the ability to produce effector cytokines during the DC-T cell interaction in humans. Here, we show that human myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells stimulated with CD40 ligand together with pro-inflammatory cytokines or Toll-like receptor ligands express CD70. Thymic stromal lymphopoietin plus prostaglandin E(2) also induced CD70 on mDCs. Naive CD4(+) T cells stimulated with DCs but not with anti-CD3/CD28 microbeads expressed CD70. Stimulation with CD70 together with anti-CD3/CD28 microbeads imparted the ability to produce T(h)1 (IFN-gamma), T(h)2 (IL-4, IL-5, IL-13) cytokines, IL-2 and tumor necrosis factor-alpha to naive CD4(+) T cells. The production of IFN-gamma was associated with the induction of T-bet. Naive CD4(+) T cells stimulated with mDCs acquired an enhanced ability to produce a broad array of immunostimulatory cytokines in a CD70-dependent manner. These data suggest that human CD70 expressed on mDCs and activated T cells transmits a 'basal level' signal, rather than a 'polarizing' signal, to naive CD4(+) T cells, in that CD70 promotes the development of CD4(+) T cells that produce a variety of effector cytokines including both T(h)1 and T(h)2 types, thus contributing to the enhancement of a broad spectrum of immune responses.