Clinical significance of simultaneous measurement of reticulated platelets and large platelets in idiopathic thrombocytopenic purpura

Frequencies of reticulated platelets (RP) and large platelets (LP) among circulating platelets can now be simultaneously determined using the R-3000 automated reticulocyte counter (Sysmex, Kobe, Japan) equipped with special software. We measured frequencies of RP and LP in patients with idiopathic thrombocytopenic purpura (ITP. acute type n = 5; chronic type n = 39), and healthy normal controls (n = 20). In ITP patients, the platelet-associated IgG (PAIgG) level was also determined. Both RP and LP were significantly higher in chronic ITP patients than those in normal volunteers, and interestingly, the LP in acute ITP was significantly lower than that in chronic ITP although there was no significant difference in RP between acute and chronic ITP. Furthermore, we analyzed the changes in both RP and LP during the clinical course of ITP to monitor the therapeutic effect in 2 patients. An elevation of RP with a steep slope prior to a decrease in the platelet count level was observed. The RP significantly correlated with the PAIgG level. Simultaneous measurement of RP and LP may be helpful for the diagnosis of chronic ITP, for the differentiation of acute from chronic type and for the control of the efficacy of management in ITP, since RP seems to reflect the disease activity of ITP.     

Left coronary artery occlusion caused by a large thrombus on the left coronary cusp in a patient with a continuous-flow ventricular assist device

Despite continual improvements in ventricular assist device (VAD) therapy, various clinical issues are emerging. Importantly, various types of thromboembolic complications have been reported to date. Recently, we encountered a rare continuous-flow VAD-related thromboembolic event that resulted in acute myocardial infarction. A 26-year-old female who just underwent HeartMate II^® VAD implantation suddenly developed widespread anterolateral myocardial infarction on postoperative day 16. Echocardiography and aortography revealed a large thrombus on the left coronary cusp of the aortic valve that almost completely occluded the left coronary ostium. After VAD implantation, her aortic valve did not open, even at relatively low pump speeds; this was thought to be one of the causes for thrombus formation. Continuous suction of blood from the left ventricle and non-pulsatile flow into the ascending aorta resulted in a continuously closed aortic valve and stagnation of blood in the coronary cusp. Furthermore, both small body size (body surface area <1.3 m²) and postoperative right ventricular failure may have exacerbated blood stagnation and thrombus formation in this patient. We should have adjusted the anticoagulation and antiplatelet therapy protocols based on the patient’s condition. She underwent off-pump coronary artery bypass surgery and remained in clinically stable condition afterwards.     

The Potential of the Tumor Microenvironment to Influence Apo2L/TRAIL Induced Apoptosis

Apo2L/TRAIL ligation of specific cell surface receptors (DR4 and DR5) induces apoptosis of many malignant cells with little effect on normal cells. This anti-tumor capability has been demonstrated using cell lines of many tumor types, both in vitro and in vivo when the cells are grown as xenografts. We have extended these studies to investigate the efficacy of Apo2L/TRAIL against patient tumor xenografts in SCID mice and found that the growth of many tumors, both of primary and metastatic origin, can be inhibited by Apo2L/TRAIL. The basis of resistance to Apo2L/TRAIL induced apoptosis in malignant cells and normal cells is not completely understood, but it is known that a variety of factors including hypoxia, MMPs and cytokines present in the tumor microenvironment can influence the response of malignant cells to Apo2L/TRAIL. Currently, the clinical potential of several molecules targeting the Apo2L/TRAIL receptors DR4 and DR5 is being investigated. Our goal in this review is to provide a brief overview of a number of factors that have potential to influence the response of patient tumors to Apo2L/TRAIL.     

Granulocytic sarcoma presenting with lymph node infarction at disease onset

A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction.     

Riedel's thyroiditis containing cytologically atypically appearing B-cells: a case report

We report on a case of Riedel's thyroiditis containing cytologically atypically appearing B-cells. The patient was a 60-year-old Japanese female, who had a well-demarcated tumor that showed extensive growth from the right thyroid lobe into perithyroidal soft tissues. Histologically, the lesion consisted of two components. The central tumor-like portion of the mass showed spindle cells intermixed with abundant collagen fibers. In addition, scattered B-cells with large nuclei and multiple small, but conspicuous nucleoli were also present. At the periphery of the nodule, numerous plasma cells and small lymphocytes, as well as occasional B-immunoblasts and plasmablasts were growing between non-neoplastic thyroid follicles. An infiltration of thyroid follicles by B-cells also resulted in lymphoepithelial-like lesions. The specimen obtained from an enlarged cervical lymph node occurring 14 months later contained numerous mature plasma cells showing a sheet-like arrangement with occasional immature plasma cells and immunoblasts in the interfollicular area and medullary cords. The polyclonal nature of B-cells was demonstrated immunohistochemically and by polymerase chain reaction in both the thyroid gland and the lymph node lesion.     

Chronically increased transforming growth factor-beta1 strongly inhibits hippocampal neurogenesis in aged mice

There is increasing evidence that hippocampal learning correlates strongly with neurogenesis in the adult brain. Increases in neurogenesis after brain injury also correlate with improved outcomes. With aging the capacity to generate new neurons decreases dramatically, both under normal conditions and after injury. How this decrease occurs is not fully understood, but we hypothesized that transforming growth factor (TGF)-beta1, a cell cycle regulator that rapidly increases after injury and with age, might play a role. We found that chronic overproduction of TGF-beta1 from astrocytes almost completely blocked the generation of new neurons in aged transgenic mice. Even young adult TGF-beta1 mice had 60% fewer immature, doublecortin-positive, hippocampal neurons than wild-type littermate controls. Bromodeoxyuridine labeling of dividing cells in 2-month-old TGF-beta1 mice confirmed this decrease in neuro-genesis and revealed a similar decrease in astrogenesis. Treatment of early neural progenitor cells with TGF-beta1 inhibited their proliferation. This strongly suggests that TGF-beta1 directly affects these cells before their differentiation into neurons and astrocytes. Together, these data show that TGF-beta1 is a potent inhibitor of hippocampal neural progenitor cell proliferation in adult mice and suggest that it plays a key role in limiting injury and age-related neurogenesis.     

Brain G protein gamma subunits contain an all-trans-geranylgeranylcysteine methyl ester at their carboxyl termini.

We have shown previously that guanine nucleotide-binding protein (G protein) beta gamma complexes purified from bovine brain membranes are methyl esterified on a C-terminal cysteine residue of the gamma polypeptide. In the present study, 3H-methylated G beta gamma complexes cleaved to their constituent amino acids by exhaustive proteolysis were shown to contain radiolabeled material that coeluted with geranylgeranylcysteine methyl ester on reversed-phase HPLC and two TLC systems. Further treatment by performic acid oxidation yielded radiolabeled material that coeluted with L-cysteic acid methyl ester, verifying that the prenyl modification occurs on a C-terminal cysteine residue. Analysis by gas chromatography-coupled mass spectrometry of material released from purified G beta gamma by treatment with Raney nickel positively identified the covalently bound lipid as an all-trans-geranylgeranyl (C20) isoprenoid moiety. To delineate the distribution of this modification among gamma subunits, purified G beta gamma complexes were separated into 5-kDa (gamma 5) and 6-kDa (gamma 6) forms of the gamma polypeptide by reversed-phase HPLC. Gas chromatography-coupled mass spectrometry analyses of Raney nickel-treated purified gamma 5 and gamma 6 subunits showed that both polypeptides were modified by geranylgeranylation. These results demonstrate that at least two forms of brain gamma subunit are posttranslationally modified by geranylgeranylation and carboxyl methylation. These modifications may be important for targeting G beta gamma complexes to membranes.     

18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma

Objective  

To evaluate the usefulness of [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO)-positron emission tomography (PET) prior to the treatment of head and neck squamous cell carcinoma.     

Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer’s disease

Annals of Nuclear Medicine - A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study...