Postmortem Diagnosis of Acute Megakaryocytic Leukemia Usefulness of lmmunohistochemistry and Tissue Hemogram

An autopsy case of acute megakaryocytic leukemia (AMKL) is presented. The bone marrow was hypercellular with proliferation of three lineages, especially megakaryocytes. Immunohistochemical examination revealed many platelet glycoprotein IIb/IIIa (GP IIb/IIIa)- positive blast cells in bone marrow. The proportion of the blasts was 26.4% by tissue hemogram. GP IIb/IIIa-positive blasts and megakaryoblasts were deposited massively in lymph nodes. lmmunohistochemistry against GP IIb/IIIa and tissue hemograms by paraffin section are needed to diagnose AMKL by postmortem examination, since the identification of ultra-structural platelet peroxidase in autopsy materials is difficult.     

Brain mapping analysis in patients with hepatic encephalopathy

Summary Topographical analysis of cerebral electrical activity was performed in 44 patients with hepatic encephalopathy. These patients were classified in 5 groups according to clinical criteria. Eight healthy subjects were used as a control group. All were studied in an awake, eyes closed, condition and some [Control Group (CG), Group 0 (G0), Group 1 (G1) and Group 2 (G2)] also in an awake, eyes open, condition. The awake, eyes closed, maps showed marked differences in the power spectral density (PSD) of the different bands, when comparing normal subjects with patients with several degrees of hepatic encephalopathy. These differences were related to the degree of clinical involvement, mainly in the alpha and delta PSD bands. The combination of a decreased alpha PSD, increased delta PSD, and decreased mean dominant frequency (MDF) allowed a clear discrimination between the different clinical groups. The differences observed between awake, eyes closed, and awake, eyes open, conditions were especially helpful to discriminate between CG subjects and G0, G1 and G2 patients.     

FK506 (tacrolimus) improves lung injury through inhibition of Fas-mediated inflammation

Objective To investigate whether FK506 (tacrolimus) can inhibit Fas- or A23187-induced interleukin (IL)-8 expression and cell death in A549 human alveolar epithelial cells, plus Fas-mediated acute lung injury in vivo. Methods Assays for IL-8, cell death, and caspase-3 activity were performed. A549 cells were treated with 25 μmol A23187 or 0.2 μg/ml agonistic anti-Fas antibody plus 5 ng/ml interferon-gamma (IFN-γ). Tacrolimus was treated at 0.1–10 ng/ml. For in vivo experiment, agonistic anti-Fas antibody (Jo2) at 2.5 μg/g was intratracheally instilled into C57BL/6 mice. Neutrophils and protein contents in bronchoalveolar lavage (BAL) fluid were measured within 24 h of instillation. Mice were orally treated with 32 mg/kg of tacrolimus 24 h and 1 h prior to instillation. Results Both Fas and A23187 caused significant IL-8 expression and cell death in A549 cells. Tacrolimus inhibited A23187-induced IL-8 expression alone while it protected all Fas-mediated responses. Mice instilled intratracheally with Jo2 at 2.5 μg/g had significant increases in neutrophils, protein contents in BAL fluid and in expression of chemoattractants for neutrophils. These increases were reversed by tacrolimus. Conclusions Tacrolimus serves as a therapeutic option for improving lung injury through inhibition of Fas-mediated inflammation. Received 7 November 2005; returned for revision 28 December 2005; accepted by G. Wallace 2 February 2006     

Age-Related Changes in Ceruloplasmin Content in W/SSM Rats

We studied enzyme systems (lactate dehydrogenase) of mitochondria in cerebral nerve cells in experimental encephalopathy developing after thermal injury. In animals receiving neuromedin at the early terms after injury, the ratio of forward to reverse lactate dehydrogenase reactions significantly increased over the first day after injury and returned to normal on day 7. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 626–627, June, 2008     

Ultrastructural myeloperoxidase activity and expression of myeloid-associated antigens in acute lymphoblastic leukemia

Ultrastructural myeloperoxidase (MPO) activity and myeloid-associated antigen (MyAg) expression were investigated in 12 adult patients with acute lymphoblastic leukemia (ALL). Ultrastructural MPO was detected by 3 different methods. Immunophenotyping was performed by flow cytometry, using a series of monoclonal antibodies. Ultrastructural MPO-positive blast cells were detected in 6 patients (50%). In 5 of these 6 patients, the methods detecting both MPO and platelet peroxidase (PPO) activities found MPO-positive blast cells more frequently than those detecting MPO activity alone. In 2 patients (17%), at least one kind of MyAg was positive. Ultrastructural MPO activity was detected more frequently than MyAg expression in ALL patients. This method of detecting PPO and MPO is recommended for detection of ultrastructural MPO-positive ALL.     

Defective Treg response in acute kidney injury was caused by a reduction in TIM-3+ Treg cells

Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.

Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.

Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.

Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies.     

Case report: human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient

Previous studies have suggested a neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV-7). In this report, a case of fatal encephalitis is described and its association with HHV-7 infection is discussed. An 8-year-old girl received a peripheral blood stem cell transplant for relapsed acute lymphoblastic leukaemia. The post-transplant period was uneventful and a course of intrathecal chemotherapy was given on Day-30. On Day-41, she developed acute encephalopathy with diplopia and nystagmus. She ran a rapid downhill course and succumbed despite antiviral treatment. The only positive pathological finding was the multiple microscopic foci of haemorrhage associated with neuronal degeneration detected in the brain stem. All microbiological investigations were negative, except for the presence of HHV-7 DNA in cerebrospinal fluid and brain stem tissue samples.     

Pneumonien bei akuten Leukämien

Summary Acute leukaemia was complicated by pneumonia in 38 (34.8%) of 109 patients treated between 1979 and 1983; in 39.5% of the patients pneumonia occurred more than once. In 23 patients (60.5%) pneumonia occurred during cytostatic therapy, and 25 patients (65.8%) had less than 1000 mm² granulocytes. Antibiotic therapy had no or only little effect in 70%. A total of 21 patients (55.3%) died of pneumonia. In 15 patients a direct relationship could be seen between pneumonia and the bacterial spectrum in the sputum. A prevalence of gram-negative bacteria was found (24 of 40 bacteria isolated, especially Enterobacteriaceae (19). Fungi were cultivated in 10 cases. Each of the typical pneumonia bacteria was only seen once respectively. It is most important that therapy begin immediately, even before the bacteria have been identified. Only then is there hope that the survival time of patients with acute leukaemia can be influenced.

     

Neuropathology of the Central Nervous System in Acquired Immune Deficiency Syndrome (AIDS) in Japan

The neuropathologiesl features of the central nervous system in IS autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.