Significance of Development and Reversion of Collaterals on MRI in Early Neurologic Improvement and Long-Term Functional Outcome after Intravenous Thrombolysis for Ischemic Stroke.

BACKGROUND AND PURPOSE: Predicting response to rtPA is essential in the era of endovascular therapy for stroke. The purpose of this study was to elucidate prognostic factors of early neurologic improvement and long-term outcome with respect to the development and reversion of leptomeningeal collaterals in recanalization therapy after acute ischemic stroke. MATERIALS AND METHODS: We analyzed consecutive patients with proximal MCA occlusion treated with rtPA from 2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain MR imaging before rtPA. To assess the reversion of collateral signs, we included patients who underwent follow-up MR imaging. We assessed the development and reversion of collaterals by using a combination of 2 MR imaging collateral markers, the hyperintense vessel sign and the posterior cerebral artery laterality sign. Early neurologic improvement was defined as a decrease in the NIHSS score of ≥10 or a score of ≤2 at 24 hours of treatment. RESULTS: Early neurologic improvement was observed in 22 of 48 eligible patients. The development of collaterals at arrival (15/22 versus 9/26, P = .042) was significantly associated with early neurologic improvement. Multivariate analysis adjusting for other variables showed that the development of collaterals at arrival (OR, 4.82; 95% CI, 1.34-19.98; P = .015) was independently associated with early neurologic improvement. Reversion of collaterals was significantly associated with successful recanalization (P < .001), and multivariate analysis showed that the reversion of collaterals was an independent prognostic factor of long-term functional outcome (OR, 5.07; 95% CI, 1.38-22.09; P = .013). CONCLUSIONS: Our results indicate that the development of leptomeningeal collaterals plays a crucial role in achieving early neurologic improvement, and reversion of collaterals predicts a favorable outcome via arterial recanalization after rtPA treatment for acute stroke.

Distinguishing patients with senile dementia of Alzheimer type and normal elderly subjects utilizing xenon CT-CBF and multivariate analysis.

Local cerebral blood flow (LCBF) was measured in 17 patients with senile dementia of Alzheimer type (SDAT) and 17 normal controls, utilizing stable xenon computed tomography (Xe CT-CBF). In patients with SDAT, LCBF values were decreased in the cerebral cortex and subcortical structures including the thalamus, basal ganglia and white matter of both hemispheres. Linear discriminant function analysis of LCBF values separated patients with SDAT from normal elderly subjects, with an error of 8.8%. Variables helpful in distinguishing SDAT patients from normal subjects were LCBF values for the frontal and temporal cortex. Multiple regression equation for predicting cognitive performance scores from LCBF values showed the best correlations with LCBF values for the frontal and occipital cortex and thalamus. Xe CT-CBF measurements provide useful information concerning diagnosis and brain function in patients with SDAT.

Acute Wernicke's encephalopathy: comparison of magnetic resonance images and autopsy findings.

This is the first report of acute Wernicke's encephalopathy in which characteristic magnetic resonance (MR) findings have been verified by postmortem histopathological examination. The high-signal areas surrounding the third and the fourth ventricles and the aqueduct on the T2-weighted images reflected the spongy disintegration of the neuropil, which is the typical pathological finding in Wernicke's encephalopathy. We confirmed that MR imaging is essential to the early diagnosis of Wernicke's encephalopathy.

[Proton MR spectroscopy findings in herpes simplex encephalitis].

Localized proton magnetic resonance spectroscopy (1H-MRS) was conducted in two patients with herpes simplex virus type I encephalitis (HSE). MR spectra of bilateral temporal lobes were acquired by the single voxel method using 1.5T unit. Peaks indicating N-acetyl aspartate (NAA), choline (Cho) and creatine including phosphocreatine (Cr) were identified and ratios of NAA/Cr and Cho/Cr were calculated. These ratios were compared with those of the contralateral side showing normal MRI findings and also with the control spectra obtained from normal volunteers. Three abnormal findings were observed in the spectra of the patients suffering from HSE; 1. significant reduction of the NAA/Cr ratio at the involved temporal lobe, 2. mild reduction of the NAA/Cr ratio at the normal temporal lobe, and 3. elevation of the Cho/Cr ratio at the bilateral lobes, but more significant on the involved sides. These results indicated that neural loss and gliosis occurred in the contralateral area with normal MR images as well as the involved hemisphere. We concluded that 1H-MRS is able to show the specific histological findings of herpes simplex encephalitis. This is the first report assessing 1H-MRS for patients with HSE in Japan.

[Cerebral metabolic disturbance in hypoxic encephalopathy: evaluation with H-1 MR spectroscopy].

PURPOSE: To analyze metabolic changes in the brain during hypoxic encephalopathy. MATERIALS AND METHODS: MR imaging (MRI) and H-1 MR spectroscopy (H-1 MRS) were performed on three patients with hypoxic encephalopathy, who had need temporary mechanical ventilation, and five healthy age-matched volunteers. Spectra were obtained from bilateral fronto-parietal gray matter and basal ganglia voxels. N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) were analyzed. RESULTS: (1) MRI; T1 weighted MRI revealed high signal intensity areas in the diffuse cerebral cortex and basal ganglia in two patients. The former was thought to reflect cortical laminar necrosis. T2-weighed MRI showed high signal intensity in diffuse white mate. (2) H-1 MRS; significant reduction of the NAA/ Cr ratio and elevation of the Cho/Cr ratio were detected. CONCLUSION: H-1 MRS is able to quantify metabolic alterations in the hypoxic encephalopathy.

Interleukin 4 (IL-4) blocks the IL-2-induced increased in natural killer activity and DNA synthesis of decidual CD16-CD56bright NK cells by inhibiting expression of the IL-2 receptor alpha, beta, and gamma.

The natural killer (NK) activity and DNA synthesis of decidual CD16-CD56bright NK cells were markedly elevated by treatment with interleukin 2 (IL-2). IL-4 did not affect NK activity or DNA synthesis of decidual CD16-CD56bright NK cells, but inhibited the IL-2-induced NK activity and DNA synthesis in a dose-dependent manner. Flow cytometry of decidual mononuclear cells cultured in IL-2 or IL-4 or both IL-2 and IL-4 demonstrated IL-4 inhibition of the expression of the IL-2 receptor alpha (IL-2R alpha), IL-2R beta, and IL-2R gamma on decidual CD16-CD56bright NK cells. This suggests that IL-4 blocks the IL-2-induced NK activity and DNA synthesis of decidual CD16-CD56bright NK cells by inhibiting the expression of IL-2R alpha, IL-2R beta, and IL-2R gamma.

Expression of the interleukin-2 receptor gamma chain on cord blood mononuclear cells.

Lymphocytes in umbilical cord blood and neonatal peripheral blood have been shown to have less ability in an immune reaction. In our present experimental approach to address this issue, we made use of the cord blood of full-term birth infants to investigate the expression of the interleukin- 2 receptor gamma (IL-2Rgamma) chain that is shared with receptors for IL-4, IL-7, IL-9, and IL-15 as well as IL-2. The gamma chain expression in cord blood lymphocytes was about one-third that in the lymphocytes of adults, whereas no significant difference between cord blood and adult monocytes was observed. A reduced expression of the gamma chain was observed in all of the CD4+ T cells, CD8+ T cells, gamma-delta T cells, B cells, CD16+ natural killer (NK) cells, and CD56(bright) NK cells of the cord blood lymphocytes. The reduced gamma chain expression reached two-thirds of that in adults after 3 days of culture in vitro and in infants 3 days after birth, thus implying that the increase in the gamma chain may significantly contribute to the prevention of neonatal infection.

[The viewpoints of viral vertical transmission from fetal neonatal immunologic aspects].

A. The development of fetal Immune system 1. Complement: Alternative pathway is dominant in the development of fetal complement. 2. Neutrophil function: Phagocytosis in full term infants was increased to be adult-level, but bactericidal function was decreased. 3. NK activity: NK activity in full-term infants was significantly lower than in adults, however, IL-2-augmented NK activity did not indicate any significant difference with levels in adults. In pre-32 week infants both NK and IL-2-augmented NK activity were further decreased as opposed to in full-term infants. 4. LAK activity: LAK activity was fully developed already in 19 week infants, indicating that auto-monitoring of mutant cells is already under control from the early stages of fetal development. 5. Antibody production: Antibody production in infants was significantly decreased in comparison to adults. Reduced cytokine (IL-1, BCDF) production were considered to be the causal factors. 6. IL-2, IL-2R: In IL-2 production, no difference was recognized between normal neonates and adult subjects. In contrast, a significantly higher value of IL-2 production was observed for premature neonates born between 16 and 36 GW, compared with adults. IL-2 production and IL-2R system is fully developed at 22 weeks. 7. BCDF gamma, BCDF mu: Reduced compared to that of adults. 8. IL-6, IL-8, G-CSF: Much higher levels were found in cases of intrauterine infection, particularly in cases of premature delivery. The cytokine levels were 20-to-30-fold higher in chorioamnitis-positive premature delivery group. 9. M-CSF: M-CSF is increased, M-CSF may play a role in decidual function and placental function by the autocrine and paracrine system. 10. IL-1 alpha, IL-1 beta, IL-6: These production by macrophages was diminished in aborted fetuses, premature infants and IUGR infants. However, in the infants of mother with intrauterine infection, cytokine production was elevated to the level in full term infants and adults. 11. IFN gamma: Production of IFN gamma by memory T cells was diminished in premature infants. B. The vertical transmission of HTLV-I. The routes of vertical transmission of HTLV-I are intrauterine, intra-birth canal and via breast milk. Bottle-feeding is an effective way of avoiding mother-to-child infection. However breast milk is necessary for optimal infant nourishment, so we use -20 degrees C for 12 hours freeze-thawing of breast milk.(ABSTRACT TRUNCATED AT 400 WORDS)

Identification of macrophage colony-stimulating factor in human milk and mammary gland epithelial cells.

Human milk contains cellular and soluble host-protective components. Macrophages in human milk constitute a major cellular component in contrast to those in the peripheral blood. We have investigated a mechanism of local expansion of macrophages in human milk. First, biologically active macrophage colony-stimulating factor (M-CSF) was identified in human milk. The maximal concentrations of M-CSF in human milk were 10- to 100-fold higher than those in the serum. The concentrations of M-CSF in the milk had no correlation with those in the serum. M-CSF was immunohistochemically detected in the epithelial cells of the ducts and alveoli of the mammary gland. In situ hybridization study confirmed the local synthesis of M-CSF in the mammary gland epithelial cells. A possible role of female sex steroids was discussed in the regulation of M-CSF production by mammary gland epithelial cells.

Hepatocyte growth factor promotes the growth of cytotrophoblasts by the paracrine mechanism.

Both placental and decidual tissues contained extractable HGF, the former HGF level (31.4 +/- 23.4 ng/mg total protein) being approximately 30 times the latter HGF level. When the localization of HGF protein and HGF mRNA in placental tissues was examined by immunohistological staining and in situ hybridization, HGF protein and HGF mRNA were detected in the mesenchymal cells of the placenta, but were absent in the cytotrophoblast and syncytiotrophoblast. Although c-met protein was expressed in the cytotrophoblast, this receptor was not detectable in the syncytiotrophoblast by immunohistochemical methods. c-met mRNA was detected in placental cell line (tPA30-1) and 4 choriocarcinoma cell lines (BeWo, Jar, Jeg-3, and NUC-1), but HGF mRNA was absent in these cells. When cytotrophoblast cells were cultured in a serum-free medium in the presence of HGF, their DNA synthesis was enhanced depending on the HGF concentration, although human placental lactogen secretion itself was not affected by HGF. These results demonstrated that HGF promotes the growth of the cytotrophoblast by the paracrine mechanism, although it does not serve as a placental differentiation factor.

Detection and localization of interleukin-8 mRNA and protein in human placenta and decidual tissues.

It has been reported that interleukin-8 (IL-8) is secreted from the placental and decidual tissues and that IL-8 levels in the amniotic fluids are significantly elevated by chorioamnionitis or labor pain. The present study was aimed at defining the localization of IL-8 mRNA as well as IL-8 protein at the feto-maternal interface using in situ hybridization and immunohistochemical staining. Both IL-8 mRNA and protein were localized in cytotrophoblast, syncytiotrophoblast and Hofbauer cells of the placenta, decidual stromal cells, decidual lymphocytes and endometrial gland cells. IL-8 secretion from glandular cells has not previously been reported. In addition, we confirmed IL-8 mRNA expression and secretion of IL-8 by an endometrial cancer cell line (Ishikawa) using the reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods, respectively.

Localization of stem cell factor (SCF) and c-kit mRNA in human placental tissue and biological effects of SCF on DNA synthesis in primary cultured cytotrophoblasts.

The supernatant of homogenized human placental tissues at early and late stages of pregnancy were found to contain 40-100 pg of stem cell factor (SCF)/mg of total protein by enzyme linked immunosorbent assay. When the SCF mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), the secretory type and membrane-bound type SCF mRNA were detected in the human placental tissues in the early stages of pregnancy and in a human placental cell line;tPA30-1 cells. However, the secretory type SCF mRNA was predominant and membrane-bound type SCF mRNA was absent or very weak in the term placental tissues. When the distribution of SCF mRNA and c-kit mRNA in the placental tissues was examined by in situ hybridization, SCF mRNA was detected in the cytotrophoblast, the intermediate trophoblastic cell column and the stromal cells, while c-kit mRNA was detected in the cytotrophoblast and the intermediate trophoblastic cell column. Both c-kit and SCF mRNA were absent or very weak in the syncytiotrophoblasts. The supernatant of primary cultured cytotrophoblasts and tPA30-1 cells were found to contain SCF. In cytotrophoblasts in the early stage of pregnancy cultured in the presence of recombinant human secretory type SCF, DNA synthesis was increased depending on the SCF concentration. These findings indicate that SCF is a cytokine which promotes the growth of placental cells by the autocrine and paracrine mechanism.

Expression of recombinase-activating genes (RAG-1 and 2) in human decidual mononuclear cells.

Recombinase-activating genes (RAG-1 and RAG-2) are expressed in immature T or B lymphocytes and possess activity to induce V(D)J rearrangement in TCR and Ig genes. We examined their expression in human decidual and non-pregnant endometrial samples using a highly sensitive RT-PCR technique. Expression of RAG-1 and 2 was noted in all (13/13) pregnant decidual tissues obtained at different gestational stages. After anti-human Ig treatment to rule out the possibility of RAG-1,2 expression from decidual B-cells, strong expression of RAGs was still noted in B cell depleted decidual cells in contrast to lymph nodes and PBMC that lost RAG mRNA expression after this treatment. After FACS mediated cell sorting, strong expression of RAG-1,2 was noted in CD16-CD56bright cells and weak expression in CD3+ cells. Although CD16-CD56bright cells lack surface CD3, they express CD3 epsilon mRNA only detectable by RT-PCR. Our results suggest the nature of decidual CD16-CD56bright cells as a progenitor of extrathymic T cells that possess RAG-1 and 2 mRNA as markers of their immaturity, and possibly differentiate into CD3+ extrathymic T-cells in the decidua under the influence of trophoblastic cells. We propose the human decidua as a new site of extrathymic T-cells differentiation and propose possible roles of trophoblastic cells to attract progenitor lymphocytes of bone marrow origin and trigger their TCR rearrangement as thymic epithelial cells.