Analysis of recombinant human tumour necrosis factor-alpha-induced CD4 expression on human eosinophils.

We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-alpha (rhTNF-alpha) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-alpha induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-alpha-induced CD4 expression was significantly inhibited by 10(-6) M cycloheximide, 10(-8) M dexamethasone, or 10(-6) M herbimycin A. Recombinant human interferon-gamma inhibited rhTNF-alpha-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-alpha-induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity.     

Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.     

松果体区病灶直线加速器放射外科的剂量分布探讨

通过运用仿真人体模型对松果体区靶病灶直线加速器多聚弧照射的监测，论证直线加速器作为放射外科工具治疗颅内病变的科学性，探讨有关辐射参数对剂量分布的影响。作者认为，直线器放射外科可实现与伽玛马相似的剂量分布，同是神经外科安全有效的治疗技术，准直器孔径越小，照射范围越大，则剂量梯度即越大，剂量分布越理想；靶区最大剂量对上器孔径有相当高的依赖性，本文还就合理的照射弧范围及边缘处方剂量作了讨论。     

Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target

This study demonstrates that the flavonoid quercetin (Q), a plant-derived compound with low toxicity in vivo, greatly potentiates the growth-inhibitory activity of Adriamycin (ADR) on MCF-7 ADR-resistant human breast cancer cells. The effect of Q was dose-dependent at concentrations ranging between 1 and 10 M. Since ADR resistance in these cells is associated with the expression of high levels of P-glycoprotein (Pgp), we evaluated the effect of Q and related flavonoids of Pgp activity in cytofluorographic efflux experiments with the fluorescent dye rhodamine 123 (Rh 123). Our results indicate that Q and 3-OMe Q (3,4,7-trimethoxyquercetin) but not the 3-rhamnosylglucoside of Q (rutin) inhibit the Pgp pump-efflux activity in a dose-related manner. Moreover, 10 M Q reduces the expression of the immunoreactive Pgp in MCF-7 ADR-resistant cells as evaluated by cytofluorimetric assay. In conclusion, these findings provide a further biological basis for the potential therapeutic application of Q as an anticancer drug either alone or in combination with ADR in multidrug-resistant breast tumor cells.This work was partially supported by grants from MURST (60% and 40%) and CNR (Special Projects: A.C.R.O. 94.01098.PF 39); R. DeVincenzo and G. Ferrandina are recipients of fellowships from the Italian Association for Cancer Research (AIRC); M. Cianfriglia was partly supported by the AIDS research project (contract 720/P)     

Paroxysmal dystonia and paroxysmal tremor in a young patient with multiple sclerosis

A 16-year-old patient with multiple sclerosis (MS) showed paroxysmal movement disorders during a recurrence of the disease. The paroxysms took the form ot brief unilateral dystonic posturings of the right body suggestive of paroxysmal dystonia (PD); they completely receded with acetazolamide. A single episode of a high amplitude, rythmic slow and coarse generalized tremor, present at rest and increasing with movement, particularly involving the head in a no-no movement, occurred soon after recovery from PD and lasted three hours. The present report provides evidence that MS has to be considered in the diagnostic approach to symptomatic childhood PD and underlines the efficacy of acetazolamide in the treatment of PD attacks. It also describes a rare paroxysmal movement disorder, defined as paroxysmal dystonic tremor, that can be considered as falling within the spectrum of PD.This study was partially supported by the Paolo Zorzi Association for Neurosciences, and the Harry De Jur Foundation.     

Changes of hepatic vitronectin levels in patients with chronic hepatitis C treated with interferon alpha

Hepatic vitronectin expression was assessed in 27 patients with chronic hepatitis C before and after interferon alpha treatment and in 7 control patients. Before interferon therapy, vitronectin was localized in the hepatocytes and in the portal and central venous regions. A high correlation was found for the vitronectin expression level with the histological grading and staging scores in the hepatocytes as well as in the portal region. After interferon therapy, the hepatic vitronectin was significantly decreased in the sustained and transient responders, but it was not as markedly decreased in the nonresponders and the non-treated group. A good correlation was found for the vitronectin expression with the staging scores but not with the grading scores in the portal region. These findings suggest that hepatic vitronectin is influenced by interferon therapy and that it may play an important role as a hepatic adhesion molecule through the improvement of inflammation, necrosis and fibrogenesis.     

Nasal continuous positive airway pressure changes blood pressure "non-dippers" to "dippers" in patients with obstructive sleep apnea

To evaluate the circadian pattern of blood pressure (BP) and the effects of nasal continuous positive airway pressure (CPAP) on patients with obstructive sleep apnea (OSA), we examined 24-hour BP in 38 male OSA patients with and without nasal CPAP. We measured the BP at 30-min intervals during daytime (800 to 2200) and nighttime (2200 to 800) hours. A "dipper" was defined as a patient who showed an average reduction of at least 10 mm Hg systolic and 5 mm Hg diastolic between daytime and nighttime values. The subjects were predominantly "non-dipper" (22 of 38 patients, 58%). Daytime hypertension (>160/95 mm Hg) was present in 11 of 38 patients (4 "dippers" and 7 "non-dippers"). After nasal CPAP treatment for 3 days, the average BP decreased significantly during the day and night in all subjects (p<0.05). Fifteen of 22 subjects who were "non-dippers" before treatment reversed to become "dippers." And daytime hypertension was detected in only 5 of these patients during nasal CPAP treatment (4 "dippers" and 1 "non-dipper"). These results showed that the "non-dipper" status was common in patients with OSA, and that nasal CPAP restored the normal circadian "dipper" pattern. We suggest that nasal CPAP may contribute to an improved prognosis in patients with OSA because of a reduction in cardiovascular risk factors in "non-dipper" with severe OSA.     

Urinary incontinence after non-nerve-sparing radical prostatectomy with neoadjuvant androgen deprivation

OBJECTIVES: The impact of non-nerve-sparing retropubic radical prostatectomy (RRP) for prostate cancer combined with neoadjuvant androgen deprivation on urinary control is not well documented. We examined the incidence and severity of urinary incontinence after such therapy and determined the etiologic factors causing this complication. METHODS: We examined the postoperative continence status of 104 consecutive patients admitted to the National Cancer Center Hospital who underwent RRP with wide resection of the pelvic nerves after neoadjuvant androgen deprivation. Incontinence was scored according to the number of pads used daily by the patient for urinary leakage. The severity of incontinence was analyzed according to patient age, weight of resected specimen, status of cancer stage, duration of neoadjuvant androgen blockade therapy, preoperative length of membranous urethra, and duration of urethral catheterization after surgery. We also measured the configuration and diameter of the reconstructed bladder neck by retrograde cystourethrography. RESULTS: In 104 patients examined, the percentage of patients who became dry postoperatively was 22% at 1 month, 47% at 3 months, 69% at 6 months, and 78% at 1 year. Of 81 patients who became dry postoperatively at any interval, 22 (27%) became continent within 1 month of RRP, 49 (61 %) were continent within 3 months, 71 (88%) became continent by 6 months, and another 10 (12%) became continent between 6 and 12 months postoperatively. Of 48 patients who were followed up for more than 1 year and for whom continence status at 1 month after surgery was available, all patients who used 1 to 2 pads per day (13 of 13) at 1 month after surgery regained continence by 1 year after surgery. However, only 62% of patients (16 of 26) who required more than 3 pads per day at 1 month after surgery became dry by 1 year after surgery. Only age (older than 70 years) and large prostate size (weight of surgical specimen more than 40 g) temporarily influenced the recovery of urinary continence after surgery. Dilation of the bladder neck evaluated by retrograde cystourethrography was prominent in severely incontinent patients in the immediate postoperative period. CONCLUSIONS: Our experience in patients who undergo non-nerve-sparing RRP after neoadjuvant androgen deprivation closely matches published surveys of patient-reported complications. Postoperative incontinence is not a major contraindication for non-nerve-sparing RRP after neoadjuvant endocrine therapy. Dilation of the bladder neck affected the recovery from incontinence, highlighting the importance of adequate reconstruction of the bladder neck.     

Prediction of viability of ischemically damaged canine pancreatic grafts by tissue flow rate with machine perfusion.

We studied the viability of canine pancreatic grafts using a short-time perfusion technique with an organ perfusion machine, "ORPH3000C". The following parameters were examined during perfusion of warm ischemically damaged grafts: Amylase, lipase, and insulin levels in the perfusate after 1-hr perfusion showed no significant correlation with warm ischemic time (WIT), and these indices could not be used to assess graft viability. Tissue flow rate (TFR) at the end of perfusion was significantly decreased with prolonged WIT. TFR correlated with the percent decrease in tissue SOD activity, thus TFR was a reliable predictor of reperfusion injury. Histological studies showed no findings attributable to warm ischemic injury before 1-hr perfusion. After 1-hr perfusion, the grafts were allotransplanted and the relation between TFR and endocrine function of the transplanted grafts was examined. TFR correlated with K value calculated from IV-GTT performed on day 5 postoperatively, suggesting that TFR is a predictable index of isolated pancreatic graft viability. Using TFR levels, this method allowed us to select only grafts with good function prior to transplantation. This technique appears to be of use for pancreatic transplantation from cadaver donors after cardiac arrest.