Circulating soluble Fas ligand in patients with gastric carcinoma

BACKGROUND: The Fas/Fas ligand (FasL) system is involved in cancer cell death induced by the immune system. Most of the tumors may escape the host immune attack by imitating themselves as immune-privileged sites by overexpressing FasL. FasL is synthesized as a membrane-bound protein that can be cleaved to the soluble isoform (sFasL). The objectives of this work were to determine whether the serum concentrations of sFasL in patients with gastric carcinoma were correlated with clinicopathologic features and survival rates. METHODS: The authors examined the circulating sFasL concentration in 43 healthy people and 166 primary gastric carcinoma patients at the time of diagnosis by enzyme linked immunoadsorbent assay. The results were categorized by clinical and histopathologic variables. RESULTS: The serum sFasL levels of healthy subjects were all less than 0.1 ng/mL. Among the 166 gastric carcinoma patients, the median concentration of sFasL was 0.04 ng/mL. There were no significant differences between the healthy controls and the gastric carcinoma patients group (P = 0.738). The sFasL levels were significantly increased in patients with gastric carcinoma in a manner reflective of the disease stages such as the depth of tumor invasion, lymph node metastasis, and distant metastasis. The authors determined the cutoff value (0.08 ng/mL) as a 90th percentile of healthy controls. The survival analysis demonstrated that patients with high sFasL levels had a worse prognosis than those with low levels (P < 0.001). Multivariable analysis confirmed that the sFasL concentration was an independent prognostic indicator of overall survival (P = 0.041). CONCLUSIONS: Our results indicated that sFasL concentrations could not be a new marker for early detection of gastric carcinoma but a prognostic tumor marker for the assessment of the progression of advanced gastric carcinoma.     

The Presence of CA19-9 in Serum and Saliva from Lewis Blood-group Negative Cancer Patients

Eighteen cancer patients showed high levels of CA19-9 in sera, even though the blood-group phenotypes of their red blood cells were Le(a — b —). Seven of these patients (group I) were determined as Le(a — b —) from both red blood cells and saliva consistently, whereas eleven other patients (group II) secreted either Le^a or Le^b antigen in saliva and showed the expression of incompatible Lewis blood-group antigens. GDP-fucose: N -acetyl-glucosaminide a (1 × 4)-L-fucosyltransferase was demonstrated to be present in salivas from both group I and group II. These results suggest that a cancer-associated alteration of Lewis blood-group antigen expression occurs in cancer patients.     

Neuropathology of familial amyotrophic lateral sclerosis patients with superoxide dismutase 1 gene mutation

More than 60 mutations of the copper/zinc superoxide dismutase 1 (SOD1) gene have been identified. We are aware of 19 reported autopsied cases of familial amyotrophic lateral sclerosis (ALS) linked to these mutations. A review of these cases disclosed remarkable heter-ogenicity of ALS, not only in molecular genetics but also clinicopathologically. However, it is noteworthy that all patients with alanine to valine substitution at codon 4 (A4V) mutation of SOD1 in familial ALS apparently disclose a distinct characteristic phenotype. All these patients manifested a rapid course of progressive muscular atrophy and died less than 1 year after the onset of illness. Microscopic findings were essentially identical in three cases: (i) marked loss of anterior horn neurons and Clarke's nuclei; (ii) the presence of intracytoplasmic Lewy body like hyalin inclusions and cord-like enlargements of the processes in some of the affected neurons. The Lewy body like inclusions were also recognized by antibodies to phos-phorylated neurofilaments protein, ubiquitin, and SOD1. Under electron microscopy, the inclusions consisted of a network of 10 nm neurofilaments intermingled with ill-defined coarse linear structures; (iii) degeneration of spinocerebellar tracts, and middle root zone of the posterior column.     

Anterior horn cell degeneration and Bunina-type inclusions associated with dementia

Summary The ultrastructural features of Bunina type inclusions in the anterior horn cells of a patient dying of amyotrophic lateral sclerosis with dementia appear unique. The Bunina-type inclusions are electron dense aggregates containing, and surrounded by organelle-like membranes. These inclusions appear to be a special type of autophagic vacuole, possibly arising from altered mitochondria.     

Combined paravertebral lumbar plexus and parasacral sciatic nerve block for reduction of hip fracture in four patients with severe heart failure

We experienced four cases of anesthesia for hip fracture reduction in patients with severe heart failure, where anesthesia was attempted with combined paravertebral lumbar plexus and parasacral sciatic nerve block instead of spinal anesthesia. The anesthesia was successful without any sequelae. The patients' characteristics are as follows. Case 1: 97-year-old woman with severe heart failure and old myocardial infarction. Case 2: 91-year-old man with pacemaker, heart failure and heart valve disease. Case 3: 93-year-old woman with severe heart failure and multi-vessel coronary artery stenosis. Case 4: 83-year-old woman with congestive heart failure and heart valve disease. Paravertebral lumbar plexus block was performed with Touhy needle which was directed to lumbar transverse process, then re-directed caudally. Psoas compartment was felt with loss of resistance. Twelve ml of 0.25% bupivacaine was injected. Sciatic nerve block was performed with a needle which was inserted at the midpoint between the greater trochanter and the sacral hiatus without (case 1, 2) or with nerve stimulator (case 3, 4). Eight ml of 0.25% bupivacaine was injected. During the anesthesia, propofol was injected for light sedation. Although this combined nerve block is difficult to perform compared with spinal anesthesia, this could be applicable for hip fracture reduction anesthesia, especially in patients with severe heart failure.     

Information processing flow and neural activations in the dorsolateral prefrontal cortex in the Stroop task in schizophrenic patients. A spatially filtered MEG analysis with high temporal and spatial resolution

Using a spatially filtered magnetoencephalography analysis (synthetic aperture magnetometry), we estimated neural activations in the Stroop task in nearly real time for schizophrenic patients with/without auditory hallucinations and for normal control subjects. In addition, auditory hallucinations were examined through the information processing flow of the brain neural network, including the frontal regions. One hundred unaveraged magnetoencephalography signals during the incongruent stimulus responses were analyzed with a time window of 200 ms in steps of 50 ms. In the 25-60-Hz band, cortical regions that showed significant current source density changes were examined for each time window. The three groups showed significantly decreased current source density, corresponding to neural activation, with temporal overlap along the fundamental cognitive information processing flow: sensory input system, executive control system, motor output system. Transient neural activations in the dorsolateral prefrontal cortex were bilateral with left-side dominancy for normal controls, left-lateralized for nonhallucinators and right-lateralized for hallucinators. Our results suggest that the dysfunction in the left dorsolateral prefrontal cortex was related to auditory hallucinations, while the information processing flow was unaffected in the schizophrenic subjects in the Stroop task.     

The role of electron microscopy in neuropathology

The electron microscope has been an essential instrument for elucidating the morphology of cells and tissue. Fine structural investigation of nervous tissue has disclosed numerous new findings, which were once invisible. In this communication I present my personal perspective on the role of electron microscopy in neuropathology through the presentation of selected electron microscopic projects engaged in our institution. These include brain edema, structural analysis of the myelin in the central nervous system, endodermal cysts in the central nervous system, aberrant synaptic development, toxoplasmosis in AIDS, and Hirano bodies.     

Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence

BACKGROUND AND PURPOSE: Differentiation between tumor recurrence and treatment-related brain injury is often difficult with conventional MRI. We hypothesized that the diffusion-weighted imaging (DWI) could help differentiate these 2 conditions, because water diffusion may be greater for necrotic tissues in the treatment-related brain injury than for tumor tissues in recurrence. Our aim was to analyze whether DWI findings of recurrent tumor are distinct from those of radiation necrosis. METHODS: Seventeen patients were examined prospectively. Two readers assessed the images by consensus for homogeneity and signal intensity of the lesions. Five regions of interest were drawn within the lesions on trace DWI images and apparent diffusion coefficient (ADC) maps. The minimal, maximal, and mean values of each lesion were compared between the 2 groups. Findings in 12 of 17 patients were verified histologically by surgery or biopsy; the diagnoses in the remaining 5 patients were made on the basis of follow-up MRI findings and clinical follow-up. RESULTS: There were a total of 20 lesions; 12 lesions were due to radiation necrosis and 8 lesions to tumor recurrence. In the radiation necrosis group, 8 lesions had marked hypointensity. In the recurrence group, however, no marked hypointensity was seen. The maximal ADC values within each lesion were significantly smaller for the recurrence group than for the necrosis group (P = .039). CONCLUSION: Radiation necrosis usually showed heterogeneity on DWI images and often included spotty, marked hypointensity. Significant difference was found in the maximal ADC values between radiation necrosis and tumor recurrence. DWI was useful in differentiating recurrent neoplasm from radiation necrosis.     

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis

BACKGROUND: Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains. METHODS: Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody. RESULTS: A significant difference (P <0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods. CONCLUSIONS: Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis.