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Objective: In 1904, Hermann Wilbrand reported that nasal ON fibers form a loop into the contralateral ON, subsequently referred to as Wilbrand's knee. He had further theorized that a lesion affecting Wilbrand's knee would develop a distinct visual field defect characterized by an ipsilateral central scotoma with a contralateral superotemporal visual field defect. We present clinical evidence that disputes the existence of Wilbrand's knee., Methods: A retrospective analysis of 3 patients whose ONs were divided at the ON-chiasm junction is presented. Two patients had an ONS meningioma and the other patient had sarcoidosis of the ON. Resection of the lesion and the ON up to the nerve-chiasm junction was done to prevent the disease from extending into the OC and the contralateral ON. The patients had detailed neuro-ophthalmologic evaluations preoperatively and postoperatively., Results: After the resection of the ON at the ON-chiasm junction in the 3 patients, junctional scotoma could not be detected by visual perimetry., Conclusion: No clinical perimetric evidence was found to support the existence of Wilbrand's knee in the anterior visual pathway.

Allergic inflammation of the airways has a critical role in asthma development. We investigated a suppressive effect of verproside (3,4-dihydroxy catalpol) isolated from the extract of Pseudolysimachion longifolium on asthmatic parameters--such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness and mucus hypersecretion--in an OVA-sensitized/challenged mouse model. Verproside significantly inhibited the increase of total IgE and the cytokines IL-4 and IL-13 in plasma and bronchoalveolar lavage fluid, and also effectively suppressed airway hyperresponsiveness, eosinophilia and mucus hypersecretion in OVA-induced asthmatic mice. The efficacy of verproside was comparable to montelukast, an anti-asthmatic drug that is currently available. These results suggest that verproside could be a major marker in herbal medicines that are used for asthma treatment, and could also act as a lead for anti-asthmatic drugs.

The purpose of this study was to investigate the association between dietary patterns and sexual maturation among Korean children. A cross-sectional study was conducted in 422 boys and 365 girls aged 9-12 years living in Seoul, Korea. Three-day food records were obtained, and pubertal stages were determined with a questionnaire using Tanner stages. Body fat was measured by bioelectrical impedance analysis, and bone mass content at the right calcaneus was measured by portable dual-emission X-ray absorptiometry. Exploratory factor analysis with a Varimax rotation was applied to identify dietary patterns using twenty-four food groups. Four distinct dietary patterns--"rice and Kimchi", "shellfish and processed meat", "pizza and drinks" and "milk and cereal"--were obtained. Twenty-six per cent (24 % stage 2, 2 % stage 3) of boys had genital development, and 79 % (63 % stage 2, 16 % stage 3) of girls showed breast development. In boys, genital development was weakly positively associated with "shellfish and processed meat" dietary factor scores (odds ratio 1.65, CI 0.95, 2.89, P for trend 0.07) after adjusting for confounders. In girls, breast development was significantly positively associated with the factor score of "shellfish and processed meat" (odds ratio 1.88, CI 1.08, 3.26, P for trend 0.05). These results suggest that dietary patterns were related to body composition and sexual maturation among the Korean children. Further investigations are needed to identify components of the foods consumed in high amounts in these patterns and how they are related to sexual maturation.

Background: Postoperative onset of acute major depression in a patient with no previous history of psychiatric disorder is highly unexpected after skull base surgery., Case Description: A 38-year-old woman with no previous physical or mental illness presented with a 3-month history of left ear pain, short-term memory disturbance, and motor dysphasia. Magnetic resonance imaging revealed a large extraaxial tumor in the left middle fossa. Left temporal craniotomy was performed, achieving complete tumor resection. The patient showed signs of confusion, disorientation, and severe depression 3 days after the surgery. She developed insomnia and auditory hallucinations along with expressed suicidal ideation, then deteriorated rapidly, necessitating a transfer to a psychiatric unit. In spite of the intensive treatment with antidepressive and antipsychotic medications, she continued to have prolonged psychotic symptoms and depression for several months after surgery., Conclusion: Although the incidence is rare, psychiatric complications should be anticipated in patients undergoing resection of a large skull base tumor affecting the temporal lobe. The exact mechanism in this process is not clear; however, it is important to clinically differentiate treatable etiologies such as steroid-induced psychosis and postoperative delirium.

Beta amyloid (Abeta) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of Abeta is considered a primary therapeutic target. Immunization with Abeta can reduce Abeta burden and pathological features in transgenic AD model mice. Transgenic potato plants were made using genes encoding 5 tandem repeats of Abeta1-42 peptides with an ER retention signal. Amyloid precursor protein transgenic mice (Tg2576) fed with transgenic potato tubers with adjuvant showed a primary immune response and a partial reduction of Abeta burden in the brain. Thus, Abeta tandem repeats can be expressed in transgenic potato plants to form immunologically functional Abeta, and these potatoes has a potential to be used for the prevention and treatment of AD.

Objective: To quantify and compare the carotico-oculomotor triangle (COT) area before and after extradural anterior clinoidectomy (AC)., Methods: Ten cadaveric heads were dissected bilaterally. Before and after an extradural AC, the following points were measured: (1) the internal carotid artery (ICA) bifurcation to the tip of the anterior clinoid process (ACP) (A) and to the distal dural ring (A'), (2) the ICA bifurcation to the point where the oculomotor nerve becomes obscured by the tentorial fold (B) and to the porus oculomotoris after incision of the tentorial fold (B'), and (3) the tip of the ACP to the point where the oculomotor nerve becomes obscured by the tentorial incisura (C) and from the distal dural ring to the porus oculomotoris (C'). The area of the COT was calculated before and after AC (DeltaABC and DeltaA'B'C', respectively)., Results: The mean values were as follows: A: 9.15 +/- 0.93 mm, A': 13.45 +/- 0.82 mm; B: 7.80 +/- 1.24 mm, B': 9.90 +/- 1.21 mm; C: 7.15 +/- 0.99 mm, C': 9.3 +/- 1.26 mm; DeltaABC: 26.26 +/- 6.05 mm, DeltaA'B'C': 45.06 +/- 8.92 mm., Conclusions: Extradural AC enhances the exposure of the COT almost twofold. This increased exposure can be of significant help during resection of lesions of the parasellar and basilar apex regions.

Korea has experienced exceptionally rapid economic developments. Even though the country has managed to maintain aspects of its traditional diet, dietary habits are changing, especially among adolescents. This study was carried out to identify prevailing dietary patterns among Korean adolescents and to compare the nutrient intakes and dietary behaviours between the patterns. A 3 d diet record, collected from 671 Korean adolescents aged 12-14 years in Seoul, Korea, was assessed. By cluster analysis, subjects were classified into a modified (69.9 %) and a traditional (30.1 %) dietary pattern group. The modified group consumed more bread, noodles, cookies and pizza/hamburgers compared with the traditional group, which consumed mainly rice and kimchi (fermented cabbage). The modified group had significantly higher intakes of all nutrients. It had a higher total daily energy intake (7719 kJ), a higher daily energy intake from fat (29.8 %) and a higher cholesterol intake (326 mg/d), compared with the traditional group (6686 kJ, 24.8 % and 244 mg/d, respectively). The modified group was more likely to consume fast foods, fried foods and carbonated beverages even though they consumed more fresh fruits and milk, while the traditional group was more likely to have a rice-based diet and not to skip breakfast. These results suggest that monitoring dietary behaviours of adolescents, especially in a society experiencing a nutrition transition, is necessary in order to identify both negative and positive changes in respect of risk factors for nutrition-related chronic diseases as well as for undernutrition.

A new furofuran lignan, styraxlignolide B (1), and four new dibenzyl-gamma-butyrolactone lignans, styraxlignolides C-F (2-5), were isolated from the EtOAc-soluble fraction of stem bark of Styrax japonica. Known compounds, taraxerol (6), syringin (7), and (-)-pinoresinol glucoside (8), were also obtained. The structures of styraxligonolides B-F were determined as 2alpha-(4'-hydroxy-3'-methoxyphenyl)-6alpha-(3' ',4' '-methylenedioxyphenyl)-8-oxo-3,7-dioxabicyclo[3.3.0]octane 4'-O-(beta-D-glucopyranoside) (1), (2S,3S)-2alpha-(3' '-hydroxy-4' '-methoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4'-O-(beta-D-glucopyranoside) (2), (2S,3S)-2alpha-(4' '-hydroxy-3' '-methoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4'-O-(beta-D-glucopyranoside) (3), (2S,3S)-2alpha-(4' '-hydroxy-3' '-methoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4' '-O-(beta-D-glucopyranoside) (4), and (2S,3S)-2alpha-(3' ',4' '-dimethoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4'-O-(beta-D-glucopyranoside) (5) by spectroscopic means including 2D NMR. Compounds 1-8 were tested in vitro for antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Styraxlignolide C (2), styraxlignolide D (3), styraxlignolide E (4), and (-)-pinoresinol glucoside (8) exhibited weak radical-scavenging activity in the DPPH assay, with IC50 values of 380, 278, 194, and 260 microM, respectively.

Body weight, smoking, alcohol, physical activity, and diet have been proven to affect bone mineral density (BMD) directly or indirectly. Of these, body weight is perhaps best known to affect BMD. However, there is some debate as to whether lean body mass (LBM) or fat mass (FM), the two components of body weight, most determines BMD. Recently, newer peripheral densitometry devices have been developed, which have the advantages of low cost and portability, and this has made field epidemiologic study of osteoporosis possible. As the number of studies that have focused on the contribution made by body composition to BMD is limited, we investigated the relative contribution of LBM and FM to BMD in healthy Korean subjects. 402 age- and weight-matched subjects over 45 years old were selected from a population-based cohort. The mean ages of men and women were 64.1 +/- 8.7 (mean +/- SD) and 64.2 +/- 12.7 years, and mean weights were 63.0 +/- 8.2 and 63.1 +/- 8.2 kg, respectively. BMD was measured by peripheral dual-energy X-ray absorptiometry (DEXA) and body composition by bioelectrical impedance. Sociodemographic characteristics and physical activities were investigated using a standard questionnaire delivered by face-to-face interview. BMDs were 0.48 +/- 0.01 and 0.37 +/- 0.11 g/cm2 in men and women, respectively. In men, age, weight, body mass index (BMI), LBM, FM, physical activity, smoking, alcohol, and education were significantly correlated with BMD. In women, age, weight, BMI, LBM, FM, education, years since menopause, number of deliveries, and number of children breast-fed were significantly correlated with BMD. By multiple regression, LBM, education, smoking, and alcohol in men, and age, LBM, FM, smoking, and number of delivery in women were independent determinants of BMD. LBM was an important contributor for BMD in men, but both LBM and FM were equally important contributors in female to BMD. This stems from the fact that body composition changes with age differ in men and women. Thus, the augmentation of muscle mass in men and the maintenance of an optimal weight in women act to prevent osteoporosis.

Background: Adjustments in zinc losses and absorption are thought to maintain zinc homeostasis with changes in intake, but the capacity to make these adjustments appears to be affected by aging. Zinc status of the individual may also influence adjustments in fractional zinc absorption., Objective: The purpose of this study was to compare the effects of changes in zinc status due to zinc supplementation on fractional zinc absorption in young and elderly Korean women., Design: Zinc status and absorption were measured initially in 15 young (20-24 yr) and 15 elderly women (64-75 yr) confined to a metabolic unit and consuming a typical Korean diet. Upon discharge from the unit the women were supplemented with 22 mg zinc/d for 28 days. On d 20, the women returned to the unit for measurement of zinc status and absorption. Fractional zinc absorption (FZA) was estimated from the same typical Korean breakfast at both time points using the dual isotopic tracer method. Zinc stable isotopic ratios were measured in urine samples collected for 3 days following isotope administration., Results: Plasma and urinary zinc concentrations increased significantly with zinc supplementation in the young but not the elderly women. FZA decreased following zinc supplementation in the young women from 22 to 8% (p < 0.0001) and in the elderly women from 19 to 10% (p < 0.0001). The decline in young women was greater than that in elderly women (p < 0.05)., Conclusions: Both young and elderly women reduced their efficiency of zinc absorption with zinc supplementation. But, plasma and urinary zinc concentrations did not increase in the elderly following zinc supplementation suggesting that age altered the use of the additional zinc.

A bioassay for zinc status in humans has been sought due to the importance of zinc, an essential trace metal, for many divergent functions in the human body; however, a sensitive bioassay for zinc status in humans is lacking. To address this issue, we established gene expression profiles of human lymphoblastoid cells treated with 0 or 30 micro mol/L ZnSO(4) using microarray technology. A limited number of genes were responsive to 30 micro mol/L zinc based on the analysis of Affymetrix human genome U133A GeneChips. We also examined the gene expression patterns of zinc transporters in human lymphoblastoid cells using quantitative RT-PCR analysis. ZNT1 was upregulated in lymphoblastoid cells, whereas ZIP1 was downregulated in response to the increased zinc concentrations in the culture media. To evaluate the potential applications of using both zinc transporter genes as biomarkers of zinc status, we measured the expression levels of ZIP1 and ZNT1 in the peripheral leukocytes collected from 2 different age groups of Korean women. After administration of a zinc supplement (22 mg zinc gluconate/d for 27 d), ZIP1 expression decreased by 17% (P < 0.01) and 21% (P < 0.05) in the peripheral leukocytes collected from 15 young (20-25 y) and 10 elderly (64-75 y) subjects, respectively. ZNT1 expression was not affected by taking the zinc supplement. These data suggest a potential application of ZIP1 as a biomarker of zinc status in humans.

In an attempt to develop an edible vaccine, we transformed a recombinant hepatitis B virus (HBV) gene encoding the middle protein of HBV that contains the surface S and preS2 antigen into potato by Agrobacterium-mediated transformation. The HBV gene was under control of either the CaMV 35S promoter, the double 35S promoter with the AlMV 5' non-translated leader sequence, or the tuber-specific patatin promoter. HBV mRNA levels were higher with the 35S promoter than with the double 35S and patatin promoters; however, the levels of the S and preS2 antigen in the transformed tubers were higher with the patatin promoter than with the CaMV 35S and double promoters. The levels of preS2 antigen produced are the highest reported to date. Transgenic potato tubers were fed to mice, and the mice showed an immune response against the HBV S antigen.

A retrospective review of 53 consecutive patients who underwent a retrosigmoid vestibular nerve section (VNS) or microvascular decompression (MVD) through a modified suboccipital craniectomy with a minimum follow-up of 2 years was performed. Technical modifications to the suboccipital craniectomy included a skin incision designed to avoid the lesser and greater occipital nerves; a small, 2-cm diameter craniectomy with no intradural drilling of bone; and a simplified closure to prevent muscle adhesion to dura without the need for cranioplasty. The presence, duration, and severity of postoperative headache were the primary outcome measures. Craniectomy-related complications, operative time, and length of hospital stay were also reviewed. The incidence of postoperative headache after suboccipital craniectomy was 7.5% at 3 months (4/53), 3.8% at 1 year (2/53), and 3.8% at 2 years (2/53). Complications related to craniectomy included cerebrospinal fluid leakage (5.7%), aseptic meningitis (1.9%), and superficial wound infection (1.9%). The mean operative time was 145 and 98 minutes for VNS and MVD, respectively. The mean hospital stay was 2.2 and 3.6 days for VNS and MVD, respectively. Technical modifications of suboccipital craniectomy during retrosigmoid VNS and MVD lowered the incidence of postoperative headache and craniectomy-related complications and had no adverse effect on operative time or length of hospital stay.

Previously, we reported surgical results of the simplified retrosigmoid approach for vestibular nerve sectioning in the cases with intractable vertigo. Here, we introduce in details surgical procedures of the simplified retrosigmoid (also called "subasterional" here for simplification) approach developed by one of the authors (J.H.L.). This approach is to operate cerebello-pontine (C-P) angle lesions through a small upper lateral window below the transverse-sigmoid junction. The retroauricular 4-5 cm skin incision, triangular craniectomy 2 cm in width, dural opening and closure, special considerations, and reconstruction of the skull defect were outlined. The bony landmarks for triangle craniectomy below asterion were described in detail. The C-P angle was appropriately approached for microvascular decompression, removal of C-P angle tumors, and vestibular nerve resection. This subasterional approach was characterized by short operation time of 1-3 h and less postoperative discomforts compared to the conventional retrosigmoid approach.

Two new lactones, litsealactone A (1) and litsealactone B (2), were isolated from the leaves of Litsea japonica, together with three known lactones, hamabiwalactone A (3), hamabiwalactone B (4), and akolactone B (5). Hamabiwalactone B (4) and akolactone B (5) significantly inhibited complement activity in an in vitro anti-complement assay, with IC(50) values of 149 and 58 muM, respectively.

Four known flavonoids and two galloyl glucoses isolated from the stem-bark of Juglans mandshurica (Juglandaceae), namely taxifolin (1), afzelin (2), quercitrin (3), myricitrin (4), 1,2,6-trigalloylglucose (5), and 1,2,3,6-tetragalloylglucose (6), were evaluated for their anti-complement activity against complement system. Afzelin (2) and quercitrin (3) showed inhibitory activity against complement system with 50% inhibitory concentrations (IC(50)) values of 258 and 440 microM. 1,2,6-Trigalloylglucose (5) and 1,2,3,6-tetragalloylglucose (6) exhibited anti-complement activity with IC(50) values of 136 and 34 microM. In terms of the evaluation of the structure-activity relationship of 3,5,7-trihydroxyflavone, compounds 2, 3, and 4 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (4a) as their aglycones, and these were also tested for their anti-complement activity. Of the three aglycones, kaempferol (2a) exhibited weak anti-complement activity with an IC(50) value of 730 microM, while quercetin (3a) and myricetin (4a) were inactive in this assay system. Among the compounds tested, 1,2,3,6-tetragalloylglucose (6) showed the most potent anticomplement activity (IC(50), 34 microM).

Object: Clinoidal meningiomas remain a major neurosurgical challenge. Surgery-related outcome has been less than desirable in the past, and little attention has been directed toward improving visual deficits. The authors advocate a skull base technique for the removal of these difficult tumors and describe its advantages in terms of improving extent of resection and enhancing overall outcome, particularly visual function., Methods: A retrospective analysis was performed on data obtained in 26 consecutive patients with clinoidal meningiomas (including one patient with hemangiopericytoma) who underwent resection between June 1995 and January 2003. In 24 cases the skull base procedure involved extradural anterior clinoidectomy, optic canal unroofing, and optic sheath opening; in two cases a standard pterional craniotomy was performed. Fourteen of the 26 patients suffered significant preoperative visual deficits. All patients underwent thorough pre- and postoperative ophthalmological evaluations. The follow-up period ranged from 3 to 91 months (mean 42.3 months). Total resection was achieved in 20 patients (77%), and the majority (76.9%) of patients with preoperative visual impairment experienced significant improvement., Conclusions: With the use of the skull base technique, total resection and excellent visual outcome may be achieved with minimal morbidity in most patients with clinoidal meningiomas.

Four protostane-type triterpenes, alisol B 23-acetate (1a), alisol C 23-acetate (2a), alisol B (3a), and alisol A 24-acetate (4a), were isolated from the rhizome of Alismatis plantago-aquatice L. var. orientale Samuelson (Alismataceae) and eleven protostane derivatives (compounds 1-11) were obtained by selective modification from alisol B 23-acetate (1a). These compounds were investigated for their anti-complement activity against the classical pathway of the complement system. Alisol B (3a) and alisol A 24-acetate (4a) exhibited anti-complement activity with IC50 values of 150 and 130 microM. Among the synthetic derivatives, the tetrahydroxylated protostane triterpene (9) showed moderate inhibitory activity with IC50 value of 97.1 microM. Introduction of an aldehyde group at C-23 (10; IC50 value, 47.7 microM) showed the most potent inhibitory effect on the complement system in vitro.

We isolated the chalcone reductase (pl-chr) gene of Pueraria montana var. lobata by using a PCR strategy from cDNA pools of storage roots. A high level of expression of RNA was found in both stems and roots. The genomic Southern blot result suggests that pl-chr exists as a member of a small gene family. By introducing a pl-chr gene under the control of the 35S CaMV promoter into the pink-flowering Xanthi line of Nicotiana tabacum, the flower color was changed from pink to white-to-pink. The contents of anthocyanin in the flowers of the transgenic lines were dramatically decreased by 40%, but the total UV absorption compounds remained unchanged. The production of liquiritigenin in pl-chr overexpressed transgenic tobacco lines was confirmed by HPLC and MS analysis. The introduction of pl-chr gene provides a method to redirect the flavonoid pathway into 5'-deoxyflavonoid production in non-legume crops, in order to manipulate the phenylpropanoid pathway for isoflavonoid production.

Objective and Importance: Necrotizing sarcoid granuloma (NSG) has been recognized as a histological variant of sarcoidosis. Two cases of neurosarcoidosis (NS) with NSG with concomitant systemic disease have been described previously. We present an unusual case of primary NS-NSG that resembled an en plaque cranial base meningioma., Clinical Presentation: A 51-year-old man presented with a 3-month history of progressive left visual deterioration and proptosis. Brain magnetic resonance imaging demonstrated a large cranial base lesion occupying the left anterior clinoid process and sphenoid wing, extending to the left frontotemporal convexity. A second dura-based lesion was observed in the right parietal convexity. Both lesions enhanced homogeneously after administration of intravenous contrast medium. Magnetic resonance imaging characteristics were consistent with a typical clinoidal meningioma with an en plaque extension laterally., Intervention: A left frontotemporal craniotomy with extradural removal of the anterior clinoid process was performed. When the dura was opened, a red fibrous mass was identified. Intraoperative histological analysis revealed the presence of necrotizing and noncaseating granulomas. Postoperatively, cerebrospinal fluid, erythrocyte sedimentation rate, C-reactive protein, and serum and cerebrospinal fluid angiotensin-converting enzyme values were normal. The search for acid-fast bacilli or fungi was negative. A diagnosis of primary NS-NSG was made. The patient began long-term high-dose corticosteroid therapy. One and a half years after surgery, his vision had improved significantly and the lesions were stable as revealed by magnetic resonance imaging., Conclusion: The first case of primary NS-NSG in the absence of systemic sarcoidosis is reported. NS should be included in the differential diagnosis of dura-based lesions resembling meningioma.

Objective and Importance: Actinobacillus actinomycetemcomitans is a gram-negative coccobacillus that is known to cause a wide array of clinical infections in debilitated patients, including periodontal disease, soft tissue abscess, pleural empyema, endocarditis, cerebral abscess, and meningitis. We report a rare A. actinomycetemcomitans cavernous sinus abscess that caused painful ophthalmoplegia in a healthy man., Clinical Presentation: A 34-year-old man presented with a 3-month history of acute onset of left-sided retro-orbital pain that progressed to a complete left Cranial Nerve VI palsy and Cranial Nerve V1 and V2 hypesthesia. Magnetic resonance imaging revealed the presence of an enhancing lesion in the left cavernous sinus, which encased and narrowed the ipsilateral intracavernous segment of the internal carotid artery. Routine blood and cerebrospinal fluid analyses were normal. Tolosa-Hunt syndrome was suspected, and the patient was treated with high-dose corticosteroids. An open biopsy was performed after failed prolonged corticosteroid therapy., Intervention: A left frontotemporal craniotomy and cavernous sinus exploration through an interdural approach were performed. A soft reddish mass was found in the cavernous sinus around Cranial Nerve V1 and V2. Multiple biopsies were obtained. Pathological analysis revealed a purulent infection containing multiple gram-negative coccobacilli. The patient's pain improved immediately, and cranial neuropathy resolved during the next several weeks. After cultures demonstrated growth of A. actinomycetemcomitans, a regimen of orally administered amoxicillin and metronidazole was initiated. Eight months after surgery, the patient was free of symptoms and a repeat magnetic resonance imaging scan was normal., Conclusion: We present a rare bacterial abscess of the cavernous sinus causing painful ophthalmoplegia. In patients who present with presumed Tolosa-Hunt syndrome and do not improve with prolonged high-dose corticosteroid therapy, an open biopsy is recommended to exclude a bacterial infection.

The neurofibromatosis type2 (NF2) gene encodes an intracellular-associated protein that is referred to as either merlin or schwannomin. Merlin/Schwannomin is a tumor suppressor protein that has been reported to block the Ras-mediated cell proliferation and -anchorage-independent cell growth. However, its inhibitory mechanism is uncertain. In this report, merlin was demonstrated to be effective in suppressing Ras-induced foci-formation and its associated AP-1 activity in NIH3T3cells. In addition, merlin blocked Ras-induced Rb phosphorylation, and inhibited the increase of cyclin D1 levels. It also blocked E2F-1-dependent transcription. These results suggest that merlin inhibits abnormal cell proliferation which is activated via Ras by repressing Rb phosphorylation, blocking the increase of the cyclin D1 protein level, and inhibiting the activation of AP-1- and E2F-1-dependent transcription in NIH3T3 cells.

Two patients sought treatment for symptoms of bulbar motor dysfunction and the marked emotional lability that characterizes pseudobulbar palsy (PBP). Magnetic resonance (MR) imaging showed large petroclival masses with severe compression and displacement of the brainstem. A suboccipital craniectomy with a transpetrosal, transtentorial approach to the tumor was performed in both patients. One patient required a second-stage surgery to resect an extension of the tumor into the cavernous sinus. In both patients pathological evaluation confirmed the diagnosis of syncytial meningioma. After surgery, PBP resolved in both patients. Large posterior fossa tumors should be included in the differential diagnosis of patients with a clinical picture of bulbar motor dysfunction coupled with emotional lability.

Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate of the tree Boswellia serrata (frankincense). Because pentacyclic triterpenes have antiproliferative and cytotoxic effects against different tumor types, we investigated whether AKBA would act in a similar fashion on primary human meningioma cell cultures. Primary cell cultures were established from surgically removed meningioma specimens. The number of viable cells in the absence/presence of AKBA was determined by the non-radioactive cell proliferation assay. The activation status of the proliferative cell marker, extracellular signal-regulated kinase-1 and -2 (Erk-1 and Erk-2) was determined by immunoblotting with the antibody that recognizes the activated form of these proteins. Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2 - 8 microM. At low micromolar concentrations, AKBA rapidly and potently inhibited the phosphorylation of Erk-1/2 and impaired the motility of meningioma cells stimulated with platelet-derived growth factor BB. The cytotoxic action of AKBA on meningioma cells may be mediated, at least in part, by the inhibition of the Erk signal transduction pathway. Because of the central role the Erk pathway plays in signal transduction and tumorigenesis, further investigation into the potential clinical use for AKBA and related boswellic acids is warranted.

We report a rare skull base neurocytoma. A 44-year-old female with a history of focal seizure and progressive right-sided weakness sought treatment at an outside institution, where she underwent total resection of a "left medial sphenoid wing paraganglioma" in 1984. In 1995 after experiencing intense left-sided headaches for 3 weeks, the patient presented to our institution. Magnetic resonance imaging revealed a large local recurrence. She had deficits dating to her initial surgery, including moderate right-sided hemiparesis, complete left ophthalmoplegia, and left facial numbness.The patient underwent a craniotomy with extensive removal of the involved sphenoid bone and a subtotal resection of the tumor. Neurocytoma was diagnosed based on strong immunohistochemical staining for synaptophysin and no reactivity for glial fibrillary acidic protein. Postoperatively, her headaches resolved completely and her neurologic status remained at baseline. The residual tumor was treated with radiation therapy. After 5 years, she remains clinically and radiographically stable.Although typically located adjacent to the foramen of Monro, neurocytomas have now been reported in almost every subcompartment of the craniospinal axis. Finding neurocytomas in extraventricular locations may require revisiting the current theory that subependymal progenitor cells are the cells of origin for these tumors.

Purpose: To compare the outcome of salvage radiotherapy (RT) and surgery for recurrent head-and-neck chemodectomas., Materials and Methods: We retrospectively studied 70 patients with benign chemodectomas of the head and neck treated with surgery at the Cleveland Clinic between July 1969 and August 1999; 29 of these patients were diagnosed with recurrent tumors. Salvage RT was used in 12 patients (gamma knife radiosurgery for 7, conventional external beam RT for 4, and intensity-modulated RT for 1 patient). The median follow-up was 55 months for the entire group of 70 patients., Results: The median time to recurrence was 36 months. Of the recurrences, 16 were glomus jugulare, 7 were carotid body tumors, 5 were glomus tympanicum, and 1 was thyroid paraganglioma. RT was used in 12 patients (9 patients with glomus jugulare, 2 with glomus tympanicum, and 1 with thyroid paraganglioma). Surgery was performed in 17 patients (7 patients with glomus jugulare, 7 with carotid body, and 3 with glomus tympanicum). For patients with glomus jugulare and glomus tympanicum tumors, the 5-year freedom from disease progression was 100% for patients treated with RT vs. 62% for those treated with surgery (p = 0.0124). Seven patients with carotid body tumors and 1 patient with thyroid paraganglioma were treated successfully with surgery and RT, respectively. No significant side effects were associated with RT; however, postoperative complications occurred in 8 of the 17 surgery patients (new cranial nerve palsies, meningitis, infection, and cerebrospinal fluid leak)., Conclusion: Salvage RT appears superior to surgery and should be considered the treatment of choice for patients with recurrent glomus jugulare and glomus tympanicum tumors. For recurrent carotid body tumors, surgery produced excellent local control, most likely because of the easier resectability in this location.

Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from the gum resin exudate from the stem of the tree Boswellia serrata (frankincense). AKBA has been recently identified as a novel, orally active, non-redox and non-competitive 5-lipoxygenase inhibitor that also inhibits topisomerase I and II in vitro. Because natural pentacyclic triterpenes have an antiproliferative effect against different tumor types, we investigated the effects of AKBA on the proliferation of 11 primary cell cultures established from human surgical specimens of meningiomas, common central nervous system tumors. Treatment of meningioma cells by AKBA revealed a potent cytotoxic activity with half-maximal inhibitory concentrations in the range of 2-8 microM. At similar, physiologically achievable concentrations, AKBA rapidly (within minutes) and potently inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk-1 and Erk-2) in meningioma cells stimulated with platelet-derived growth factor BB. High expression level of 5-LO was detected in primary meningioma cells and surgical specimens by immunoblotting analysis, suggesting the possible role of 5-LO in meningioma tumorigenesis. Considering the critical importance of the Erk-1/2 signal transduction pathway not only in meningiomas but in other human neoplasms, the interruption of signaling through this evolutionarily conserved pathway might be one of the mechanisms by which AKBA induces suppression of proliferation and apoptosis of different tumor types.

Objective: To determine the surgical efficacy of a simplified retrosigmoid approach for vestibular nerve sectioning., Study Design: A retrospective analysis., Setting: Tertiary academic referral center., Patients: Twenty-eight consecutive patients who underwent vestibular nerve sectioning for intractable peripheral vestibular disorders., Intervention: All patients had a simplified retrosigmoid approach for vestibular nerve sectioning., Main Outcome Measures: Functional outcome after vestibular nerve sectioning was analyzed with respect to improvement in patient disability from vertigo and reduction in the frequency of definitive vertigo attacks. Resolution of lightheadedness provided an additional outcome measure. The incidence of surgical complications, including postoperative headache, was determined, and the operative time was reviewed., Results: Twenty-six patients (92.9%) had an improved functional level postoperatively, 21 (75.0%) had excellent improvement, 4 (14.3%) had significant improvement, 1 (3.6%) had limited improvement, and 2 (7.1%) had no change. No patient was worse postoperatively. Eighteen of 23 Ménière's patients (78.3%) had complete control of definitive vertigo attacks after vestibular nerve sectioning. Improvement in lightheadedness was seen in 23 patients (82.1%), 11 (39.3%) of whom reported complete resolution. Postoperative headache developed in 1 (3.6%) patient. No patients experienced infection, facial weakness, or leakage of cerebrospinal fluid. Mild hearing deterioration was seen in 2 patients (7.1%). The mean operative time was 76.3 minutes., Conclusion: With excellent efficacy, short operative time, and a low incidence of postoperative hearing loss or headache, this simplified retrosigmoid technique should be considered for vestibular nerve sectioning in patients with intractable peripheral vestibular disorders.

The present study focused on whether serum extracellular superoxide dimutase (EC-SOD) activity can be used as a functional indicator of marginal zinc deficiency in humans. Subjects in this study were 444 healthy adults over 30 yr of age living a normal rural life in Kyunggi province, Korea. The mean dietary zinc intake of subjects obtained from one 24-h recall was 6.41 +/- 4.35 mg and the average serum zinc concentration of the subjects was 11.06 +/- 2.44 micromol/L. Subjects were divided into three groups by serum zinc concentrations: adequate (serum zinc >10.7 micromol/L), low (serum zinc 9.0-10.7 micromol/L), and very low (serum zinc <9.0 micromol/L) groups. A total of 50 subjects were selected from the three groups for analysis of EC-SOD activities. The EC-SOD activity of subjects increased with increasing serum zinc concentrations, and the activities of the three groups were significantly different as indicated by the Kruskal-Wallis test (p = 0.0239). Also, serum EC-SOD activities were significantly correlated with serum zinc concentrations (r = 0.289, p = 0.04). Serum EC-SOD activities, however, were not significantly correlated to the dietary zinc intakes. In conclusion, these results show that EC-SOD activities are decreased in subjects with low serum zinc concentrations and suggest that EC-SOD activity may be a functional indicator of zinc nutritional status in humans.

Objective: This study determined which, if any, of the three superoxide dismutase (SOD) enzyme activities were detectable in BAL fluid (BALF)., Background: The identity and concentrations of antioxidant molecules in BALF have not been fully characterized. One important class of antioxidants is that of the SOD enzymes., Methods: BALF from control nonsmokers (n=9), smokers (n=7), and asthmatic subjects (n=12) were examined for SOD activity by a modified pyrogallol auto-oxidation method. The particular SOD enzyme or enzymes responsible for any activity were identified based on activity inhibition data and gel filtration column chromatography patterns., Results: SOD activity was detected in all samples. Unlike serum or some other fluids, in which the enzyme extracellular SOD accounts for virtually all SOD activity, the enzyme SOD 1 accounted for virtually all SOD activity. BALF SOD activities were lower for smokers than for control or asthmatic subjects (p<0.05)., Conclusion: BALF SOD 1 activities can be measured as part of lung antioxidant studies. Data from a limited number of subjects suggested that smokers can have low BALF SOD values.

We have isolated a chalcone synthase gene 2 (ST-CHS2) from potato by rapid amplification of cDNA ends by PCR. CHS2 cDNA had high homology to tomato LET-CHS2 (98%), petunia PHCHSJ (94%), potato ST-CHS1B (92%), petunia PHCHSA (92%), and LET-CHS1 (90%) at the overall 389-amino acid level. Genomic hybridization analysis indicated that CHS genes of potato comprise a family of at least six individual members.

Objective: Suspicions that mild zinc deficiency is common among the elderly cannot be confirmed or refuted because definitive indicators of zinc status are lacking. The goal of this study was to document the clinical responsiveness of parameters of zinc status in a group of older adults consuming a carefully controlled diet: first moderately low in zinc (3.97 mg/day for 15 days) and then high in zinc (28.19 mg/day for 6 days)., Methods: Fifteen older adults (mean age = 66.6 yrs) volunteered to consume a marginally zinc-deficient diet for 15 days followed by 6 days of zinc repletion. Plasma concentrations of erythrocyte metallothionein and the enzyme 5'-nucleotidase, as well as levels of zinc, alkaline phosphatase, copper and ceruloplasmin were measured before and after zinc depletion and repletion., Results: Plasma zinc levels were not altered during the study. Alkaline phosphatase (AP) values did not change in the expected direction, although a small decrease in AP following zinc repletion was statistically significant. Erythrocyte metallothionein results followed a pattern similar to that of alkaline phosphatase, little change, but a small, statistically significant drop after zinc repletion. As expected, there were no diet-associated changes in plasma copper and ceruloplasmin levels. In contrast, plasma concentrations of the enzyme 5'-nucleotidase decreased (p < 0.01) from 2.7 +/- 0.5 to 1.1 +/- 0.5 U during zinc depletion and increased (p < 0.05) to 2.2 +/- 0.4 U after 6 days of repletion., Conclusions: Mild zinc deficiency is difficult to detect. In this study, traditional indicators such as plasma zinc and alkaline phosphatase did not change as would be expected in response to alterations in zinc intake. Likewise, erythrocyte metallothionein did not respond to altered zinc intakes as expected but this factor may reflect long-standing or more severe zinc depletion and thus requires additional study. Activity of the enzyme 5'-nucleotidase appears responsive to acute changes in zinc intake; however, more work is needed to define how well these activities will reflect zinc intake in other types of subjects.