Immunoregulatory effects of phospholipase A2 (PLA2) on the proliferation of human lymphocytes

Extracellular phospholipase A2 (PLA2) is a proinflammatory enzyme found especially in the inflammatory exudate to modulate blood flow to areas of antigen stimulation. In this study we found that PLA2 exerted a biphasic effect on the proliferation of phytohemagglutinin (PHA)-stimulated human mononuclear cells (PHA MNC). At low concentrations range from 0.001 to 1 U/ml, PLA2 enhanced the proliferation of PHA MNC (maximal increase was 37.0 +/- 5.67%). Conversely, at concentrations over 10 U/ml, PLA2 markedly suppressed the PHA-induced MNC proliferation (maximal decrease was 88.86 +/- 2.89%). PLA2 was non-toxic to lymphocytes after three days culture, unless the concentration was higher than 100 U/ml. The membrane polarization of PHA-stimulated lymphocytes was also increased by PLA2 at a low concentration. In addition, PLA2 displayed a similar effect on the proliferation of streptokinase-streptodornase (SK/SD) or allogeneic cell stimulated lymphocytes. The change of lymphocyte proliferation by PLA2, was parallel to the change of percentage of helper T cells. Furthermore--a CD4-rich population was proved more susceptible to PLA2 effect than a CD8-rich population. Para-bromophenacyl bromide (pBPB), an irreversible inhibitor of PLA2, abrogated the biphasic effect of PLA2 on PHA MNC proliferation. These results suggest that PLA2 plays a regulatory role on immune reactions by modulating the percentage of helper T cells.     

Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal

It is often difficult to make a clinical or histologic diagnosis of erythrodermic mycosis fungoides (MF) and Sézary syndrome (SS). Whereas the histologic parameters for making a diagnosis of MF with well-developed patch and plaque stage lesions are clearly defined, the same criteria appear to be less relevant for diagnosing MF in patients with erythroderma secondary to the disease. In order to better define the histologic features of erythrodermic MF and SS, we studied 28 routine histologic sections of 17 patients with known erythrodermic MF or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24 parameters was scored semi-quantitatively and the data were compared to data previously reported from a group of 64 patients with limited patch and plaque stage lesions of MF. When compared to biopsies from patients with limited patch/plaque lesions, biopsies taken from erythrodermic patients displayed more parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045), fewer hyper-convoluted cells in the epidermis, more dermal hyperconvoluted cells (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent teleangiectasias (p=0.0028) and more mitotic figures.
The histologic features of erythrodermic MF and Sézary syndrome are even more subtle than the features of patch and plaque stage MF, thus rendering the histologic diagnosis more difficult.     

Juvenile Xanthogranuloma on the Palm

Abstract: Juvenile xanthogranuloma is a xanthomatous and granulomatous condition that frequently arises before 1 year of age and mainly occurs on the head and trunk. We report a rare solitary juvenile xanthogranuloma on the right palm of a 10-year-old girl, present for one year. This solitary involvement of the palm has been reported only twice before.     

Antitumor activity of five new platinum complexes having a glycolate leaving ligand.

In an attempt to develop a new anticancer platinum complex with greater or equivalent antitumor activity but reduced side effects compared with cisplatin (CDDP), a series of new platinum complexes having a glycolate leaving ligand was synthesized. Among them, five complexes were selected for further development on the basis of adequate water solubility, low nephrotoxicity and high antitumor activity in a murine system. The chemosensitivity of these five complexes was examined in MTT assay against two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and two human stomach adenocarcinoma cell lines, MKN-45 and KATO III. Their IC50 and relative antitumor activity (RAA) values were compared with those of CDDP and 254-S, a second-generation platinum complex with a glycolate leaving ligand under phase III clinical trial. The lowest mean IC50 value was observed in CDDP, followed by SKI 2034R and SKI 2033R. In this study, the antitumor activity was evaluated in terms of RAA values and SKI 2034R showed the highest RAA value. The order of RAA values was SKI 2034R > CDDP > SKI 2032R > SKI 2033R > SKI 2030R > SKI 2029R > 254-S. Based on the RAA order, we have recommended SKI 2034R as the most promising candidate for further development of a clinically useful platinum complex.     

Cyclosporine overcomes cold preservation/reperfusion injury of liver graft: Chemokine release and liver ultrastructure

There is a growing body of evidence that the cytokine, tumor necrosis factor-α (TNF-ga), plays an important role in the development of hepatic ischemia/reperfusion injury. We found that the immunosuppressants, cyclosporine-A (CsA), azathioprine, and FK506, have protective effects on such injury. The purpose of the present study was to elucidate mechanisms involved in these beneficial effects of the immunosuppressant, CsA, on liver injury following cold preservation and transplantation, with special reference to the suppression of TNF-α release. Rat livers were stored in Euro-Collins solution (EC) at 4°C for 6h and orthotopically transplanted. The animals allotted to two groups: group A (untreated controls) and group B (CsA pretreatment of recipients). CsA (10 mg/kg, p.o.) was given for 3 consecutive days preoperatively. CsA pretreatment of the recipients significantly improved the 2-week survival rate (0/6 for group A, 3/6 for group B;P<0.05) and this was associated with a significant decrease in serum TNF-α levels 2h posttransplantation (group A, 69.8±15.7 pg/ml; group B, 22.8±6.8; mean±SEM;n=12 each;P<0.05) and amelioration of sinusoidal endothelial injury, assessed by electron microscopy. Plasma endotoxin levels following reperfusion of the grafts were not altered by the CsA therapy. Morphologically, CsA pretreatment of the recipients did not alter activation of Kupffer cells. CsA pretreatment of the recipient aids in preventing cold preservation/reperfusion injury of the liver graft, possibly by modulating effects of TNF-α.     

Endothelin and cyclosporine nephrotoxicity.

Although some humoral and neural factors have been implicated in the persistent vasoconstriction characterizing many forms of acute renal failure, the mechanisms for this abnormal vascular function have remained largely unresolved. Several factors previously postulated to have a role in acute renal failure have been shown to enhance endothelin (Et) production or gene expression. We studied the potential pathophysiologic role for Et in several models of acute renal failure, including postischemia, endotoxin, and cyclosporine (Cy) nephrotoxicity. We have found that, in vivo, Cy (and also endotoxin) elevates circulating Et. We further showed that antagonizing Et's action with Et antibody ameliorates renal vasoconstriction following renal ischemia, Cy, and endotoxin administration. Additionally, our studies showed that even after circulating levels of Et decrease (following Cy), there is upregulation in Et receptors in the kidneys. Overall, endothelin appears to feature prominently in the pathophysiologic processes occurring during several forms of acute renal failure.     

Embryology of the human fetal hippocampus: MR imaging,anatomy, and histology.

PURPOSETo identify changes in the embryology of the hippocampus responsible for its adult anatomy.METHODSTen human fetal specimens ranging from 13 to 24 weeks'' gestational age were examined with MR imaging. Dissections and histologic sections of 10 different specimens of similar ages were compared with MR imaging findings.RESULTSAt 13 to 14 weeks'' gestation, the unfolded hippocampus, on the medial surface of the temporal lobe, surrounds a widely open hippocampal sulcus (hippocampal fissure). At 15 to 16 weeks, the dentate gyrus and cornu ammonis have started to infold. The hippocampal sulcus remains open. The parahippocampal gyrus is larger and more medially positioned. The CA1, CA2, and CA3 fields of the cornu ammonis are arranged linearly. The dentate gyrus has a narrow U shape. By 18 to 20 weeks, the hippocampus begins to resemble the adult hippocampus. The dentate gyrus and cornu ammonis have folded into the temporal lobe. The hippocampus and subiculum approximate each other across a narrow hippocampal sulcus. The CA1-3 fields form an arc and the CA4 field has increased in size within the widened arch of the dentate gyrus.CONCLUSIONMR imaging of fetuses provides a developmental basis for understanding hippocampal anatomy.     

RETT's syndrome in Korea--report of two cases

Rett's syndrome(RS) is a progressive neurodegenerative disorder characterized by exclusive occurrence in females, autistic behavior, dementia, gait ataxia, loss of purposeful use of the hands with stereotypic hand movement, and seizures. Initially RS was considered to be very rare; however, recent reports suggest that the prevalence is considerably higher and occurrence is world-wide. Because the pathophysiological process remains unknown, the diagnosis of RS is based mainly on its characteristic clinical features and course. We experienced two cases of RS which, to our knowledge, are the first reported in Korea. It is quite possible that many patients with RS not yet being diagnosed in Korea.     

Pure sensory stroke. Clinical-radiological correlates of 21 cases.

BACKGROUND: Although pure sensory stroke is a relatively common lacunar syndrome, the responsible lesions are often unidentified because of their small size. I reported 21 cases of pure sensory stroke in which the lesions could be identified by head computed tomography and/or magnetic resonance imaging and correlated the clinical findings with the radiological lesions. SUMMARY OF REPORT: Eleven patients had thalamic strokes. Lacunes confined to the posterolateral part of the thalamus were found in nine cases, and hemorrhages of relatively large size were found in two. Five patients showed a loss of all sensory modalities, but six with very small lacunes showed minor or restricted sensory changes. Seven patients with lacunes or hemorrhages in the lenticulocapsular region or corona radiata showed abnormalities of spinothalamic tract sensation. Two patients with a small lacune and a hemorrhage in the pontine tegmentum showed a selective sensory deficit of the medial lemniscal type. One patient with a small cortical infarct showed a cortical sensory loss that was preceded by cortical sensory transient ischemic attacks. CONCLUSIONS: Pure sensory stroke can occur with lesions in various areas of the somatosensory system. Hemisensory deficits of all modalities usually are associated with a relatively large lacune or hemorrhage in the lateral thalamus, whereas tract-specific or restricted sensory changes suggest very small strokes in the sensory pathway from the pons to the parietal cortex.