Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

Immunocytochemical localization of zinc transporter 3 in the ependyma of the mouse spinal cord

We report, for the first time, the light microscopical and ultrastructural appearance of ZnT3-immunoreactivities in the ependymal cells of the central canal of the mouse spinal cord. Light microscopy revealed the presence of ZnT3-immunoreactive (Ir) ependymal cells in 1 microm thick epon sections stained by the ABC method. The ZnT3-Ir cells were observed at all levels of the spinal cord, but were a little more numerous in lumbosacral segments than in cervicothoracic segments. The ZnT3-Ir cells had large, ovoid nuclei with abundant cytoplasm, and protruded into the lumen of the central canal. Our ultrastructural findings suggest that the ZnT3-Ir ependymal cells possess secretory activity directed towards the central canal. We propose that they may play a role in the trans-ependymal mechanism responsible for zinc homeostasis between cerebrospinal fluid and the central area of the gray matter.     

Combined effects of inhaled nitric oxide and a recruitment maneuver in patients with acute respiratory distress syndrome

Nitric oxide (NO) inhalation therapy has been employed in the management of acute respiratory distress syndrome (ARDS), in order to improve oxygenation. Several factors have been implicated as being responsible for the action of inhaled NO. Alveolar recruitment methods, such as prone positioning and a sufficient positive end expiratory pressure (PEEP), have been identified as having a positive impact on the NO response. A Recruitment maneuver (RM) was introduced for the treatment of ARDS, along with a lung protective strategy. Here, we hypothesized that a RM may further augment the oxygenation of patients treated with NO inhalation. Therefore, the effects of the inhalation of NO, either in combination with a RM, or separately, were evaluated on patients with ARDS for their enhancing action. 23 patients with ARDS were enrolled, and divided into three groups. The patients in group 1 (n=11) were treated with 5 ppm NO via inhalation, followed by a RM, applying a sustained inflation pressure of 30 - 35 cmH2O for 30 seconds. Group 2 (n=6) received a RM alone, while group 3 (n=3) was treated with NO inhalation alone. The oxygenation and hemodynamic parameters were obtained prior to, and 2, 12, and 24 h after, the respective treatment procedures. For group 1, the PaO2/FiO2 increased from its initial value of 171.8 +/- 67.8 to 203.2 +/- 90.0 2 h after NO inhalation. Further improvement was noted with the continual application of the RM reaching, 215.5 +/- 74.6 (p=0.05) and 254.2 +/- 109.5 (p < 0.05), after 12 and 24 h, respectively. Initially 7 of the subjects did not respond to NO inhalation, but 3 of these non-responders changed into responders 12 h after the RM. The changes in the PaO2/FiO2 from baseline at each time period were greater in group 1 than in the other groups, but with no statistical significance. The hemodynamics of the patients was not significantly altered during the entire study period. We conclude that the combined application of NO inhalation and a RM could be beneficial and safe for patients with ARDS, showing an enhancing effect in improvement of oxygenation.     

Presence of immunoglobulin M antibodies around the glomerular capillaries and in the mesangium of normal and passive Heymann nephritis rats

Summary Diffuse distribution of small, faintly staining, beaded deposits of rat immunoglobulin M (IgM) around the glomerular capillary blood vessels, and a more intensely staining larger deposition in the mesangium, were observed on the kidney sections of normal rats. As glomerular-fixed nephritogenic antigens are known to be present on the epithelial aspect of the glomerular basement membrane (GBM), especially at the soles of foot processes and at the slit pores, it was assumed that the IgM antibodies were directed against these antigens. Investigation by immunofluorescent antibody double-staining techniques of rat kidney sections obtained from normal and rabbit anti-FX1A-injected rats stained for the nephritogenic antigen showed that a number of antigenic sites in the glomeruli and in the mesangium shared antibody hits by heterologous rabbit IgG and autologous rat IgM antibodies. Most sites in the glomeruli stained specifically for rat IgM or rabbit IgG, but preferentially for the latter. The intensely fluorescent mesangial deposits stained mainly for rat IgM, indicating that at these sites the antigenic material was virtually saturated, while areas at the entry to the mesangial space also stained for rabbit IgG, indicating that at these locations free nephritogenic epitopes were still available for reaction with the anti-FX1A antibody. Western blot analysis have shown that the rabbit anti-rat FX1A IgG and the rat anti-rat KF3 IgM antibodies are directed against the same renal tubular-derived antigen with a molecular weight of 70,000. These experimental findings collectively demonstrate that the heterologous IgG and autologous IgM antibodies are directed against the same nephritogenic antigen, which is found in the glomeruli, the mesangium and the proximal convoluted tubules. Thus, the IgM autoantibody has a possible physiological role but, in addition, there is evidence of active immunophagocytic events, manifested in a rapid and continuous entrapment and expulsion of macromolecules after their processing by the mesangial cells of normal and passive Heymann nephritis rats.     

Radiation-induced lung injury in vivo: Expression of transforming growth factor—Beta precedes fibrosis

Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF), a fibrogenic and radiation-inducible cytokine, was studied from 1–16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF protein in bronchoalveolar lavage (BAL) fluid peaking at 3–6 weeks as compared to sham-irradiated control rats. Steady state TGF mRNA expression as shown by whole lung northern blot assay paralleled the TGF protein expression in BAL fluid. The peak of TGF protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8–10 weeks after irradiation. In conclusion, TGF and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.     

Additive Antinociception between Intrathecal Sildenafil and Morphine in the Rat Formalin Test

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 µL of 5% formalin solution was applied to the hind-paw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.     

Spontaneous disruption of mycotic aneurysm involving innominate artery

We report a case of ruptured mycotic aneurysm involving innominate artery requiring an urgent surgical treatment. A 62-yr-old woman presented with fever and dyspnea. Previously, she was diagnosed with colon cancer and received right hemicolectomy and one cycle of adjuvant chemotherapy. On echocardiogram, pericardial effusion was noted and emergency pericardiocentesis was performed. CT scan revealed aortic aneurysm involving ascending aorta and innominate artery, and thrombi surrounding those structures. Patch repair of the defect in the ascending aorta and ringed Goretex graft to bypass the innominate and ascending aorta were performed. We believe that this is the first case of ruptured mycotic aneurysm involving innominate artery.     

Synthesis and characterization of polyanhydride for local BCNU delivery carriers

p-Carboxyphenoxy propane (CPP) prepolymer consisting of 4 units and sebacic acid (SA) prepolymer consisting of about 10 units were synthesized by reacting CPP and SA in the presence of excess acetic anhydride, respectively. Polyanhydride, poly(CPP-SA) copolymers were copolymerized by a melt polycondensation process with a mixture of CPP and SA prepolymer. Copolymers of average molecular weight up to 110,000 g/mol were achieved. The crystallinity of poly(CPP-SA) copolymers was decreased by the addition of the CPP homopolymer segment to SA homopolymer. Poly(CPP-SA) copolymers gradually degraded for period of 10 days. No large difference of weight loss observed according to molecular weight variation of poly(CPP-SA) copolymers. BCNU release from wafers fabricated by poly(CPP-SA) showed a sustained release pattern with no initial burst and delay of drug release.     

Modulation of transglutaminase expression in rat skeletal muscle by induction of atrophy and endurance training.

The persistence of muscle fiber number regardless of size reduction in muscle atrophy has not yet been fully explained. For the mechanism inherent in skeletal muscle tissues for preventing cellular death, the protective function of muscle tissue through transglutaminases has been tested, since the enzyme is responsible for structural stabilization and participates in signal transduction. In the present experiment, hindlimb suspension for two weeks caused a marked muscle atrophy in Wistar female rats. Comparison of muscle weight and histological analysis showed that suspension-induced atrophy in the hindlimb was more prominent in the soleus muscle, comprised mainly of type I fiber than that in the plantaris muscle of type II fibers. The immunohistochemical analysis with antitransglutaminase C antibody (anti TGase C Ab) showed that some atrophic bundles of soleus muscle were positively reacted with the antibody. The anti-TGase C Ab-reactive substances were observed to disappear significantly after endurance exercise, indicating their characteristic atrophy-dependency. The enzymatic analysis of transglutaminase showed the increase in activity in the atrophic soleus muscle tissue, compared with that in the normal or exercise-trained muscle tissues. From these results, the expression of TGase in the atrophic muscle is suggested to be the possible marker for muscle atrophy and its expression is probably related with the protective mechanism of the muscle tissue to prevent further cellular damage in the atrophic process.     

Action naming with impaired semantics: Neuropsychological evidencecontrasting naming and reading for objects and verbs

We contrast naming from pictures, and reading words, for objects and verbs (actions relating to the objects) in a patient with a large, posterior left-hemisphere lesion. We present evidence for spared picture naming for verbs relative to objects, whilst the opposite pattern of sparing occurred in reading. Objects were also spared relative to verbs in tasks requiring that written words be matched to either pictures or auditory words, in the presence of semantically related or unrelated distractors. We conclude that verb semantics were more impaired than semantic knowledge for objects, and that the better semantic knowledge for object names supported word reading. With pictures, however, action verb retrieval was maintained through a nonsemantic route from vision to action, or though preserved right-hemisphere "action semantics."