Effect of influenza virus vaccine on the expression of human immunodeficiency virus co-receptor CCR5.

BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are known to play an important role in HIV cell entry and viral replication. OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors and on viral load in HIV-infected children. METHODS: Eight HIV-infected children receiving stable therapy and 11 healthy adults were enrolled. Chemokine expression and immune activation were determined before and 48 hours after influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed using real-time polymerase chain reaction. Viral load was measured at baseline, 48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1% vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P = .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in controls; P = .02) lymphocytes. This was observed in conjunction with an increase in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte counts, expression of interleukin 2 receptor and CXCR4, or gene expression of CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T lymphocytes. However, this immunomodulatory effect does not seem to affect overall viral replication in HIV-infected children who received highly active antiretroviral therapy.     

Heat-shock induced nuclear retention and recycling inhibition of importin alpha

Heat-shock induces a strong stress response and modifies all aspects of cellular physiology, which involves dynamic changes in the nucleocytoplasmic distributions of a variety of proteins. Many distinct nucleocytoplasmic transport pathways exist in eukaryotic cells, but how a particular transport pathway is regulated under different cellular conditions remains elusive. The finding of this study indicate that conventional nuclear import, which is mediated by importin alpha/beta, is down-regulated, while the nuclear import of 70 kD heat-shock cognate protein is up-regulated in heat-shock cells. Among the factors involved in the mediation of the conventional nuclear import, significant levels of importin alpha accumulate in the nucleus in response to heat-shock. An analysis of the behaviour of importin alpha with fluorescence recovery after photobleaching and fluorescence loss in photobleaching studies show that nuclear importin alpha becomes less mobile and its nucleocytoplasmic recycling is impaired in heat-shock cells. These data coincided well with biochemical and cytological studies. Our present data show that heat-shock induces the nuclear accumulation, nuclear retention, and recycling inhibition of importin alpha, resulting in the suppression of conventional nuclear import. This suggests a new regulatory mechanism for the adaptation of cells to environmental changes, such as heat-shock.     

The effect of sustained-release theophylline granules in the inhibition of exercise-induced asthma]

We studied the protective effect of sustained-release theophylline granules on early or late response in exercise-induced asthma (EIA) in 16 patients ranging in age from 7 to 18 years. A standardized exercise test was examined 2 hours after administration of theophylline granules on one day and after no medication on another day. On both days, the lung functions and the serum theophylline and cortisol concentrations of the patients were examined before exercise and over a period of 8 hours after exercise. On days without medication, early response was seen in 16 patients and late response in 6. On days with medication, the theophylline granules inhibited early response in 13 of the 16 patients and late response in 5 of the 6 patients. This suggests that theophylline preparation is a useful drug for inhibiting the dual responses of EIA.     

Idiopathic right ventricular dilation. Special reference to "arrhythmogenic right ventricular dysplasia" and analogous lesions

Two autopsy cases which showed marked depletion of the right ventricular musculature of the heart accompanied with marked infiltration of the adipose tissue were reported. The first cases was an 18-year-old female who died of right sided congestive heart failure after about 4-years clinical course. The autopsy disclosed marked dilation of the right atrium and ventricle. The entire free wall of the right ventricle was markedly thin. Microscopically, most of the myocardial fibers of the right ventricle were replaced by fat and fibrous tissue. The second case, a 15-year-old boy, whose identical twin was previously diagnosed as arrhythmogenic right ventricular dysplasia designated by Fontaine et al., died suddenly during exercise. He showed no cardiac symptoms but electrocardiogram was abnormal. Autopsy revealed majority of the myocardial fibers of the right ventricular free wall were replaced by fatty tissue. In both cases, fatty infiltration was mainly noticed at the epicardial side and some myocardial fibers remained in the fatty tissue showed hypertrophic and/or degenerative changes. Review of the literature on similar cases showing depletion of the right ventricular musculature including so-called adult's Uhl anomaly, ARVD and dilated right ventricular myocardiopathy was conducted and the relationship of the present cases with these lesions was discussed.     

Spectral imaging fluorescence microscopy

The spectral resolution of fluorescence microscope images in living cells is achieved by using a confocal laser scanning microscope equipped with grating optics. This capability of temporal and spectral resolution is especially useful for detecting spectral changes of a fluorescent dye; for example, those associated with fluorescence resonance energy transfer (FRET). Using the spectral imaging fluorescence microscope system, it is also possible to resolve emitted signals from fluorescent dyes that have spectra largely overlapping with each other, such as fluorescein isothiocyanate (FITC) and green fluorescent protein (GFP).     

Craniopharyngioma presenting a symptom of pituitary apoplexy and hyponatremia: a case report

We report a case of a 70-year-old woman admitted to our hospital with sudden headache, drowsiness and hyponatremia. MRI on admission showed an intrasellar mass with suprasellar extension. Serum examination revealed decreased sodium and hypopituitarism, but they were normalized gradually by compensation using hydrocortisone, thyroid hormone and salt. Afterwards, masked diabetes insipidus appeared and required aqueous pitressin for the control of urine volume. A removal operation was performed uneventfully using the transsphenoidal approach and histological examination confirmed squamous-papillary type craniopharyngioma. Intratumoral hemorrhage of the craniopharyngioma is extremely rare. These cases tend to occur after over 15 years of maturation and the squamous-papillary type tend to bleed more than the adamantinomatous type. However, it is very difficult to make a differential diagnosis between craniopharyngioma with intratumoral hemorrhage and pituitary apoplexy, judging only by symptoms or interventional radiology. The definite mechanism of hyponatremia associated with a parasellar lesion is still obscure, but compression to the anterior hypothalamus or pituitary gland by an enlargement of the parasellar tumor is generally hypothesized.     

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor

We report a case of adenosquamous carcinoma of the stomach that produced granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of infection. After leukemia and metastatic leukemoid reaction were excluded by bone marrow examination, a G-CSF-producing cancer was suspected as the cause of the abnormally elevated serum G-CSF level. The resected stomach tumor was histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF by tumor cells was shown with immunohistochemical detection, which confirmed the preoperative diagnosis. Recurrent disease in the liver and lymph nodes, accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3 months after the curative gastrectomy and adjuvant chemotherapy. All of the recurrent disease was resected, restoring normal levels of serum G-CSF. The patient survived for almost 2 years after the initial surgery with extensive chemotherapy, including weekly treatment with paclitaxel, before finally succumbing to liver failure secondary to extensive liver metastasis.     

Valpha24+ natural killer T-cell responses against T-acute lymphoblastic leukaemia cells: implications for immunotherapy

Human Valpha24+ natural killer T (NKT) cells correspond to mouse Valpha14+ NKT cells, both cell types use an invariant T-cell receptor-alpha chain and are activated by glycolipids in a CD1d-dependent manner. Mouse Valpha14+ NKT cells have been reported to have an antitumour effect in vivo. Human Valpha24+ NKT cells can kill a proportion of tumour cells in a CD1d-dependent manner in vitro. We report here that many human leukaemic T-cell lines express CD1d and can be directly killed by Valpha24+ NKT cells. This killing activity was enhanced in the presence of alpha-galactosylceramide (alpha-GalCer), a ligand of Valpha24+ NKT cells. Moreover, primary leukaemic T cells from five of eight T-cell acute lymphoblastic leukaemia (T-ALL) patients expressed CD1d and were good targets of Valpha24+ NKT cells. This cytotoxicity was increased in the presence of alpha-GalCer. Our results suggest that T-ALL is a good candidate for Valpha24+ NKT-cell-based immuno-cell therapy.