EAACI Position paper on the standardization of nasal allergen challenges.

Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.

Distal radius fixation through a mini-invasive approach of 15 mm. Part 1: feasibility study.

The aim of this study was to determine the feasibility of a mini-approach for distal radius volar plating. A 15-mm incision was made in 11 cadaver wrists. A 41 mm length and 24 mm width plate was placed deep to the pronator quadratus then fixed using 2 K-wires. The 2 central epiphyseal screws were placed before pin removal, the lateral screws followed and finally the proximal ones. The number of control views needed was on average 1.9 mm, and the position of the plate was good in 10 cases and average in 1 case. The size of the incision after the operation was on average 16.3 mm. No complications were found. Our results show that volar plate fixation of distal radius fracture is feasible through a 15 mm approach. This approach is esthetic, respects noble structures and facilitates reduction due to ligamentotaxis.

Nicotinamide mononucleotide inhibits oxidative stress-induced damage in a SIRT1/NQO-1-dependent manner.

Oxidative stress causes endothelial dysfunction, which is associated with vascular cellular aging and is causally related to cardiovascular disease pathogenesis. Preclinical studies indicate that a nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide mononucleotide (NMN), alleviates oxidative stress in aged vessels, granting vasoprotective effects. However, the associated cellular mechanism remains largely unclear. In this study, we used human umbilical vein endothelial cells (HUVECs) to demonstrate that NMN inhibits oxidative stress-induced damage by activating the sirtuin 1 (SIRT1)/NAD(P)H: quinone oxidoreductase 1 (NQO-1) axis. We found that NMN inhibited H2O2-induced cytotoxicity and senescence-associated protein expression, such as p16 and p21. Furthermore, NMN prevented H2O2-induced actin cytoskeletal disorganization via inhibiting reactive oxygen species (ROS) production. NMN increased NQO-1 mRNA and protein expression that in turn was abrogated by SIRT1 inhibition, suggesting that NMN-inducible NQO-1 was associated with SIRT1 activity. SIRT1 and NQO-1 inhibition attenuated the inhibitory effect of NMN on H2O2-inducible cytotoxicity, senescence-related protein upregulation, and actin cytoskeletal disorganization. Our findings provide new insights into the mechanism by which NMN exerts protective effects against vascular oxidative stress.

Development of a pattern to measure multiscale deformation and strain distribution via in situ FE-SEM observations.

We investigated a method for measuring deformation and strain distribution in a multiscale range from nanometers to millimeters via in situ FE-SEM observations. A multiscale pattern composed of a grid as well as random and nanocluster patterns was developed to measure the localized deformation at the specimen surface. Our in situ observations of a carbon fiber-reinforced polymer matrix composite with a hierarchical microstructure subjected to loading were conducted to identify local deformation behaviors at various boundaries. We measured and analyzed the multiscale deformation and strain localizations during various stages of loading.

[A trick to improve the technique of the IntraVascular Stent (IVaS): "Clip Stent"]. / Une astuce pour améliorer la technique du stent intravasculaire (IVaS) : le "Clip Stent".

The infra-millimetre vessels are difficult to suture, because the placement of forceps in the lumen is delicate and threads often cross the walls. The technique of the IntraVascular Stent (IVaS), developed to remedy it, did not make the proof of its superiority. The purpose of this study was to analyze the results of a variant, the Clip Stent. Our series included two groups of 10 rats. In group I, the artery of the tail was anastomosed by threads of nylon 10/0. In group II, the artery was anastomosed according to the technique of Clip Stent including three stages: introduction of a monothread of polypropylene 6/0, anastomosis by threads of nylon 10/0, ablation of the Clip Stent and the closure of possible leaks. The assessment consisted in measuring the time of anastomosis, in counting the number of separate threads and leaks, and in testing the permeability. The time of anastomosis was longer 12 minutes in the group II. The number of points by anastomosis was 6.5 in the group I and of 5.5 in the group II. The permeability was 90% in two groups. The Clip Stent is faster than the IVaS. It is useless to realize vascular threads of the lumen before the introduction of the stent. Once the stent in position, it cannot traumatize the intima and its migration is impossible. Contrary to the IVaS, the Clip Stent allows to realize the last threads stent in position, by releasing the tourniquet. The ablation is safe. Its superiority to the conventional methods remains to demonstrate by improving its introduction in the lumen.

Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma.

BACKGROUND: Ras association domain family 1A (RASSF1A) is a tumor suppressor that regulates the cell cycle, apoptosis, and microtubule stability. The association between the methylation levels of RASSF1A and the prognosis of clear-cell renal cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this relationship to determine the prognostic value of RASSF1A methylation levels for CCRCC. PATIENTS AND METHODS: The study comprised 179 Japanese patients who underwent radical or partial nephrectomy for CCRCC. The methylation level of 5' CpG islands in the RASSF1A was evaluated using combined bisulfite restriction analysis and bisulfite sequencing. RESULTS: High levels of methylation in the RASSF1A promoter were significantly more frequent in grade 3 compared with grade 1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with patients with stage I or II (P = 0.043). Patients with high methylation levels had a significantly less favorable prognosis compared with those with low methylation levels (P = 0.040). Higher methylation levels were independently associated with a poor prognosis following multivariate analysis (P = 0.0053). CONCLUSION: These results indicate that quantitative promoter methylation levels of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.

Multidimensional standard curve for the development process of human fetuses.

The present paper considers a multidimensional view of the standard for the development process of human fetuses. An efficient method by which to find a multidimensional standard curve for the development process of human fetuses is proposed in which a logistic function with three parameters is utilized as an underlying model and a nonlinear regression method is applied. The proposed method also identifies an approximate prediction region, which can be efficiently applied to diagnose fetal malformation.

[Combined aortic root replacement and pectus excavatum correction in Marfan's syndrome].

A 53-year-old man with Marfan's syndrome was admitted for repair of annulo-aortic ectasia (58 mm). He had also severe pectus excavatum. The skin was incised along the sternal midline. The pectoral muscles were detached laterally. After the perichondrium and costal cartilages were resected bilaterally. the left-sided intercostal muscles and perichondrial sheaths were divided 3 cm lateral to the sternum. To place the retractor in parasternal position, excellent exposure of the heart and aortic root was enabled. The aortic root was replaced with a Carboseal graft. Chest wall reconstructions was completed by modified Ravitch procedure with Gore-tex sheet The patient was discharged after an uneventful recovery on postoperative day 14.

Arthroscopic treatment of scaphoid nonunion with humpback deformity and DISI with corticocancellous bone grafting: Technical note.

For two decades, scaphoid nonunion has been treated arthroscopically. However, compressed cancellous bone graft does not have the same mechanical properties as corticocancellous bone graft for reducing the scaphoid humpback deformity and DISI tilt. Here, we describe an arthroscopic technique to treat Alnot stage IIB scaphoid nonunion. We treated a 27-year-old male patient for scaphoid waist nonunion with humpback deformity and DISI. A 8×8×10 mm cylindrical corticocancellous bone graft was harvested from the dorsal aspect of the radius using a single-use osteochondral autograft transfer system (OATS®, Arthrex Inc., Naples, USA). It was inserted in the nonunion site through an arthroscopic volar approach. Bone union was obtained at 3 months with lasting correction of the scaphoid humpback deformity and DISI. The functional result at 6 months was excellent. There were no complications. Scaphoid nonunion with humpback deformity and DISI may be treated arthroscopically with a corticocancellous bone graft.

Relationship between body mass index and periodontitis in young Japanese adults.

BACKGROUND AND OBJECTIVE: Obesity has been implicated as a risk factor for several chronic health conditions. Recent studies have reported a relationship between obesity and periodontitis, but few studies have investigated this relationship in adolescents. The purpose of the present study was to investigate the relationship between body composition (i.e. body mass index and body fat) and periodontitis in university students in Japan. MATERIAL AND METHODS: Medical and oral health data were collected in a cross-sectional examination conducted by the Health and Environment Center of Okayama University. Students aged 18-24 years (n = 618), who were interested in receiving an oral health examination, were included in the analysis. The community periodontal index was used to assess periodontal status. Subjects with a community periodontal index score of 0-2 were considered as controls and those with a community periodontal index score of > 2 were considered to have periodontitis. Logistic regression analysis was used to estimate the association between body mass index and periodontitis. RESULTS: The body mass index of all subjects was < 30 kg/m2. Age and body mass index were significantly associated with the community periodontal index. Logistic regression analysis revealed a 16% increased risk for periodontitis per 1-kg/m2 increase in body mass index (adjusted odds ratio, 1.16; 95% confidence interval, 1.03-1.31; p < 0.05). CONCLUSION: Body mass index could be a potential risk factor for periodontitis among healthy young individuals (i.e. those with a body mass index of < 30 kg/m2). It may be useful to include an evaluation of body mass index on a regular basis in university general and oral health examinations.

[Histoculture drug response assay guided concurrent chemoradiotherapy for non-small cell lung cancer].

Retrospective analysis was done to evaluate concurrent chemoradiotherapy (CCRT) using chemotherapeutic agents judged to be sensitive by histoculture drug response assay (HDRA) for non-small cell lung cancer (NSCLC). We treated 21 NSCLC patients with CCRT using senstivie agents judged by HDRA from 1999 to 2004. Objective response was evaluated in 20 patients. They were consisted of 1 complete response (CR) case, 18 partial response (PR) cases, and 1 stable disease (SD) case. The response rate was 95%. Ten cancer related deaths were observed during 816 +/- 861 (60-2,780) days follow-up. Median survival time was 604 days. One- and 5-year survival rates were 73.9% and 40.3%, respectively. In conclusion, HDRA may improve efficacy of CCRT for NSCLC.

Distal radius fracture fixation with a volar locking plate and endoscopic carpal tunnel release using a single 15mm approach: Feasibility study.

Distal radius fractures (DRF) may trigger, reveal or decompensate acute carpal tunnel syndrome (CTS) in 0.5-21% of cases. Internal fixation and median nerve release must then be carried out urgently. Less invasive approaches have been described for both the median nerve release using an endoscopic device and for the DRF fixation using a volar locking plate. We assessed the feasibility of DRF fixation and median nerve release through a single, minimally-invasive 15mm approach on a series of 10 cases. We reviewed retrospectively 10 consecutive cases of DRF associated with symptomatic CTS in 8 women and 2 men, aged 57 years on average. CTS was diagnosed clinically. All patients were treated during outpatient surgery with a volar locking plate and endoscopic carpal tunnel release using a single 15mm minimally-invasive approach. In one case, arthroscopic scapholunate repair was also required. Six months after the procedure, all patients were reviewed with a clinical examination and a radiological evaluation. The average values for the clinical and radiological outcomes were as follows: pain on VAS 1.5/10; QuickDASH 14.3/100; flexion 90%; extension 90.6%; pronation 95.6%; supination 87.9%; grip strength 90.1%; 2PD test 5.2mm (4-8mm). Five complications occurred: two cases of temporary dysesthesia in the territory of the median nerve and one case of temporary hypoesthesia of the palmar branch of the median nerve, which had all completely recovered; two cases of complex regional pain syndrome type I, which were still active at 6 months. Despite its methodological weaknesses, our study is the only one to describe the technical feasibility of a single 15mm minimally-invasive approach for both internal fixation using a volar locking plate and endoscopic nerve release, with no serious complications. This technique should be added to the surgical toolbox of minimally-invasive procedures for the hand and wrist.

The association of DNA repair gene polymorphisms with the development and progression of renal cell carcinoma.

BACKGROUND: DNA repair enzymes repair some of the DNA damage associated with risk factors for renal cell carcinoma (RCC), including smoking. DNA repair gene polymorphisms modulate the repair capacity and might influence individual risk and progression of RCC. We examined associations between functional polymorphisms and risk, clinicopathologic characteristics and survival of RCC. PATIENTS AND METHODS: The study groups comprised 215 RCC patients and 215 age- and gender-matched healthy controls. Polymorphisms in xeroderma pigmentosum complementation groups C, D and G and X-ray repair cross-complementing groups 1 and 3 genes were genotyped. RESULTS: No significant differences in DNA repair genotype were observed between RCC cases and controls. In all patients, however, greater numbers (> or =3) of total variant alleles in all DNA repair genes studied were associated with less frequent venous extension (P = 0.0079). In smokers, some genotypes were associated with characteristics of RCC (Ps < or = 0.0067) and smokers with greater numbers of total variant alleles had improved overall survival (P = 0.040). CONCLUSION: These results suggest that DNA repair gene polymorphisms may not influence RCC susceptibility, but that some of them may influence RCC progression, especially in smokers, possibly due to altered DNA repair capacity by these polymorphisms.

Detection of new anti-neutral glycosphingolipids antibodies and their effects on Trk neurotrophin receptors.

We screened sera from patients with various neurological disorders for the presence of anti-neutral glycosphingolipids antibodies and only found them in sera from relapsing polychondritis with limbic encephalitis patients. Neutral glycosphingolipids are resident in membrane lipid rafts where high affinity nerve growth factor (NGF) receptor, Trk is co-localized. Therefore, we examined whether these antibodies influence the action of NGF in NGF-responsive cells. The results strongly suggest that these antibodies enhance NGF-induced Trk autophosphorylation and neurite outgrowth as well as neurofilament M expression. These data strongly indicate that these anti-neutral glycosphingolipids antibodies have a functional impact on NGF-Trk-mediated intracellular signal transduction pathway.

Efficacy of gemtuzumab ozogamicin on ATRA- and arsenic-resistant acute promyelocytic leukemia (APL) cells.

Acute promyelocytic leukemia (APL) cells express a considerable level of CD33, which is a target of gemtuzumab ozogamicin (GO), and a significantly lower level of P-glycoprotein (P-gp). In this study, we examined whether GO was effective on all-trans retinoic acid (ATRA)- or arsenic trioxide (ATO)-resistant APL cells. Cells used were an APL cell line in which P-gp was undetectable (NB4), ATRA-resistant NB4 (NB4/RA), NB4 and NB4/RA that had been transfected with MDR-1 cDNA (NB4/MDR and NB4/RA/MDR, respectively), ATO-resistant NB4 (NB4/As) and blast cells from eight patients with clinically ATRA-resistant APL including two patients with ATRA- and ATO-resistant APL. The efficacy of GO was analyzed by (3)H-thymidine incorporation, the dye exclusion test and cell cycle distribution. GO suppressed the growth of NB4, NB4/RA and NB4/As cells in a dose-dependent manner. GO increased the percentage of hypodiploid cells significantly in NB4, NB4/RA and NB4/As cells, and by a limited degree in NB4/MDR and NB4/RA/MDR cells. Similar results were obtained using blast cells from the patients with APL. GO is effective against ATRA- or ATO-resistant APL cells that do not express P-gp, and the mechanism of resistance to GO is not related to the mechanism of resistance to ATRA or ATO in APL cells. Leukemia (2005) 19, 1306-1311. doi:10.1038/sj.leu.2403807; published online 26 May 2005.

Effect of continuous administration of interleukin 2 on active specific chemoimmunotherapy with extracted tumor-specific transplantation antigen and cyclophosphamide.

Injection of purified human interleukin 2 (IL-2) directly into the spleen has been shown to potentiate the effect of specific chemoimmunotherapy, using butanol-extracted tumor-specific transplantation antigen (TSTA) and cyclophosphamide (CY) in a C3H/HeJ murine methylcholanthrene-induced fibrosarcoma model. Since IL-2 has a relatively short half-life in serum, continuous infusion of this lymphokine via the intrasplenic (i.s.), i.v., or i.p. routes was administered in an attempt to maintain therapeutic tissue levels. Primary hosts bearing 7-day (4-mm) or 14-day (greater than 10-mm) established s.c. methylcholanthrene F tumors were treated with weekly s.c. doses of 1 micrograms 1-butanol-extracted, isoelectrophoretically purified TSTA, the first of which was combined with a single i.p. injection of 20 mg/kg CY, and/or a 10-day continuous infusion of 120 units IL-2/day by one of the three routes. IL-2 delivered by all routes either by continuous infusion or by bolus injection augmented the chemoimmunotherapeutic efficacy of TSTA/CY against 7-day established tumors. On the other hand, the outcome of 14-day (greater than 10-mm) established tumors depended upon the method and route of administration of IL-2: continuous infusion via the i.v., i.p., or i.s. route prolonged host survival beyond that obtained by bolus administration. Continuous i.s.-IL-2 infusion greatly prolonged, continuous i.p.-IL-2 (120 units/day) slightly extended, and continuous i.v.-IL-2 had no effect on host survival. In a spontaneous pulmonary metastasis model following amputation of a tumor-bearing limb, only the triple regimen of TSTA/CY/i.s.-IL-2 decreased the number of lung colonies and prolonged host survival. Continuous infusion i.s.-IL-2 (120 units/day, 10 days) combined with TSTA/CY induced tumor-specific cytotoxic T-cells, as documented by in vitro 51chromium release cytolytic and in vivo local adoptive transfer assays. Based upon the residual local adoptive transfer assay activity of spleen cells depleted of specific lymphocyte subpopulations using monoclonal antibodies, the immune effectors generated by i.s.-IL-2 plus TSTA/CY bear the Thy 1+, Lyt2+ phenotype and those by i.p. or i.v.-IL-2 plus TSTA/CY, the Thy+, L3T4+ markers. Thus continuous i.s.-IL-2 infusion appears to augment cytotoxic T-cell induction in tumor-bearing hosts undergoing stimulation of helper elements by TSTA and inhibition of suppressor cells by CY.

Intrasplenic administration of interleukin-2 to potentiate specific chemoimmunotherapy in tumor-bearing mice.

Augmentation of specific chemoimmunotherapy by daily, intrasplenic injection of interleukin-2 (IL-2) was assessed in a methylcholanthrene (MCA)-induced fibrosarcoma model in C3H/HeJ mice. Daily access to the spleen was achieved by relocating the organ into the subcutis while leaving its blood supply intact. Following intrasplenic injection of 80 units of human IL-2 into MCA-F tumor-bearing mice for 6 days, spleen cells tested in the local adoptive transfer assay showed specific neutralization of MCA-F, but not the antigenically different MCA-D, tumor. Depletion of the spleen cell population with monoclonal antibodies and complement showed that the responding cell bore the surface markers Thy 1.2 and Lyt 2. Mice bearing established MCA-F tumors underwent a variety of chemoimmunotherapy regimens, including 1 microgram of 1-butanol, extracted isoelectrophoretically purified tumor-specific transplantation antigen, a single i.p. dose of cyclophosphamide (20 mg/kg), and/or either i.p. or intrasplenic injection of 80 units of IL-2. Specific triple chemoimmunotherapy including daily intrasplenic IL-2, but not i.p., administration was superior in the degree of tumor neutralization to all single or double therapy protocols. Furthermore, the combined triple modality inhibited spontaneous lung colonization by clone 9-4, a highly metastatic variant of MCA-F; both the numbers of lung colonies (median, 17; range, 2 to 55, versus median, 3, range, 0 to 42; P less than 0.005) and the incidence were decreased. The combined treatment group displayed 35% of hosts free of lung metastasis, while 100% of the control animals had lung colonies (P less than 0.02). Thus antitumor immunity was augmented in vivo using IL-2 delivered by intrasplenic, but not i.p., injection. Furthermore, chemoimmunotherapy including intrasplenic IL-2 injection potentiated the antitumor immunity achieved with combined tumor-specific transplantation antigen and cyclophosphamide.

Effects of concomitant and sinecomitant immunity on postsurgical metastasis in mice.

The role of concomitant and sinecomitant antitumor resistance in the regulation of metastatic outgrowth was assessed using methylcholanthrene (MCA)-induced tumors in C3H/HeJ mice. Variants of neoplasms MCA-F, MCA-D, and MCA-2A were selected for proclivity for spontaneous lung metastasis and expression of parental tumor-specific transplantation antigens. The incidence of spontaneous lung metastases after resection of a s.c. tumor of clone 9-4, a highly metastatic variant of the MCA-F tumor, was determined by both the size and the duration of neoplastic disease. The coexistence of the primary local tumor retarded lung colonization both from spontaneous and after artificially induced metastases. Greater concomitant immunity leading to a reduced number of artificial metastases after i.v. challenge with clone 9-4 cells was evident in hosts bearing large (1.6 to 1.8 cm) compared to small (0.1 to 0.2 cm) burdens of the nonmetastatic MCA-F (P less than 0.005). Furthermore, i.v. challenge of mice bearing antigenically different tumors revealed that the concomitant inhibition was antigen specific with small tumor burdens, but nonspecific and possibly more efficacious with large tumor burdens. Therefore, concomitant antimetastatic immunity consists of both specific, immune-mediated resistance and nonimmunological mechanisms. Specific concomitant immunity decreases inversely with the progression of the primary, while nonimmunological inhibition of metastasis increases during late stages of primary growth. Abrogation of the strong nonspecific concomitant inhibition by resection of the primary tumor may facilitate lung metastasis. On the other hand, significantly greater inhibition of metastases occurred after resection of 7- or 14-day neoplasms compared to larger tumors (P less than 0.001 or 0.05). Sinecomitant inhibition is antigen specific, probably representing an extension of specific concomitant immunity. These results suggest that adjunctive immunotherapeutic protocols for surgically treated hosts should augment existent specific immunity and promote nonspecific resistance, in order to minimize metastatic outgrowth.

Suppression of solid tumor growth by immunoneutralizing monoclonal antibody against human basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a potent angiogenic mitogen. To elucidate the effect of bFGF inhibitors in vivo, anti-bFGF immunoneutralizing monoclonal antibody was prepared. One monoclonal antibody against human bFGF, obtained by cell fusion and designated 3H3, completely inhibited bFGF-induced proliferation of human umbilical vein endothelial cells at a concentration of 100 ng/ml. 3H3 did not bind to acidic fibroblast growth factor or HST1 protein, indicating high specificity for bFGF. Furthermore, the immunoneutralizing activity of 3H3 was examined in vivo. K1000 cells (a BALB/c 3T3 transformant in which the leader sequence-fused bFGF gene was transfected) were transplanted s.c. into BALB/c nude mice. Growth of the tumor cells was inhibited by i.v. treatment with 3H3 at a concentration of 200 micrograms/mouse. Histological observation showed that the antitumor effect of 3H3 was due to the inhibition of bFGF-induced angiogenesis. This experiment provides direct causal evidence for the hypothesis that tumor growth is angiogenesis dependent. This finding could also have implications for the development of novel therapeutic approaches to angiogenic solid tumors.

Direct and indirect effects of interferon on in vivo murine tumor cell growth.

We cloned two sublines (S1 and R1) of murine Meth A fibrosarcoma cells with respect to their sensitivity to a murine alpha/beta-interferon (IFN) preparation. The growth of S1 cells was suppressed and that of R1 cells was hardly affected by IFN in vitro. This was also the case with cells enclosed in cell-impermeable diffusion chambers in peritoneal cavities. Nevertheless, IFN suppressed the growth of not only S1 cells but also R1 cells in mice inoculated i.p. with these cells, and the survival rates of both S1 cell recipients and R1 cell recipients were markedly improved. S1 cells were observed microscopically to be injured by the direct effect of IFN in vitro and in vivo, but R1 cells in in vitro culture with IFN and those surviving in vivo in the presence of IFN appeared to proliferate well. In the peritoneal cavity of R1 recipients treated daily with IFN, the recruitment of macrophages was enhanced in comparison with untreated R1 recipients. Adherent peritoneal exudate cells obtained from IFN-treated, R1-bearing mice were highly suppressive for the in vitro growth of not only R1 cells but also allogeneic and human cells. The role of macrophages in the indirect effect of IFN on tumor cell growth is discussed.