The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial

OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. CONCLUSION: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.     

Effects of hot deep seawater bathing on the immune cell distribution in peripheral blood from healthy young men

Objectives Deep seawater (DSW) utilization technology has been developed for the fields of medicine and health, among others. To clarify the health effects of DSW as compared with surface seawater (SSW) or tap water (TW), we investigated the changes of immune cell distribution of the peripheral blood, or subjective judgment scores, after hot water bathing. Methods Ten healthy young men were immersed for 10 min in DSW, SSW and TW heated to 42°C. Blood samples were collected before bathing, immediately after bathing and 60 min after bathing. Total and differential numbers of leucocytes and lymphocyte subsets (CD3, CD4, CD8, CD19, CD16, and CD56) were examined using an automated hematology analyzer and a flow cytometer, respectively. The subjective judgment scores were obtained by an oral comprehension test. Results Since the pre-bathing leukocyte count in the TW group was significantly different from those in the DSW and SSW groups, we excluded the findings of TW bathing from consideration. In hot DSW bathing, CD8-lymphocytes increased significantly immediately after bathing (p<0.05), in contrast to hot SSW bathing, in which no significant changes were detected in the lymphocyte subsets. Additionally, there were no significant changes between repeated measurements in the subjective judgment scores, though the score of thermal sensation in SSW bathing showed a significantly higher value immediately after bathing than before bathing (p<0.01). Conclusions Our findings suggest that increased CD8-lymphocytes in hot DSW bathing may improve human immune function as well as hot springs do, as compared with SSW bathing. Although hot DSW bathing may have the ability to change human immune cell distribution, well-designed studies are needed to clarify the health effects including not only DSW and SSW but also TW.     

Screening of selected basidiomycetes for inhibitory activity on Clostridium histolyticum collagenase and human leukocyte elastase

Collagenase and elastase play a critical role in the degradation of connective tissue. Aqueous and dichloromethane extracts of 15 Basidiomycetes were screened for their ability to inhibit the activity of collagenase and elastase. Collagenase (EC 3.4.24.3) was not inhibited by aqueous extracts, but by dichloromethane extracts in concentrations of 200 microg/mL. For seven extracts an IC(50) less than 200 microg/mL could be observed. Elastase (3.4.21.37) was inhibited by both aqueous and dichloromethane extracts of the Basidiomycetes, with the aqueous extracts active at concentrations of 200 microg/mL. Five extracts inhibited strongly, with an IC(50) 2-20 microg/mL. Except for four, all dichloromethane extracts inhibited the enzyme in concentrations of 2 microg/mL, nine of them very strongly at about 90%.     

Systemic lupus erythematosus of childhood onset: correlation between T cells expressing early and late activation antigens and disease activity

Correlation between T cell phenotypes, especially activated T cells expressing early (EA1) and late (HLA-DR) activation antigens and clinical features were investigated in 22 patients with systemic lupus erythematosus (SLE) of childhood onset. Percentages of T cells expressing EA1 and HLA-DR in 22 patients with SLE were significantly higher than those in controls. Comparison of T cell phenotypes between patients with active and inactive SLE showed that eight patients with active disease had significantly increased percentages of HLA-DR positive T cells than 14 with inactive disease (P<0.01). Serial examinations showed that the percentages of HLA-DR positive T cells were decreased after therapy in seven with active non-renal or active non-renal and renal diseases but not in one with only active renal disease. A possible significance of T cells expressing EA1 and HLA-DR in the management of patients with SLE is discussed.Abbreviations HLA-DR human leukocyte antigens-DR - SLE systemic lupus erythematosus     

Binding of human secretory leukocyte protease inhibitor in uterine cervical mucus to immunoglobulins: pathophysiology in immunologic infertility and local immune defense

Objective: To identify an Fc receptor–like molecule in human cervical mucus.

Design: Controlled experimental laboratory study.

Setting: Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima.

Patient(s): Women undergoing treatment for infertility.

Intervention(s): Sodium dodecyl sulfate-polyacrylimide gel electrophoresis and Western blot were used for analysis.

Main Outcome Measure(s): A water-insoluble protein with immunoglobulin-binding activity was purified from human cervical mucus by ammonium sulfate fractionation. The initial 21 amino acids of the N-terminus of the immunoglobulin-binding protein were determined and analyzed in a computer search for homology.

Result(s): The purified fraction contained a 15-kd protein that binds immunoglobulin A, immunoglobulin M, and all subclasses of human immunoglobulin G as determined by Western blot analysis. The amino acid sequence of the N-terminus is identical to that of secretory leukocyte protease inhibitor. The capacity of secretory leukocyte protease inhibitor to bind immunoglobulins was confirmed by Western blot analysis.

Conclusion(s): A component in human cervical mucus capable of binding immunoglobulins was identified as secretory leukocyte protease inhibitor. The capacity to bind immunoglobulins is a unique property of the protein, providing additional support for the contention that it plays an important physiologic role in local tissue defense mechanisms. It also is involved in the pathogenesis of immunologic infertility by trapping sperm in the cervical mucus.     

动脉硬化性脑梗死与HLA—I类基因的关联性研究

目的 探讨动脉硬化性脑梗死（ABI）与人类白细胞抗原（HLA）系统的相关性,方法 采用微量淋巴细胞毒分型方法,对我国北方汉族人群39例ABI患者和41例健康对照组的HLA－A,B,C各等位基因共计66个位点进行检测分析。结果 ABI组HLA－A30基因频率较对照组显著增加（RR＝10．36,P＜0．01）,其他HLA－A,B,C基因频率未见与ABI明显相关,结论 HLA－A30基因可能为AB1的易感基因,其可能与ABI致病基因有连锁不平衡或作为免疫应答基因而导致ABI发生,HLA－A30基因可视为ABI高危险性遗传标志。     

Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon

Summary Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-A) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-A following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-A following intravenous and intramuscular administration of 3, 9 or 18×10⁶ units to patients with disseminated cancer.A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1).     

The effect of propranolol on exercise induced tachycardia is determined by plasma concentration and the density of adrenergic receptors on leukocytes

Summary The chronotropic response to a single oral dose of propranolol in 23 healthy subjects has been related to the plasma propranolol concentration and the density of -adrenoceptors on peripheral polymorphonuclear leucocytes. The percentage reduction in exercise-induced tachycardia was significantly correlated with the log plasma propranolol concentration within subjects but not between subjects. Taking the concentration of the active metabolite 4-hydroxypropranolol into account did not improve the interindividual correlation. The reduction in exercise-induced tachycardia was significantly correlated with the maximum binding density of (¹²⁵I)-hydroxybenzylpindolol on polymorphonuclear leucocyte membrane fragments measured before medication. A response index (% reduction in exercise-induced tachycardia/plasma propranolol concentration) was correlated with the maximum binding density of (¹²⁵I)-hydroxybenzylpindolol (predrug) at 2 h (r_s=0.72), 4 h (r_s=0.84) and 6 h (r_s=0.73) after dosing. The data suggest that interindividual variation in the response to propranolol after a single oral dose is determined by interindividual differences both in plasma propranolol and adrenoceptor density.     

Transfusion related acute lung injury: a pediatric perspective

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. TRALI occurs in children and adults, but the syndrome has not been reviewed from a pediatric perspective. We reviewed the literature on TRALI from a pediatric perspective. TRALI has been documented in pediatric patients, especially in the setting of hematologic malignancy. Additional TRALI cases have been reported in pediatric patients with a variety of diagnoses. TRALI is likely to be much more common than previously appreciated in the pediatric patient population. TRALI should be considered in the differential diagnosis of all pediatric patients who develop new acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) during or within six hours of a blood product transfusion. When a case of TRALI is suspected, a transfusion reaction report to the blood bank is important to initiate the investigation and identify the implicated donor.     

Protective effect of polyethylene glycol-superoxide dismutase on leukocyte dynamics in rat retinal microcirculation under lipid hydroperoxide-induced oxidative stress

The levels of lipid hydroperoxide (LHPs) in vitreous are elevated in a variety of retinal disorders. Recently, we have shown that increased levels of LHPs in the vitreous enhanced leukocyte-endothelium interaction in the retina, which should contribute to the initial disturbance of the retinal microcirculation. Based upon the previous work, the purpose of the present study was to investigate the effect of polyethylene glycol-superoxide dismutase (PEG-SOD), one of the important enzyme antioxidants, on leukocyte-endothelial interaction in the retinal microcirculation under LHP-induced oxidative stress. Male Brown-Norway rats weighing approximately 250 g were used. LHP(18:2) was made from linoleic acid (LA) with lipoxygenase and 10 microg of LHP dissolved in 5 microl of sodium borate buffer (SBB, 0.02 m) was slowly injected into the vitreous using a 33-gauge needle. PEG-SOD (5000 units/kg) was given intravenously 5 min before LHP injection. At 2, 4, 6, 12, 24 and 48 hr after the vitreous injections, we evaluated the number of rolling leukocytes along the major retinal veins and the number of leukocytes that accumulated in the retinal microvasculature with acridine orange digital fluorography. In LHP-treated rats, leukocyte rolling along the major retinal veins was maximal at 6 hr after LHP injection. The number of rolling leukocytes in the PEG-SOD-treated rats was decreased to 5.5% of those in the LHP-treated rats at 6 hr after LHP injection (P<0.01). No rolling leukocytes were observed in either control or vehicle-treated eyes. The number of accumulated leukocytes in LHP-treated eyes started to increase at 12 hr, and peaked at 24 hr which was significantly higher than in both control and vehicle-treated eyes (P<0.01). The number of accumulated leukocytes in the PEG-SOD-treated rats was reduced by 88.0% at 24 hr (P<0.01). Intravenous injection of PEG-SOD significantly inhibited the leukocyte rolling and its accumulation under LHP-induced oxidative stress. These results suggest that PEG-SOD might attenuate various retinal microcirculatory disorders associated with LHP.