Removal of a cavernous hemangioma in the orbital apex via the endoscopic transnasal approach: a case report.

INTRODUCTION: The aim of this study is to describe the case of a cavernous hemangioma extending from the orbital apex to the pterygopalatine fossa that was completely removed via an endoscopic transnasal approach. CASE REPORT: We report the case of a 48-year-old man who presented with right hemianopsia of the left eye. MRI revealed a 1.5 x 1.1 cm mass lesion extending from the infero-medial part of the left orbital apex to the pterygopalatine fossa. Removal of the lesion was performed via the endoscopic transnasal approach. Using this approach, a wide operative view of the entire extent of the lesion from the optic canal to the orbital apex and the pterygopalatine fossa was obtained, and complete removal of the lesion was performed safely. The pathological diagnosis was cavernous hemangioma. CONCLUSION: The endoscopic transnasal approach is a safe, effective, and less invasive therapeutic modality for the removal of lesions extending from the infero-medial part of the left orbital apex to the pterygopalatine fossa. With appropriate patient selection, this approach improves access and visualization, and it enables performance of operative procedures with much less risk than the conventional microscopic transcranial or transfacial approaches.

Protein kinase C mRNA and protein expressions in hypobaric hypoxia-induced cardiac hypertrophy in rats.

AIM: Protein kinase C (PKC), cloned as a serine/threonine kinase, plays key roles in diverse intracellular signalling processes and in cardiovascular remodelling during pressure overload or volume overload. We looked for correlations between changes in PKC isoforms (levels and/or subcellular distributions) and cardiac remodelling during experimental hypobaric hypoxic environment (HHE)-induced pulmonary hypertension. METHODS: To study the PKC system in the heart during HHE, 148 male Wistar rats were housed for up to 21 days in a chamber at the equivalent of 5500 m altitude level (10% O(2)). RESULTS: At 14 or more days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased. In the right ventricle (RV): (1) the expression of PKC-alpha protein in the cytosolic and membrane fractions was increased at 3-14 days and at 5-7 days of exposure respectively; (ii) the cytosolic expression of PKC-delta protein was increased at 1-5, 14 and 21 days of exposure; (3) the membrane expressions of the proteins were decreased at 14-21 (PKC-betaII), 14-21 (PKC-gamma), and 0.5-5 and 21 (PKC-epsilon) days of exposure; (4) the expression of the active form of PKC-alpha protein on the plasma membrane was increased at 3 days of exposure (based on semiquantitative analysis of the immunohistochemistry). In the left ventricle, the expressions of the PKC mRNAs, and of their cytosolic and membrane proteins, were almost unchanged. The above changes in PKC-alpha, which were strongly evident in the RV, occurred alongside the increase in PAP. CONCLUSION: PKC-alpha may help to modulate the right ventricular hypertrophy caused by pulmonary hypertension in HHE.

Interleukin-1 receptor-related protein ST2 suppresses the initial stage of bleomycin-induced lung injury.

Acute lung injury has a range of causes, and occasionally leads to lethal respiratory failure. Despite advances in treatment, acute lung injury continues to have a high mortality rate, and thus a new therapeutic approach is needed. ST2 is an interleukin (IL)-1 receptor-related protein, and its expression is induced by various inflammatory responses. Recently, ST2 has been speculated to exert anti-inflammatory effects; therefore, we investigated the role of the ST2 in the murine model of acute lung injury. To elucidate the function of ST2 in vivo, mice that transiently overexpressed ST2 protein were prepared using the hydrodynamic gene transfer method, and lung injury was induced by intratracheal administration of bleomycin. In bleomycin-treated ST2-overexpressing mice, the increase of neutrophils in the bronchoalveolar lavage fluid (BALF) was markedly suppressed. Additionally, the levels of tumour necrosis factor-alpha and IL-6, as well as the concentration of albumin, in BALF were reduced compared with those of controls. Furthermore, the pulmonary architecture in ST2-overexpressing mice remained almost normal, and the survival rate was significantly improved. From these results, we concluded that ST2 has the potential to suppress the initial stage of acute lung injury, and therefore it may be a useful reagent for the treatment of acute lung injury.

Osteopontin expression in normal and hypobaric hypoxia-exposed rats.

AIM: Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart and pulmonary arteries. Osteopontin (OPN) has emerged as a key factor in cardiovascular remodelling in response to pressure or volume overload. We studied the possible effects of HHE on the OPN synthesis system. METHODS: One hundred and forty-eight male Wistar rats were housed in a chamber with conditions equivalent of an altitude of 5500 m for up to 21 days. RESULTS: Plasma OPN protein level was found to be significantly decreased on day 0.5 of exposure to HHE, as was the level in the adrenal gland (which secreted highest levels of OPN protein). In the right ventricle of the heart (mRNA) and the lung (protein), OPN expression was found to be significantly increased only on day 1 and day 5, respectively, of exposure to HHE. By immunohistochemistry, the distribution and intensity of OPN protein in several organs were found to alter during exposure to HHE. However, these changes in OPN synthesis did not coincide with the moderate increase in pulmonary arterial pressure (PAP) (maximal mean PAP, 24.5 mmHg) during HHE. CONCLUSION: Pulmonary hypertension in HHE with conditions equivalent of an altitude of 5500 m may induce little or no OPN in heart and lung. Sustained induction may require a more severe PAP overload.

Inner-ear obliteration in ulcerative colitis patients with sensorineural hearing loss.

OBJECTIVE: Systemic autoimmune diseases, including ulcerative colitis, may involve the inner ear. Several ulcerative colitis cases presenting with sensorineural hearing loss have been reported. We report the T2-weighted, three-dimensional, inner-ear magnetic resonance imaging findings in the inner ears of two such patients. METHODS: Case reports and a review of the literature concerning autoimmune disease and sensorineural hearing loss are presented. RESULTS: We describe two cases of ulcerative colitis with sensorineural hearing loss in which three-dimensional magnetic resonance imaging revealed obliteration of the inner ear. Those inner ears with obliteration had severe hearing loss, and responded poorly to steroid therapy. CONCLUSION: To our knowledge, there has been no previous published report of the T2-weighted, inner-ear magnetic resonance imaging findings of cases of ulcerative colitis with sensorineural hearing loss. This paper represents the first published report in the world literature of inner-ear obliteration in such patients. Three-dimensional magnetic resonance imaging is beneficial in elucidating the pathophysiology of the inner-ear involvement seen in ulcerative colitis.

Lack of B-RAF mutations in head and neck squamous cell carcinoma.

B-RAF is one of the most commonly mutated oncogenes in human cancer. However, the mutation status of B-RAF has not been established completely in HNSCC. We have analysed the mutation status of the kinase domain of the B-RAF gene (exons 11 and 15) in 91 Japanese HNSCC patients as well as 12 HNSCC cell lines. DNA was extracted and amplified by PCR. Mutations were then analysed by SSCP mutation detection method. Since V600EB-RAF constitutes 90 % of the mutations identified in B-RAF in human cancers, we also used MASA analysis to specifically detect this mutation in exon 15 of B-RAF. Using both methods, no mutation was found in both exon 11 and 15 in all patients and cell lines. Mu tations are absent or rare in the kinase domain of B-RAF in Japanese HNSCC. However, more studies are still needed to determine its usefulness as a target for molecular therapy in these patients.

Continuous infusion of 5-fluorouracil with versus without low-dose, consecutive administration of cisplatin in advanced colorectal cancer. A prospective randomized phase II study.

Recently, the treatment of advanced gastric cancer by continuous infusion of 5-fluorouracil (5-FU) with low-dose cisplatin (CDDP) has improved efficacy without severe toxicities. The possible effectiveness of 5-FU+low-dose CDDP for colorectal cancer (CRC) is intriguing. One hundred fifty-five patients with far-advanced CRC including at least one measurable lesion were enrolled in a prospective randomized clinical trial funded by the Japanese Foundation for Multidisciplinary Treatment of Cancer. These patients were assigned to the two arms to assess the value of low-dose CDDP when added to a continuous intravenous infusion of 5-FU at a dose of 300 mg/m(2)/24 hrs in a one-week cycle consisting of 5 days of treatment and 2 days of rest for at least 12 weeks. CD-DP was given intravenously at a dose of 3 mg/m(2) on days 1-5 and days 8-12, and then at a dose of 7 mg/m(2) twice a week. Three patients were excluded from the trial. The response rate in the 5-FU+low-dose CDDP arm (n=75) was significantly higher than that in the 5-FU arm (n=77) (25.3% vs. 11.7%; P = 0.037). There was no significant difference in the median overall survival time between the 5-FU+low-dose CDDP arm and the 5-FU arm (479 and 491 days, respectively). Grades 3/4 toxicities occurred infrequently in both arms. The quality of life was almost the same between the arms. Low-dose CDDP improved the response rate while keeping toxicities within clinically acceptable limits. However, this combined treatment did not confer a survival advantage over treatment with continuous infusion of 5-FU alone for patients with far-advanced CRC; that might be attributable to the short CDDP administration setting of 12 weeks.

Elevation of ST2 protein levels in cerebrospinal fluid following subarachnoid hemorrhage.

OBJECTIVE: To study the mode of appearance of ST2 in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Immunoprecipitation and subsequent immunoblotting were performed to reveal the existence of ST2 in CSF after SAH. CSF samples from 21 patients were analyzed for ST2 using an enzyme-linked immunosorbent assay system. The ST2 levels were compared between serum and CSF after SAH. The ST2 levels in CSF were measured in six patients operated with other than SAH. RESULTS: ST2 was secreted into CSF after SAH. The concentration of ST2 was the highest in the samples of the first post-operative day and declined thereafter. The patients operated with other than SAH did not show the elevation of ST2 in CSF. CONCLUSIONS: This study revealed the presence of ST2 in CSF for the first time and suggested a possibility that ST2 is related to the inflammatory reaction in the central nervous system after SAH.

Irrigation-suction straw sheath system for a rigid endoscope during endonasal endoscopic pituitary surgery.

OBJECTIVE: One of the most problematic conditions during endonasal endoscopic pituitary surgery is blurred endoscopic vision caused by blood or bone dust. To address this problem we used a new device, the irrigation-suction straw sheath system originally developed for endoscopic sinus surgery in rhinology, for the endoscopic pituitary surgery. METHODS: The irrigation-suction straw system (K-endosheath; Koken Co., Tokyo, Japan) consists of a flattened disposable straw catheter which can be attached on a rigid endoscope. When the endoscope is inserted into the oblong catheter, two gaps remain on either side of the endoscope. Through each of these gaps irrigation and continuous suction are performed respectively. RESULTS: Clear vision could be immediately obtained by pressing the button to release the irrigation water onto the endoscope's front lens. Even targeted irrigation during drilling was possible. Above all, continuous suction was useful to clear the operative field of blood, smoke, or bone dust, ensuring the safety and uninterrupted progress of the procedure. CONCLUSION: This irrigation-suction system has proved to be very useful and easy to use for endonasal endoscopic pituitary surgery. Further development of such new devices and instruments specialized for endonasal endoscopic pituitary surgery will promote the increased use of this minimally invasive technique in neurosurgery.

A newly designed disposable introducer sheath for a ventricular fiberscope.

We have developed a disposable plastic introducer sheath for use with a flexible endoscope during intraventricular procedures. The sheath is composed of a thin polypropylene tube passing through the center of a plastic stopper. The tube serves as a sheath through which the fiberscope is introduced into the ventricle. The stopper seats in the burr hole and prevents downward and lateral movement of the tube. The sheath can be placed safely in the ventricle with a drainage catheter used as an introducing guide. We used this sheath system in 10 patients and found it very useful. Manipulation of the fiberscope was not hindered, copious irrigation was allowed, and the sheath remained stable on the skull. This new introducer sheath may contribute to the increased use of a flexible endoscope in neuroendoscopic procedures.

Smoking and polymorphisms of fucosyltransferase gene Le affect success of H. pylori eradication with lansoprazole, amoxicillin, and clarithromycin.

Identification of factors influencing success of Helicobacter pylori (HP) eradication is important for clinical practice. We have prospectively conducted an HP eradication study in the Aichi Cancer Center with a total of 142 patients available for analysis. The overall success rate was 61.3% (95% confidence interval 52.7-69.3%). Smoking during the medication for eradication significantly decreased the success rate (42.9%), whereas smoking cessation during the treatment was associated with a similar rate as for non-smokers (66.7%). We also examined links between an eradication outcome and polymorphisms of Le, Se, IL1A, IL1B, IL1RN and MPO genes, but with one exception none showed any association. The non-functional le allele of Le polymorphisms, leading to decreased expression of Le(b) antigen to which HP attaches with adhesin, showed a beneficial effect for success. Although further clarification is necessary, our study indicated that smoking cessation and Le gene polymorphisms may affect the success rate of HP eradication.

Dry matter accumulation in citrus fruit is not limited by transport capacity of the pedicel.

The vascularization of the pedicel in Marisol clementine (Citrus clementina Hort. ex Tanaka) has been characterized in relation to fruit growth. Phloem and xylem formation occurred during the first half of the period of fruit growth. Phloem cross-sectional area reached its maximum value by the end of fruitlet abscission, 78 d after anthesis (DAA), shortly after the rate of accumulation of dry matter in fruitlets reached its maximum value. Secondary xylem formation occurred until day 93, well after the end of fruitlet abscission. At fruit maturity, xylem accounted for 42-46 % of the cross-section of the pedicel. Vessels differentiated in this late-formed xylem. Formation of phloem and early xylem was directly related to fruitlet size (and growth rate). Differences in the rate of formation of conductive tissues in the pedicel of the developing fruitlets followed rather than preceded the differences in growth rate. Specific mass transfer (SMT) in the phloem was highest in the fastest growing fruitlets, and peaked during the late stages of fruitlet abscission (72-78 DAA) and during the main period of fruit growth (107-121 DAA). Application of a synthetic auxin to developing fruits, either at the end of flowering (2,4-D) or by day 64 after flowering (2,4-DP), increased the growth rate of the fruit and fruit size at maturity (8-13 % increase in fruit diameter at maturity). These auxin applications also enhanced the formation of conductive tissues in the pedicel, with a specific effect on phloem formation. Applying auxin at flowering resulted in a reduction in the phloem SMT by days 72-78, whereas auxin application on day 64 increased this parameter. Despite this difference in behaviour, which resulted from the different time-course of the growth response of the fruit to auxin applications, these applications increased fruit size to a similar extent. Severing 37 % of the phloem of the pedicel during the main period of fruit growth resulted in an increase in the specific mass transfer in the phloem but had no influence on fruit growth. These observations demonstrate that the transport capacity in the phloem of the pedicel does not limit fruit growth and, within the limits of our experiments, an increase in demand by the fruit appeared to be matched by an increase in SMT. The dependence of late xylem formation (after the period of fruitlet abscission) on fruitlet growth was demonstrated in Salustiana orange [Citrus sinensis (L.) Osbeck] by means of controlling fruit growth through the manipulation of leaf area. Fruit growth at this time was more closely related to leaf area than to carbohydrate levels, suggesting that it may be limited by current photosynthesis.

Expression and function of the ST2 gene in a murine model of allergic airway inflammation.

BACKGROUND: We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear. OBJECTIVE: The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model. METHODS: We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2. RESULTS: Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-gamma, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone. CONCLUSION: These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases.

Presence of a genistein-responsive inhibitory mechanism on interleukin-1alpha-induced NF-kappaB activation.

Interleukin 1 (IL-1) is known to activate the signal transduction machinery, including the transcription factor, nuclear factor kappa B (NF-kappaB). The activation mechanism of NF-kappaB has been studied intensively, while the negative regulatory mechanisms of NF-kappaB remain to be clarified. In the present study, we found that genistein, a tyrosine kinase inhibitor, augmented IL-1alpha-dependent NF-kappaB activation, suggesting the presence of a tyrosine kinase mediating a suppression signal on NF-kappaB. As determined by luciferase reporter gene assay using kappaB-responsive element, genistein enhanced IL-1alpha-induced NF-kappaB activation. Although genistein failed to increase luciferase activity at 1 and 3 h after IL-1alpha stimulation, it induced prolonged activation beginning at 6 h after the initial stimulation. We next examined whether genistein augmented the DNA-binding activity of NF-kappaB, using electrophoretic mobility shift assay. In the case of the control experiment, the binding of NF- kappaB to the kappaB-responsive element peaked at 30 min after IL-1alpha stimulation, and decreased thereafter. In contrast, treatment with genistein maintained the maximum binding activity for at least 2 h after stimulation. Moreover, genistein enhanced the IL-1alpha-dependent degradation of IkappaBalpha. Taken together, our results indicate that genistein augments IkappaB degradation, resulting in continuous NF-kappaB activation. This suggests the possibility that tyrosine kinase negatively regulates NF-kappaB.

Helicobacter pylori seropositivity among 963 Japanese Brazilians according to sex, age, generation, and lifestyle factors.

Seropositivity of anti-Helicobacter pylori antibody (HP + ) was examined among Japanese Brazilians. The study was announced through 18 Japanese community culture associations in São Paulo, Curitiba, Mogi das Cruzes, and Mirandopolis in 2001. Among 969 participants, 963 individuals aged 33 - 69 years were analyzed. The overall HP + % was 48.1% (95% confidence interval, 44.9 - 51.3%). There was no difference in HP + % between 399 males and 564 females (49.6% and 47.0%, respectively). The HP + % increased with age; 35.3% for those aged 33 - 39 years, 46.2% for those aged 40 - 49 years, 46.5% for those aged 50 - 59 years, and 56.9% for those aged 60 - 69 years, but no differences were observed among the generations (Issei, Nisei, and Sansei) for each 10-year age group. Mogi das Cruzes, a rural area, showed a higher HP + %. Length of education was inversely associated with the positivity; the odds ratio (OR) relative to those with eight years or less of schooling was 0.61 (0.42 - 0.89) for those with 12 years or more. The associations with smoking and alcohol drinking were not significant. Fruit intake was associated with the HP + %; the OR relative to everyday intake was 1.38 (1.05 - 1.83) for less frequent intake, while intake frequencies of green tea, miso soup, and pickled vegetables (tsukemono) were not. Multivariate analysis including sex, 10-year age group, residence, education, and fruit intake showed that all factors except sex were significant. This is the largest study of HP infection among Japanese Brazilians, and the results indicated a similar pattern of age-specific infection rate to that for Japanese in Japan.

[Association between the interleukin 1B (C-31T) polymorphism and Helicobacter pylori infection in health checkup examinees].

PURPOSE: Associations between Helicobacter pylori (HP) infection and lifestyle factors have been demonstrated by several studies, but there are very few reports on links with host factors, especially concerning genetic polymorphisms for inhabitants of large city. The present investigation was conducted to determine the HP infection rate with reference to the Interleukin-1 beta gene (IL-1B) polymorphism and assess the interactions with smoking reported for outpatients. METHOD: The subjects were 468 participants in a health-check-up program of law of health for aged conducted by Nagoya Nishi Health Center. The participants were asked to permit use of their residual blood drawn during a health-check-up program and written informed consent was obtained for gene polymorphism tests. Data on smoking habit were obtained by self-administered questionnaire. The IL-1B C-to-T polymorphism at -31 was genotyped by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) and an anti-HP IgG antibody test was used for detecting HP infection. Differences in values were assessed by a chi 2 test. An unconditional logistic model was applied for estimating odds ratios with the computer program STATA Version 6. This study was approved by the Ethical Committee at Aichi Cancer Center in 2000 before it was commenced (Ethical Committee Approval Number 11-12) RESULTS: The HP infection rate was 52.6% (61/116) for the C/C genotype of IL-1B-31, 48.6% (89/183) for the C/T, and 63.2% (103/163) for T/T; the difference were not statistically significant. However, when non-current smokers were excluded, the rate were 47.8% (11/23), 52.9% (18/34), and 72.7% (16/22), respectively, indicating the T/T genotype to have a higher infection rate. The age-sex-smoking adjusted odds ratio (OR) relative to the C/C genotype were 0.97 (95% confidence interval, 0.59-1.57) for the T/C genotype and 1.73 (1.04-2.87) for the T/T genotype. Among current and former smokers the age-sex adjusted OR were 1.68 (0.50-5.71) for the T/C genotype and 5.29 (1.11-25.1) for the T/T genotype, suggesting a effect of this polymorphism prominent in smokers. CONCLUSION: An association between the IL-1B-31 polymorphism and persistent HP infection was observed for inhabitants with a smoking habit, indicating that this polymorphism is one genetic trait conferring an increased likelihood of persistent HP infection.

[Development of the chromatography analysis of liquid trapping 99mTc-Technegas using Jikei impinger].

We developed the equipment which collected 99mTc-Technegas into liquid (saline) and named this equipment an impinger of Jikei University Style. We further developed a technique using this impinger to evaluate its formation qualitatively by paper chromatography. Utilizing this technique we investigated various factors that caused environmental contamination by 99mTc-Technegas, including changes over time in a Technegas generator. It was demonstrated that upon getting mixed with oxygen gas to the argon gas, the Technegas generator induced contamination of 99mTc-Pertechnegas easily, leading to changes in its formation. The change of formation quality of the Technegas generator with the lapse of time was also revealed. These findings indicated that the maintenance and inspection of the equipment were important. This method is a simple and easy technique for the evaluation of 99mTc-Technegas formation, making it possible to perform the quality control of examination agent and the Technegas generator.