Two-year outcome of first-line antiretroviral therapy among HIV-1 vertically-infected children in Hanoi, Vietnam.

A retrospective analysis of 86 HIV-1 vertically-infected Vietnamese children with a follow-up period >24 months after initiating antiretroviral therapy (ART) was performed from 2008 to 2012, to assess the outcome of first-line ART in resource-limited settings. Of the 86 children, 68 (79.1%) were treated successfully (plasma HIV-1 viral load [VL] <1000 copies/ml), and 63 (73.3%) had full viral suppression (VL <400 copies/ml) after 24 months of ART. No significant difference between successfully treated patients and failure groups was observed in VL, CD4(+) T-cell count or clinical stage at baseline; age at ART start; or ART regimen. All 14 children with VL >5000 copies/ml, one of four children with VL 1000-5000 copies/ml and none with VL <1000 copies/ml developed reverse transcriptase inhibitor (RTI)-resistance mutations by 24 months of ART. Y181C and M184V/I were the most dominant non-nucleoside and nucleoside RTI-resistance mutations, respectively (13/15, 86.7%). These findings suggest that VL testing after 24 months of ART can be used to efficiently differentiate ART failures among HIV-1 vertically-infected children in resource-limited settings.

Objective identification of the caudal border of station 1 for lung cancer surgery.

During lung cancer surgery, a lack of appropriate anatomical landmarks makes the determination of lymph node stations arbitrary. With the aim of remedying this situation, we have focused on the confluence of the internal mammary vein (IMV) to the superior vena cava. Preoperative multidetector computed tomography (MDCT) makes it possible to accurately measure the distance between the caudal border of station 1 and the confluence of the IMV. This preoperative measurement makes the determination of station 1 more objective.

Effect of progesterone on recovery from nerve injury during leg lengthening in rats.

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal. Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis.

Tuberculosis and oral Candida species surveillance in HIV infected individuals in Northern Kenya, and the implications on tuberculin skin test screening for DOPT-P.

OBJECTIVE: To determine the pattern of opportunistic infections such as TB and Candida species in HIV infected patients in Northern Kenya. DESIGN: Cross-sectional study. SETTING: Five health facilities in Moyale (n=224), Mandera (n=121) and Turkana Kakuma; (n=83), Lopiding; (n=94) districts during different periods in 2003. SUBJECTS: Five hundred and fifty two patients. RESULTS: In total 94 (18%) patients were found to be HIV positive (Moyale=42, Mandera=13, Turkana; Kakuma=8, Lopiding=31). Only 65 of 94 HIV positive patients provided saliva samples. Of these, 11 (17%) were TB smear positive and 19 (29.2%) were colonized by oral Candida species. The Candida isolates were as follows; Co-infection of Candida species and TB (n=4), C. albicans only (n=12), C. tropicalis only (n=1), C. albicans and C. glabarata (n=1) and C. albicans, C. glabarata and C. tropicalis. co-infection (n=1). CONCLUSION: The findings provides an important insight into the differences in mucosal susceptibility to bacteria (TB) infection and fungal (Candida species) colonization during HIV immunosuppression, based on collected blood, sputum and saliva specimens. Further studies are needed to elucidate the comparative transmission dynamics and pathogenetic mechanisms of these opportunistic infections-in different regions of Kenya. Such studies would improve the efficiency of directly observed preventive therapy programme (DOPT-P) whose implementation involves screening by tuberculin skin testing.

Rapid alveolar liquid removal by a novel convective mechanism.

Although alveoli clear liquid by active transport, the presence of surface-active material on the alveolar surface suggests that convective mechanisms for rapid liquid removal may exist. To determine such mechanisms, we held the isolated blood-perfused rat lung at a constant alveolar pressure (PA). Under videomicroscopy, we micropunctured a single alveolus to infuse saline or Ringer solution in approximately 10 adjacent alveoli. Infused alveoli were lost from view. However, as the infused liquid cleared, the alveoli reappeared and their diameters could be quantified. Hence the time-dependent determination of alveolar diameter provided a means for quantifying the time to complete liquid removal (C(t)) in single alveoli. All determinations were obtained at an PA of 5 cmH(2)O. C(t), which related inversely to alveolar diameter, averaged 4.5 s in alveoli with the fastest liquid removal. Injections of dye-stained liquid revealed that the liquid flowed from the injected alveoli to adjacent air-filled alveoli. Lung hyperinflations instituted by cycling PA between 5 and 15 cmH(2)O decreased C(t) by 50%. Chelation of intracellular Ca(2+) prolonged C(t) and abolished the inflation-induced enhancement of liquid removal. We conclude that when liquid is injected in a few alveoli, it rapidly flows to adjacent air-filled alveoli. The removal mechanisms are dependent on alveolar size, inflation, and intracellular Ca(2+). We speculate that removal of liquid from the alveolar surface is determined by the curvature and surface-active properties of the air-liquid interface.

[Measles epidemic and investigation of the vaccination history in Chiba Prefecture in 2000. A report from Chiba epidemiological surveillance of tuberculosis and infectious diseases].

A middle-scale epidemic of measles was occurred in Chiba Prefecture, from the beginning of the year in 2000 to September. The Chiba epidemiological surveillance of tuberculosis and infectious diseases committee conducted an investigation of the vaccination history of measles patients, to obtain the prevailing situation of measles and the efficacy of the vaccination. This report summarized results of the epidemiological investigation of measles vaccination history. A total of 1,665 cases were reported during the period. The ratio of the under 1-year-old (who usually do not receive measles vaccine) to all reported cases was 11.4%. The ratio of the vaccinees for the reported cases was 11.8% and this ratio increased in the 5 years old or over. In particular, the 9-year-old age group (26.2%), and 10-14-year-old age group (23.3%) showed a higher ratio than the other age groups. These results indicate that early vaccine inoculation to the under 1-year old group and improvement of the vaccination rate are necessary to prevent measles epidemic. The results also suggest revaccination to higher age groups might be effective.

Natural infection of wild-born mandrills (Mandrillus sphinx) with two different types of simian immunodeficiency virus.

We found a novel primate lentivirus in mandrill (Mandrillus sphinx). To clarify the evolutionary relationships and transmission patterns of human/simian immunodeficiency virus (HIV/SIV), we screened blood samples from 30 wild-born healthy Cameroonian mandrills. Five (16.7%) of them were seropositive for SIV. Three SIV strains were isolated from the five seropositive mandrills by cocultivation of their peripheral blood mononuclear cells (PBMCs) with PBMCs of rhesus macaques, a human T cell line (M8166), and/or a cynomolgus macaque T cell line (HSC-F). One of the newly isolated SIV strains was intravenously inoculated into two rhesus macaques and resulted in chronic infection. In the SIV-infected macaques at 45 weeks after inoculation, we observed a mild decline in the number of peripheral CD4(+) lymphocytes, lymphadenopathy, and blastic follicular dendritic cells with mild follicular hyperplasia in the peripheral lymph nodes. A phylogenetic analysis based on the pol sequence showed that the newly found SIVs from Cameroonian mandrills did not cluster with SIVmndGB1, which is the former representative strain of SIVmnd. The SIVmnds from Cameroon formed a new, independent lineage that branched before the root of the HIV-1/SIVcpz lineage with 996 of 1000 bootstrap replications. They clustered host specifically, and exhibited about 16.9% diversity at the level of nucleotide sequence among Cameroonian SIVmnd strains. These results indicate that the SIVmnds isolated in Cameroon are a novel type of SIVmnd and have infected Cameroonian mandrills for a long time. We therefore designated the Cameroonian SIVmnd as SIVmnd type 2 and redesignated SIVmndGB1 as SIVmnd type 1. To date, M. sphinx is the only primate species other than humans that is naturally infected with two different types of SIV.

Innominate artery rupture after transcervical drainage for descending necrotizing mediastinitis.

We present a case of innominate artery rupture after descending necrotizing mediastinitis (DNM) on day 36 of cervicomediastinal drainage. The patient recovered after aortosubclavian arterial bypass grafting followed by resection of the eroded artery. Because mechanical pressure caused by drains in addition to the inflammatory process can cause major vessel erosion, prolonged transcervical tube drainage for treating descending necrotizing mediastinitis should be avoided even if the drains applied are soft and thin.

Genetic subtypes of HIV type 1 in Republic of Congo.

To assess the molecular epidemiology of HIV-1 in Republic of Congo (Congo), we investigated 29 HIV-1s obtained from 82 Congolese AIDS and ARC patients in 1996 and 1997. Part of the env region including the V3 loop was phylogenetically analyzed. The genotypes observed were varied: of 29 specimens, 12 (41 %) were subtype A, 1 (3%) was subtype D, 6 (21%) were subtype G, 6 (21%) were subtype H, 2 (7%) were subtype J, and 2 (7%) could not be classified as any known subtypes (U, unclassified). The heterogeneous profile of HIV-1 infection was different from the profiles of neighboring Central African countries. These data show that subtypes G and H as well as subtype A were circulating with high prevalence. The fact that new genetic subtypes (J and U) are circulating indicates a need for a greater surveillance for these subtypes both in Congo as well as in other parts of the world.

Cerebral function after aortic surgery using retrograde cerebral perfusion: report of three cases.

INTRODUCTION: The neurological analysis undertaken on three cases of aortic aneurysm treated surgically using retrograde cerebral perfusion (RCP) are reported herein. This is the first detailed analysis of postoperative neurological studies in such cases. METHODS: The oxygenation state of cerebral Hb and cytochrome aa3 levels were monitored by near-infrared spectroscopy (NIR) during RCP. Postoperative neurological scoring, computed tomography (CT), magnetic resonance imaging (MRI), and monitoring of local cerebral blood flow (LCBF) quantatively by N-isopropyl-p-[123I] iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) were performed for an extended follow-up period after surgery. RESULTS: The T2WI of MRI findings which consisted of many spotty high intensity areas in the striatum, cerebellum and hippocampus, may reflect the postoperative severe consciousness and mental disturbances (2-4 weeks). However, in all cases the neurological deficit gradually improved until they returned to their normal preoperative states. The improvement of LCBF correlated well with neurological recovery. CONCLUSION: The conditions of the conventional method of RCP must be improved to prevent transient severe consciousness and mental disturbances which occur after the operation in relationship with the appearance of the high intensity area on the MRI T2WI.

Role of apoptosis induction in both peripheral lymph nodes and thymus in progressive loss of CD4+ cells in SHIV-infected macaques.

To investigate the role of apoptosis in the progressive loss of CD4+ lymphocytes in HIV infection, we have used macaques infected with SHIV, a hybrid virus of HIV and simian immunodeficiency virus (SIV). In the present study, we sequentially analyzed apoptosis induction in the acute phase of SHIV infection. Four macaques infected with a pathogenic SHIV, SHIV89.6P, and four macaques infected with a nonpathogenic SHIV, NM-3rN, were analyzed during the first 2 or 4 weeks postinfection. In the 89.6P-infected macaques the number of peripheral CD4+ cells sharply decreased at 2 weeks postinfection and was maintained below 50/microl until 4 weeks postinfection, while in the NM-3rN-infected macques the number of the CD4+ cells did not change significantly. Plasma viral loads peaked at 2 and 2-3 weeks postinfection, and the peak values were about 1 x 10(9) and 10(6)-10(7) copies/ml in the 89.6P- and the NM-3rN-infected macaques, respectively. In the 89.6P-infected macaques, Fas antigen expression and the extent of apoptosis in PBMCs and peripheral lymph nodes increased at 1-2 weeks postinfection. A high number of apoptotic cells was also observed in thymus sections 2 and 4 weeks postinfection. On the other hand, apoptosis was scarcely induced in the NM-3rN-infected macaques. These results suggest that the extent of apoptosis induction is closely correlated with the pathogenicity of SHIV and that the apoptosis induction in peripheral lymphoid tissues and thymus, where T cell maturation occurs, may play an important role in the depletion of CD4+ lymphocytes in 89.6P infection.

Kinetics of cytokine production in the cornea and trigeminal ganglion of C57BL/6 mice after corneal HSV-1 infection.

To investigate the role of cytokines in the pathogenesis of acute herpetic keratitis (HK), we examined the kinetics of cytokine expression in the corneas and the trigeminal ganglia (TG) of C57BL/6Cr (B6) mice after herpes simplex virus type 1 (HSV-1) infection and observed the influence of the targeted disruption of interferon-gamma (IFN-gamma) gene on the clinical course of HK and/or viral clearance. Following corneal infection with HSV-1 Amakata strain, all corneas developed a typical dendritic keratitis. Quantitative analysis using enzyme-linked immunosorbent assay (ELISA) revealed that the expression of interleukin-1alpha (IL-1alpha), IL-5, IL-6, and IFN-gamma in corneas and TGs significantly elevated immediately after infection, peaked between days 2 and 7 postinfection (p.i.), and then diminished. One exception was IFN-gamma, whose expression significantly persisted in the TGs until day 30 p.i. An additional experiment using IFN-gamma-/- (gko) mice revealed that there was no significant difference in the peak level of viral replication in corneas and TGs between gko and B6 mice, although gko mice showed a significant delay of virus clearance in both corneas and TGs (p < 0.005) and higher mortality rate than B6 mice after HSV-1 infection (p < 0.01). These data suggest that the production of proinflammatory cytokines closely correlates with the pathogenesis of HK, and that IFN-gamma plays an important role in enhancing viral clearance from the cornea and TG.

Cytokine expression and induction of acinar cell apoptosis after pancreatic duct ligation in mice.

To clarify the role of cytokines and acinar cell apoptosis in the pathogenesis of acute pancreatitis, we investigated the expression of intrapancreatic cytokines and apoptosis-related molecules in mice after pancreatic duct ligation (PDL). From day 1 or 3 after PDL, the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor (TNF-alpha) mRNA were up-regulated in the pancreas, suggesting that these cytokines may be involved in the development of pancreatitis after PDL. Acinar cell apoptosis was observed in the pancreas at rates of 0.13 +/- 0.03, 1.32 +/- 0.38, and 0.86 +/- 0.23% on days 1, 3, and 7 after PDL, respectively. Significant increases in intrapancreatic mRNA levels of TNF-alpha, Fas ligand (FasL), and IL-1beta-converting enzyme (ICE) were observed from day 3 after PDL with the appearance of acinar cell apoptosis. The serum amylase activity peaked on day 1 after PDL and gradually decreased on days 3 and 7 after PDL. These results suggest that acinar cell apoptosis induced after PDL may modulate the progression of acute pancreatitis by reducing the release of digestive enzymes and may therefore be a host defense mechanism, and that acinar cell apoptosis after PDL may be mediated by the TNF-alpha and/or Fas/FasL and ICE system.

[Anti-emetic treatment for patients with non-small cell lung cancer after chemotherapy, usefulness of preventive combination of anti-emetic agents and importance of psychiatric aspect of patients].

Preventive combined administration of granisetron 3 mg, methylprednisolone 500 mg, and metoclopramide 40 mg decreased the post-chemotherapy emesis from 56% in 68 control cases to 16% in 31 administered cases. All cases had non-small cell lung cancer and were treated with cisplatin 80 mg/m2, vindesine 3 mg/m2, and mitomycin C 8 mg/m2. YG character test in 23 cases revealed that emotional unstableness, characterized by the coupled rightward shift of the N (nervous) and I (inferior complex) components, was the important cause of emesis in those patients who failed to respond to the anti-emetic drugs shown above. Anti-emetic agents with different mechanisms and psychiatric counseling are needed in these emotionally unstable patients.

Differentiation of a cell line of human cervical argyrophil small cell carcinoma to macrophage lineage cells.

To investigate the origin of argyrophil small cell carcinoma (ASCC) of the uterine cervix, we examined the influence of dibutyryl cyclic adenosine 3',5'-monophosphate (dB-cAMP), a known differentiation inducer, on the characteristics of an ASCC cell line, TC-YIK, which has been shown to be a useful in vitro experimental model of ASCC. In TC-YIK cells after treatment with dB-cAMP, two specific antigenic markers of macrophages, CD14 and human leukocyte antigen-DR, were detected by flow cytometric analysis. In addition, interferon-gamma mRNA was detected by reverse transcription-polymerase chain reaction and interferon-gamma protein was detected by ELISA. More than 90% of the cells stained positive for alpha-naphthyl butyrate esterase, 1% of the cells showed phagocytotic activity against Micrococcus lysodeikticus, and 22% of the cells had M. lysodeikticus adsorbed on their surface. Furthermore, granulocyte-macrophage colony stimulating factor accelerated the proliferation of TC-YIK cells. These results indicate that dB-cAMP promotes differentiation of ASCC cells to macrophages. In contrast, less than 10% of the cells showed stellate morphology, suggesting differentiation to neuronal cells after treatment with dB-cAMP, as reported previously. Thus, TC-YIK cells have been shown to differentiate both into macrophage lineage cells and neuronal cells, suggesting that ASCC originates from undifferentiated stem cells.

Sequential analysis of apoptosis induction in peripheral blood mononuclear cells and lymph nodes in the early phase of pathogenic and nonpathogenic SIVmac infection.

To investigate the role of apoptosis in the early phase of HIV infection, we used macaques infected with simian immunodeficiency virus strain mac (SIVmac) as a primate model and examined sequentially the characteristics of apoptosis of lymphocytes in peripheral blood mononuclear cells (PBMCs) and lymph nodes in the early phase of SIVmac infection. Five macaques infected with a pathogenic strain of SIV, SIVmac239, were analyzed during the first 4 weeks after infection. Peripheral CD4+ and CD8+ cells transiently decreased at 1 week postinfection. The percentage of apoptotic cells in cultured PBMCs increased from about 2 weeks postinfection. The number of apoptotic cells in lymph node sections was higher on days 13 and 28 postinfection than before infection and on day 5 postinfection. Fas antigen expression on peripheral lymphocytes was upregulated from day 8 postinfection. These results indicate that apoptosis is induced about 2 weeks after SIVmac239 infection, following the upregulation of Fas antigen expression on lymphocytes. Since apoptosis was induced about 1 week after the decrease in peripheral CD4+ and CD8+ cell counts, it appears that the apoptosis induction does not play an important role in the transient lymphopenia in the early phase of SIVmac infection. In macaques infected with a nonpathogenic derivative of SIVmac239, SIVmac delta nef, apoptosis of lymphocytes was induced as it was in SIVmac239-infected macaques, but to a lesser degree, suggesting a correlation between the extent of apoptosis induction in lymphocytes in the early phase of SIVmac infection and the pathogenicity of SIVmac.

Isolation and characterization of rice MADS box gene homologues and their RFLP mapping.

Thirty-five MADS box gene homologues were identified through a large-scale cDNA analysis in rice. Based on the nucleotide sequences of the 3'-untranslated region, these clones were classified into 11 independent species. Seven species were found to be new among the rice MADS box gene family, and the other 4 corresponded to the previously reported OsMADS1, OsMADS2, OsMADS4, and OsMADS5. The full nucleotide sequences of the 7 new species were determined. Each clone encoded a deduced protein of 164-267 amino acids. The K-domain of the MADS protein was conserved in all clones though with lower degree in clone S10304. Reverse transcription PCR analysis showed that clones E31254 and E31864 were expressed mainly in panicles. Dendrogram analysis suggested that E31254 and E31864 are close to Arabidopsis AGL9 and AP1, respectively. Restriction fragment length polymorphism (RFLP) linkage mapping revealed that the rice MADS box gene homologues reported here are not clustered but are located throughout the genome. The locus of E31864 on the RFLP map was closely linked to the long sterile lemma gene, g-1.

Interleukin-9 receptor alpha chain mRNA formation in CD8+ T cells producing anti-human immunodeficiency virus type 1 substance(s).

A search for gene(s) associated with anti-human immunodeficiency virus type 1 (HIV-1) activity of CD8+ T cells was attempted using molecular cloning and the relation between the anti-HIV activity of CD8+ T cells and the interleukin-9 receptor alpha chain (IL-9R-alpha) mRNA expression from the cDNA clones obtained was examined. The anti-HIV-1 activity of CD8+ T cell culture supernatants was assessed by measuring the level of HIV-1 replication of a CD4+ T cell line transfected with an infectious HIV-1 DNA clone. IL-9R-alpha mRNA was assayed by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 5 cases showing high level of anti-HIV-1 activity (more than 80% suppression of HIV-1 replication), the mRNA was detected in 4 cases. Of 10 cases showing low level of anti-HIV-1 activity (less than 80% suppression of HIV-1 replication), the mRNA was detected in one case. Soluble recombinant human IL-9 receptor (rhIL-9sR) did not suppress HIV-1 replication at a concentration of 1 microgram/ml. These data suggest that the IL-9R-alpha mRNA formation in CD8+ T cells may correlate with and play some role in the anti-HIV-1 activity of CD8+ T cells from HIV-1-infected individuals.