Spontaneous oral tumours in 18 rabbits (2005-2015).

This retrospective study of a series of 18 cases aimed to describe the clinical and pathological findings of oral tumours in rabbits, as there have been few reports detailing spontaneous oral tumours in this species. A total of 13 different tumour types were diagnosed: squamous cell carcinoma (three), ameloblastoma (two), fibrosarcoma (two), osteosarcoma (two), cementoma (one), complex odontoma (one), giant cell epulis (one), sarcoma (one), chondrosarcoma (one), trichoepithelioma (one), papilloma (one), malignant melanoma (one) and basal cell carcinoma (one). Odontogenic tumours were relatively common in this study as compared to the oral tumours typically identified in dogs and cats. The most common clinical sign in this study was feeding abnormalities. Surgical excision and radiation therapy were found to be effective in rabbits.

Spontaneous intranasal tumours in rabbits: 7 cases (2007-2019).

OBJECTIVES: Neoplasms that arise in the nasal cavity are reported infrequently in rabbits. This case series aims to review and determine the clinical behaviour of neoplasms in the nasal cavity in rabbits. MATERIALS AND METHODS: A retrospective study was conducted on seven pet rabbits diagnosed with intranasal tumours to describe the clinical and histopathological findings and prognoses after surgery and/or radiotherapy. RESULTS: The most common clinical signs were nasal snoring when breathing, nasal discharge, and subsequent dyspnoea and anorexia. Six different histopathological types of tumours were diagnosed: intranasal adenocarcinoma, squamous cell carcinoma, osteosarcoma, carcinoid tumour, osteoma, and lymphoma. Skull radiography only revealed the abnormalities in three of seven cases but on CT, the intranasal masses were more clearly identified in all cases. All cases received tumour resection through rhinostomy and four cases received radiotherapy after surgery. In the six cases with a known outcome, the survival time after surgery was more than 13 months. CLINICAL SIGNIFICANCE: This case series provides an insight of the behavior of intranasal neoplasms in rabbits. Surgical treatment and radiotherapy could improve their clinical sings.

Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor beta chain.

The interleukin-2 receptor beta chain (IL-2R beta) is expressed on a variety of hematopoietic cell types, including natural killer (NK) cells and nonconventional T lymphocyte subsets such as intestinal intraepithelial lymphocytes (IEL). However, the importance of IL-2R beta-mediated signaling in the growth and development of these cells has yet to be clearly established. We have investigated IEL and NK cells in mice deficient for IL-2R beta and describe here striking defects in the development of these cells. IL-2R beta-/- mice exhibited an abnormal IEL cell population, characterized by a dramatic reduction in T cell receptor alpha beta CD8 alpha alpha and T cell receptor gamma delta lymphocytes. This selective decrease indicates that IEL can be classified into those whose development and/or differentiation is dependent on IL-2R beta function and those for which IL-2R beta-mediated signaling is not essential. NK cell development was also found to be disrupted in IL-2R beta-deficient mice, characterized by a reduction in NK1.1+CD3- cells in the peripheral circulation and an absence of NK cytotoxic activity in vitro. The dependence of NK cells and certain subclasses of IEL cells on IL-2R beta expression points to an essential role for signaling through this receptor, presumably by IL-2 and/or IL-15, in the development of lymphocyte-subsets of extrathymic origin.

Positive selection of extrathymically developed T cells by self-antigens.

Most T cells develop through the thymus, where they undergo positive and negative selection. Some peripheral T cells are known to develop in the absence of thymus, but there is insufficient information about their selection. To analyze the selection of extrathymically developed T cells, we reconstituted thymectomized male or female recipient mice with bone marrow cells of mice transgenic for male H-Y antigen-specific T cell receptor (TCR). It was revealed that the T cells bearing self-antigen-specific TCR were not deleted in thymectomized male recipients. More importantly, the absence of H-Y antigen-specific T cells in thymectomized female recipients suggests positive selection of extrathymically developed T cells by the self-antigen. The extrathymically developed T cells in male mice expressed interleukin (IL)-2 receptor beta chain (IL-2Rbeta) and intermediate levels of CD3 (CD3(int)) but were natural killer cell (NK)1.1(-). They rapidly produced interferon gamma but not IL-4 after TCR cross-linking. Furthermore, a similar pattern of cytokine production was observed in CD3(int)IL-2Rbeta+NK1.1(-) cells in normal mice which have been shown to develop extrathymically. These results suggest that extrathymically developed CD3(int)IL-2Rbeta+NK1. 1(-) cells in normal mice are also positively selected by self-antigens.

Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes.

The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/-) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross-linking. SEK1(-/-) peripheral T cells showed decreased proliferation and IL-2 production after CD28 costimulation and PMA/Ca2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1(-/-)RAG2(-/-) chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca2+ ionophore stimulation, which mimics TCR-CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1(-/-) mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1(-/-) thymocytes failed to induce SAPK/JNK in response to PMA/Ca2+ ionophore, SEK1(-/-)RAG2(-/-) thymocytes proliferated and made IL-2 after PMA/Ca2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1(+/+)RAG2(-/-) thymocytes, implying that CD28 costimulation and PMA/Ca2+ ionophore-triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL-2 production and T cell proliferation.

Folate intakes and folate biomarker profiles of pregnant Japanese women in the first trimester.

OBJECTIVE: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women in early pregnancy. DESIGN: A cross-sectional, observational study. SUBJECTS: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were not consuming any folate supplements or folate fortified foods. METHODS: Three-day dietary records were obtained from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers. Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate group (serum folate > or = 9 ng/ml). RESULT: Mean serum and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels were remarkably higher than the reported values from many other countries despite our subjects receiving no folic acids supplements. However, mean folate intake by our subjects from natural foods was 289 microg/day, which is thought to be low according to the Japanese dietary recommendation specified for pregnant women. The intake of spinach and fruits was significantly greater in the high folate group than in the low folate group. CONCLUSION: Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in Japanese pregnant women in the first trimester, although the intake of folate from natural food was not high enough to meet the recommended daily intake.

Maternal weight gain ranges for optimal fetal growth in Japanese women.

OBJECTIVE: To identify adequate weight gain ranges during pregnancy in Japanese women. METHOD: Obstetric records from 2001 to 2002 for 46,659 term, singleton, vaginally delivered live births was used to estimate IUGR and macrosomia risk. Total maternal weight gain was grouped according to gestational age-specific percentile values of weight gain as follows: "very low" (under the 25th), "low" (25th to 49th), "moderate" (50th to 74th), "high" (75th to 89th), and "very high" (90th and over). RESULTS: About 6% of infants were identified as having IUGR and 0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk was related to high weight gains and previous spontaneous abortions. CONCLUSION: Achieving weight gains between the 50th and 75th percentiles for gestational age was considered adequate for optimal fetal growth in Japanese pregnant women.

Autoreactive and heat shock protein 60-recognizing CD4+ T-cells show antitumor activity against syngeneic fibrosarcoma.

A CD4+ heat shock protein (hsp) 60-recognizing autoreactive T-cell line (BASL1) and clone (BASL1.1) were examined for their antitumor activity against major histocompatibility complex class II- syngeneic Meth A fibrosarcoma (Meth A), which was immunofluorescently stained with monoclonal antibody specific for hsp 60. In in vitro proliferative assay, BASL1.1 was suggested to recognize Meth A-derived hsp 60 presented by syngeneic antigen-presenting cells in a major histocompatibility complex class II-restricted manner. This cell line and clone showed antitumor activity in tumor-neutralizing (Winn) assay. BASL1 and BASL1.1 cells produced gamma-interferon, tumor necrosis factor, and interleukin 2 but not interleukin 4 by the stimulation with syngeneic spleen cells. In cytolytic assay, these cell lines and clones showed neither direct nor indirect (bystander) cytolysis against Meth A. In cytostatic assay, these cells inhibited the proliferation of Meth A in the presence of syngeneic macrophages, and this activity was abrogated by the addition of anti-gamma-interferon monoclonal antibody. Recombinant gamma-interferon could induce cytostatic activity only in the presence of macrophages, and tumor necrosis factor synergized this activity. Antitumor activity induced by BASL1 was abrogated by the administration of anti-CD8 monoclonal antibody in vivo, suggesting that CD8+ cytotoxic T-lymphocytes are essential and final effector cells for BASL1-mediated Meth A rejection. These findings indicate that CD4+ autoreactive and hsp 60-recognizing T-cells show two types of antitumor activity: cytostasis and induction of tumor-specific cytotoxic T-lymphocytes. Furthermore, these results imply that tumor-specific immunity could be elicited by CD4+ helper T-cells which recognize hsp.

Characterization of a Rana catesbeiana lectin-resistant mutant of leukemia P388 cells.

Sialic acid-binding lectin (SBL-C) from Rana catesbeiana eggs inhibits the growth of tumor cells such as P388 and L1210 leukemia cells (K. Nitta et al., Cancer Res., 54: 920-927, 1994). Here we report the establishment of an SBL-resistant P388 variant cell line, RC-150. Both P388 and RC-150 cells were agglutinated by SBL-C; however, growth of RC-150 cells was unaffected by SBL-C. Cytoplasmic free Ca2+ concentration and transglutaminase activity of RC-150 cells were 0.5 (110 nM) and 3 times (0.62 nmol/mg/min) as high as those of P388 cells, respectively. Microvilli and microplicae were observed on the surface of P388 cells by scanning electron microscopy but were rarely seen on RC-150 cells. Dansylcadaverine-labeled SBL-C bound to both P388 and RC-150 cells. Binding of SBL-C to these tumor cells appears to be mediated by two species of wheat germ agglutinin-stained cell membrane sialoglycoproteins. Labeled SBL-C entered P388 but not RC-150 cells, suggesting that internalized SBL-C acts as an inhibitor of cell proliferation.

Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia.

Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies.

Clonal evolution to acute myeloblastic leukemia with MLL gene rearrangement from trisomy 8 clone.

A 20-year-old Japanese man was referred because of severe pancytopenia with 14% of abnormal blasts in hypocellular bone marrow. After treatment by granulocyte colony-stimulating factor (G-CSF) and transfusions of red blood cells, spontaneous remission was subsequently achieved. After 3 months' remission, however, the patient developed AML characterized by the abnormal karyotype: 46XY,+8,t(9;11)(p22;q23). FISH study revealed the presence of trisomy 8 clone also in the hypoplastic state. While MLL-AF9 chimeric mRNA was observed in leukemic cells, it was not detectable in bone marrow cells from the hypoplastic state by RT-PCR. This is the first report of a trisomy 8 clone which evolved into one with a MLL gene rearrangement.

MAT-1, a monoclonal antibody that specifically recognizes human tyrosinase.

There is no available monoclonal antibody which reacts specifically recognizes human tyrosinase. Employing a synthetic peptide, MEKEDYHSLYQSHL, corresponding to the carboxyl terminus of human tyrosinase as an immunogen, we produced a mouse monoclonal antibody MAT-1 of the IgG1 isotype. The epitope for MAT-1 was determined to be EDYH, the sequence of which is not present in human tyrosinase-related protein-1 (TRP-1) or tyrosinase-related protein-2 (TRP-2). By transient expression assays and immunofluorescence technique, we show that MAT-1 reacts specifically with cells expressing human tyrosinase cDNA but not with cells expressing TRP-1 or TRP-2 cDNA. The results of immunohistochemical staining also confirmed that MAT-1 reacts specifically with epidermal melanocytes in human skin sections. MAT-1 should be invaluable for studying the interaction between tyrosinase and TRPs and for detecting the changes in the levels of tyrosinase expression. In addition, MAT-1 should be useful as a sensitive immunohistochemical tool for investigation of various pigmentary disorders and possibly for the diagnosis of melanoma.

Localization of rat FGF-5 protein in skin macrophage-like cells and FGF-5S protein in hair follicle: possible involvement of two Fgf-5 gene products in hair growth cycle regulation.

It has been reported that the gene for murine fibroblast growth factor-5 (Fgf-5) is expressed in the rat hair follicle and that this expression may be associated with catagen induction (Hebert et al, 1994). In this study, we analyzed the Fgf-5 gene product in skin because the gene generates two mRNA that translate into the FGF-5 protein and a short form of the FGF-5 protein (FGF-5S) as a result of an alternative splicing (Hattori et al, 1996; Ozawa et al, 1996). Indeed, we detected both types of FGF-5 mRNA in rat skin samples. Two monoclonal anti-FGF-5 antibodies, one (E723) being specific for FGF-5 long-form protein and the other (B2B6) being reactive with both FGF-5 and FGF-5S proteins, were used to locate these proteins by immunohistochemistry. Staining of the rat skin revealed that only the B2B6 antibody reacted with hair follicles and that both antibodies reacted with macrophage-like round cells, suggesting that the product of the Fgf-5 gene in the hair follicle is FGF-5S. The immunoreactivity of the FGF-5S protein increased during early anagen VI and decreased rapidly during catagen. The density of FGF-5-positive macrophage-like cells in the dermis increased during anagen and decreased during catagen and telogen, whereas the density of these cells in the panniculus adiposus did not change during anagen and increased during catagen and telogen. There was no apparent association between the density of FGF-5-positive macrophage-like cells and that of FGF-5-negative, dendritic macrophage-like cells. Thus, the results suggest the possible involvement of FGF-5S in the hair follicle in anagen VI and catagen development and that the density of FGF-5-positive macrophage-like cells may also be associated with the hair growth cycle.

Structure of the human retinoblastoma-related p107 gene and its intragenic deletion in a B-cell lymphoma cell line.

The human p107 protein shares many structural and functional features with the retinoblastoma gene product and retinoblastoma-related p130 protein. In this study, we have cloned and elucidated the complete intron-exon organization of the gene encoding the p107 protein. The gene contains 22 exons spanning over 100kilobase pairs of genomic DNA. The length of individual exons ranges from 50 to 840base pairs. The arrays of exons in the p107 gene are rather similar among members of the gene family, especially to those of the p130 gene, while the length of introns is extensively diverse. This study will provide a molecular basis for implementing comprehensive screening for p107 mutations using genomic DNAs from human malignancies. We also show a detailed structure of an intragenic deletion of the p107 gene found in a human B-cell lymphoma cell line, KAL-1, which was shown to occur by homologous recombination between the two directly repeated Alu family sequences.

Effect of chemical modification at C1 of the glucosamine backbone of lipid A-subunit analog GLA-27 on manifestation of immunopharmacological activity.

The effect of chemical modification at the C1 position of GLA-27, 4-O-phosphono-D-glucosamine carrying N-3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] and 3-O-tetradecanoyl (C14) groups, was investigated. Replacement by SH or S-acetyl groups of the OH group resulted in the enhancement of mitogenicity but gave rise to a reduction, in macrophage-stimulating ability such as induction of tumor necrosis factor and enhancement of phagocytic and cellular acid phosphatase activities. Bisphosphorylation at C1 and C4 resulted in a slight decrease in mitogenicity or almost complete loss of the macrophage-stimulating ability.

Mycobacterial cord factor, but not sulfolipid, causes depletion of NKT cells and upregulation of CD1d1 on murine macrophages.

Trehalose 6,6'-dimycolate (TDM, cord factor) has frequently been used as an adjuvant to stimulate antibody production. Although it also induces cellular immunity, detailed studies about the underlying events do not exist. To determine the kinetics of TDM-specific changes promoting a T helper 1 (Th1) response, we injected mice with TDM or 2,3,6,6'-tetraacyl trehalose 2'-sulfate (SL, sulfolipid), another mycobacterial trehalose-containing glycolipid without mycolic acid. TDM, but not SL, caused a strong increase in serum interferon-gamma (IFN-gamma) levels 2 days later, accompanied by expansion of natural killer (NK) cells. Subsequent TDM effects included depletion of normal-density CD4(+) NK1.1(+) TCRalpha/beta(intermediate) cells from day 7 on, upregulation of MHC class II and CD1d1 on macrophages (peaking on day 21), and an increased proportion of Th1 cells evident after 3 weeks. TDM, but not a similar glycolipid without mycolic acid, can therefore initiate a cascade of events starting with strong release of IFN-gamma and NK cell expansion, resulting in the appearance of macrophages activated for antigen presentation. Our data therefore provide the basis for optimized immunization schedules with TDM as the adjuvant component of a Th1 vaccine.

Hematopoietic progenitor cells from allogeneic bone marrow transplant donors circulate in the very early post-transplant period.

Despite the therapeutic efficacy of allogeneic bone marrow transplantation (allo-BMT), circulating hematopoietic progenitor cells after bone marrow transplantation have not been well characterized. In the present study, we focused on these 'post-transplant circulating progenitor cells (PTCPC)' which may be on their way to bone marrow. We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just before transplantation), 1 (8-15 h after the completion of transplantation), 2, 3, 5, 7, 10, 14, 17, 21, 28 and 35 after allo-BMT in five transplant patients using a standard methylcellulose assay. In addition, high proliferative potential colony-forming cells (HPP-CFC) of the harvested donor bone marrow (BM) and day 1 PB of recipients were assayed in five patients. The origin of HPP-CFC from day 1 PB was analyzed by polymerase chain reaction of a DNA region containing a variable number of tandem repeats. The replating potential of these HPP-CFC was evaluated by a secondary colony assay. The proportion of CD38negative cells among CD34+ cells in the harvested BM and day 1 PB was evaluated by two-color flow cytometric analysis. The number of CFU-GM on day 1 ranged from 6 to 73/10 ml PB, and became undetectable on day 5. The reappearance of PTCPC was observed on day 14, along with hematopoietic recovery. The proportion of HPP-CFC among myeloid colonies from day 1 PB was significantly higher than that from harvested BM (44.3+/-10.4% vs 11.3+/-2.1%, respectively, n=5, P=0.0030). These HPP-CFC from day 1 PB were confirmed to be of donor origin. More than 90% of these HPP-CFC had replating potential. Two-color flow cytometric analysis revealed that the proportion of CD34+CD38negative cells was significantly higher in day 1 PB than in the harvested BM (61.0+/-16.5% vs 9.3+/-3.5%, respectively, n=7, P=0.0002). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following allo-BMT.

Plasma aldosterone response to angiotensin II in sodium-restricted elderly subjects with essential hypertension.

The plasma aldosterone (PA) response to sodium restriction (25 mEq daily for 4 days) and to graded infusions of angiotensin II (AII, 2, 4 and 8 ng/kg/min each for 30 min) during a low-sodium intake were studied in 15 elderly subjects with mild essential hypertension versus 10 elderly normotensive subjects. The PA response to sodium restriction relative to changes in plasma renin activity (PRA) was estimated by the ratio of PA increment to PRA increment after sodium restriction (delta PA/delta PRA). THe PA response to graded AII infusions was determined by the increment of PA above the basal level after each dose of AII. In 10 of the 15 elderly hypertensive subjects whose PRAs responded normally to sodium restriction, the delta PA/delta PRA ratios and PA increments during the graded AII infusions were similar to those in the elderly normotensive subjects. However, in the remaining 5 elderly hypertensive subjects whose PRAs responded subnormally to sodium restriction, the delta PA/delta PRA ratios were high and the PA increments greater during the graded AII infusions. THe increments of mean blood pressure during the graded AII infusions were similar in the foregoing 10 of 15 hypertensive subjects, and significantly greater during the AII infusion rates of 4 and 8 ng/kg/min in the remaining 5 hypertensive subjects when compared with those in the normotensive subjects. Apparently some subjects with essential hypertension, whose PRAs response subnormally to sodium restriction, have an abnormally enhanced adrenal responsiveness to AII under the conditions of low-sodium intake.

MR appearance of the persistent hypoglossal artery.

We describe the MR appearance of the persistent hypoglossal artery incidentally found in a case of known glioblastoma multiforme. On the spin-echo images, an abnormal tubular structure of low intensity penetrating the hypoglossal canal was recognized. MR angiography showed its vascular nature and the anomalous vessel connecting the internal carotid and basilar arteries.

Application of a rigid endoscope to the microsurgical management of 54 cerebral aneurysms: results in 48 patients.

OBJECT: To enhance visual confirmation of regional anatomy, endoscopy was introduced during microsurgery for cerebral aneurysms. The risks and benefits are analyzed in the present study. METHODS: The endoscopic technique was used during microsurgery for 54 aneurysms in 48 patients. Forty-three aneurysms were located in the anterior circulation and 11 were in the posterior circulation. Thirty-eight aneurysms (70.4%) had not ruptured. All ruptured aneurysms in the present series produced Hunt and Hess Grade I or II subarachnoid hemorrhage. After initial exposure achieved with the aid of a microscope, the rigid endoscope was introduced to confirm the regional anatomy, including the aneurysm neck and adjacent structures. The necks of 43 aneurysms were clipped using microscopic control or simultaneous microscopic/endoscopic control. After clipping, the positions of the clip and nearby structures were inspected using the endoscope. Use of the neuroendoscope provided useful information that further clarified the regional anatomy in 44 cases (81.5%) either before or after neck clipping. In nine cases (16.7%), these details were available only with the use of the endoscope. In five cases (9.3%), the surgeons reapplied the clip on the basis of endoscopic information obtained after the initial clipping. There were two cases in which surgical complications were possibly related to the endoscopic procedures (one patient with asymptomatic cerebral contusion and another with transient oculomotor palsy). CONCLUSIONS: It is the authors' impression that the use of the endoscope in the microsurgical management of cerebral aneurysms enhanced the safety and reliability of the surgery. However, there is a prerequisite for the surgeon to be familiar with this instrumentation and fully prepared for the risks and inconveniences of endoscopic procedures.