Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

CRISPR-Cas9 and beyond: identifying target genes for developing disease-resistant plants.

Throughout the history of crop domestication, desirable traits have been selected in agricultural products. However, such selection often leads to crops and vegetables with weaker vitality and viability than their wild ancestors when exposed to adverse environmental conditions. Considering the increasing human population and climate change challenges, it is crucial to enhance crop quality and quantity. Accordingly, the identification and utilization of diverse genetic resources are imperative for developing disease-resistant plants that can withstand unexpected epidemics of plant diseases. In this review, we provide a brief overview of recent progress in genome-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) technologies. In particular, we classify disease-resistant mutants of Arabidopsis thaliana and several crop plants based on the roles or functions of the mutated genes in plant immunity and suggest potential target genes for molecular breeding of genome-edited disease-resistant plants. Genome-editing technologies are resilient tools for sustainable development and promising solutions for coping with climate change and population increases.

Prevalence of Antiphospholipid Antibody Positivity and Association of Pretransplant Lupus Anticoagulant Positivity With Early Allograft Dysfunction in Liver Transplantation.

BACKGROUND: Antiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). METHODS: Data of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: The prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-ß2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P < .001). Model for End-stage Liver Disease score, operation time, and C-reactive protein level remained significant after multivariable analysis. CONCLUSION: A positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

Determining the Cut-off Values for Sarcopenia in the Korean Elderly Population Using Bioimpedance Analysis.

BACKGROUND: Bioimpedance analysis (BIA) is known to be a useful method for assessing sarcopenia because cost-effective and not involving radiation exposure. However, the cut-off values for sarcopenia using BIA have not yet been determined in the Korean population. OBJECTIVES: To establish the cut-off values for sarcopenia in the Korean elderly population with the use of BIA. METHODS: Body composition assessed by BIA was obtained in 7,641 participants aged 20-34 years and 3,902 participants aged ≥65 years from data routinely collected during health examinations at Seoul National University Gangnam Center. Appendicular skeletal muscle mass was adjusted for height and weight. Gender-specific cut-points for class I and class II sarcopenia were defined as 1 and 2 standard deviations below the mean in the reference group aged 20-34 years, respectively. In addition, the gender-specific, lowest 20th percentile cut-offs for muscle mass in participants aged ≥65 years were determined. RESULTS: The cut-offs for class I and class II sarcopenia in men for height-adjusted appendicular skeletal mass were 6.74 kg/m2 and 5.96 kg/m2 and for weight-adjusted appendicular skeletal mass were 29.4% and 27.4%, respectively; those in women for height-adjusted appendicular skeletal mass were 4.93 kg/m2 and 4.35 kg/m2, and for weight-adjusted appendicular skeletal mass were 25.6% and 23.9%, respectively. The lowest 20th percentile cut-offs for height-adjusted and weight-adjusted appendicular skeletal mass were 6.69 kg/m2 and 28.9% in men, and 5.76 kg/m2 and 24.5% in women, respectively. Based on the derived cut-offs, prevalence of class II sarcopenia in participants ≥65 years of age for height-adjusted and weight-adjusted appendicular skeletal mass was 3.7% and 3.5% in men, and 0.2% and 11.2% in women, respectively. Among the above-mentioned definitions, sarcopenia by height-adjusted appendicular skeletal mass was significantly associated with 2-year mortality in older participants. CONCLUSIONS: Muscle mass deficit in the Korean population can be assessed based on the cut-offs determined in this study using BIA.

Exclusive radiotherapy for gliomatosis cerebri: long-term follow-up at a single institution.

PURPOSE: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri. METHODS: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191). RESULTS: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively). CONCLUSIONS: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival.

A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis.

Factors affecting growth and final adult height after pediatric renal transplantation.

BACKGROUND: Growth retardation is a common problem for children with chronic kidney disease. Although renal transplantation (RTx) resolves endocrine metabolic and uremic disturbances, growth continues to be suboptimal. This study aims to describe changes in height from diagnosis to final adult height (FAH) in Korean renal allograft recipients and determine factors associated with posttransplantation growth. METHODS: We retrospectively reviewed 63 renal allograft recipients who underwent RTx at <15 years of age with regular follow-up for >3 years afterwards. Pre- and post-RTx growth was analyzed by height Z scores (Ht_Z) at RTx, 2 and 5 years follow-up, and at FAH. RESULTS: Ht_Z decreased from diagnosis to dialysis by -0.8 (P = .009) and from dialysis to RTx by -0.46 (P < .001). The mean baseline Ht_Z at RTx was -1.62 ± 1.36. The change in Ht_Z at 2 and 5 years after transplantation was 0.68 ± 0.88 and 0.48 ± 0.86, respectively. Both variables were negatively correlated with baseline age at RTx. Mean FAH was -1.22 ± 1.11 and was positively correlated with baseline height at RTx. Height at start of dialysis and dialysis duration were significant determinants of baseline height at RTx (P < .001). CONCLUSIONS: Although there is significant posttransplant catch-up growth among younger recipients and among those with greater baseline height deficit, catch-up growth is not sustained and greater FAH is attained in those who are taller at RTx. Achieving greater height before dialysis and decreasing dialysis duration leads to maximal height at RTx as well as greater FAH.

Combination treatment with corticosteroid, cyclosporine A, and mycophenolate in refractory nephrotic syndrome.

BACKGROUND/AIMS: Refractory nephrotic syndrome (NS) is problematic because the optimal therapy for this disease is unclear and because persistent NS progresses eventually to end-stage renal disease. We report our experience using a combination of corticosteroid, cyclosporine A (CsA), and mycophenolate mofetil (MMF) to treat 10 refractory NS patients. METHODS: Ten refractory NS patients, who showed resistance to corticosteroid and CsA, were treated with triple immunosuppressive therapy. Cyclophosphamide and MMF had been used previously in 6 patients, but had failed to induce remission. RESULTS: Triple immunosuppressive therapy was discontinued after 4 months in 1 patient because of progressive azotemia. Partial remission was achieved in 9 of the 10 patients after 10 months, and remission was maintained during the treatment (urine protein to creatinine ratio, mg/mg, baseline vs. 12th month; 5.7 ± 1.8 vs. 1.4 ± 0.7). Renal function was preserved in these 9 patients (estimated GFR, ml/min/1.73 m2, baseline vs. 12th month; 71.4 ± 29.1 vs. 68.9 ± 31.5). Of the 7 patients who discontinued triple immunosuppressive therapy, remission and renal function were maintained in 4 patients. CONCLUSION: Triple immunosuppressive therapy significantly reduced proteinuria and preserved renal function in refractory NS patients, indicating a promising role of this therapy for refractory NS.

Relationship between radiological characteristics and combined 1p and 19q deletion in World Health Organization grade III oligodendroglial tumours.

OBJECTIVE: The radiological characteristics of World Health Organization grade III oligodendroglial tumours in relation to chromosome 1p and 19q deletions were analysed. METHODS: 56 patients recently diagnosed with anaplastic oligodendroglioma (AO, n=49) or anaplastic oligoastrocytoma (AOA, n=7) were studied. Their preoperative magnetic resonance images were examined. Deletions of chromosome 1p and 19q were determined using the fluorescence in situ hybridisation method. Both 1p and 19q chromosomes had deletions (1p19q codeletion) in 39 patients (36 AO and 3 AOA). RESULTS: Tumors associated with the 1p19q codeletion were predominantly located in the frontal lobe (p=0.044). The magnetic resonance image characteristics of indistinct tumour borders (p=0.005 on T1, p=0.036 on T2) and a heterogeneous intratumoural signal intensity (p=0.033 on T1, p=0.041 on T2) were significantly correlated with the 1p19q codeletion. Analysis of patient survival showed those with the 1p19q-co-deleted tumours survived significantly longer than those lacking the 1p19q codeletion (p=0.042). The presence of a heterogeneous signal intensity in T2-weighted images, a characteristic significantly related to the 1p19q codeletion, indicated a favourable prognosis for patients' survival (HR; 0.125, 95% CI, 0.016 to 0.963, p=0.046) based on multivariate analysis. CONCLUSION: A relationship between radiological characteristics and molecular signatures in AO/AOAs was shown. It is believed that radiological characteristics have prognostic value as a surrogate marker for molecular characteristics.

Genetic immunotherapy of lung cancer using conditionally replicating adenovirus and adenovirus-interferon-beta.

Genetic immunotherapy is considered an ideal treatment modality for cancer because of its systemic nature. This study was designed to develop a potent novel genetic immunotherapy by combining conditionally replicating adenovirus (CRAd) and replication-defective adenovirus expressing interferon-beta (ad-IFN-beta). We investigated the efficacy of this therapy in an immunocompetent mouse tumor model. Transduction with CRAd (Delta24RGD) induced cytolysis in a mouse lung cancer cell line (Lewis lung carcinoma (LLC)). Combined transduction of ad-IFN-beta and Delta24RGD in the LLC cells induced a greater and more prolonged production of IFN-beta. Media transfer from the LLC-Delta24RGD-ad-IFN-beta to untransduced LLC cells induced the production of IFN-beta; these results confirmed the replication and release of ad-IFN-beta. LLC cells transduced with ad-IFN-beta and Delta24RGD had decreased tumorigenicity in syngeneic mice. Tumor vaccination with irradiated LLC-ad-IFN-beta-Delta24RGD showed a significant increase in the survival of tumor-bearing syngeneic mice compared with mice with a single transduced LLC vaccination; this was mediated by an enhanced cytotoxic T-lymphocyte response against the LLC cells. The results of this study showed that cotransduced Delta24RGD to ad-IFN-beta aided the replication of ad-IFN-beta in the LLC cells. A high local concentration of IFN-beta and local release of tumor antigen by CRAd induced strong antitumor immunity. This combination strategy might provide a powerful means by which ad-cytokines and CRAd can be combined and other adenoviruses expressing different cytokines might also be used.

Evaluation of tumour response after gamma knife radiosurgery for residual vestibular schwannomas based on MRI morphological features.

OBJECTIVE: To evaluate tumour response after gamma knife (GK) radiosurgery for residual vestibular schwannoma (VS) based on MRI morphological features. METHODS: Sixty-one patients with histopathologically confirmed VS underwent GK radiosurgery with marginal tumour doses of 9.0-14.0 Gy (mean, 12.5). Mean tumour volume at GK radiosurgery was 3.65 ml (range, 0.52-15.50). GK radiosurgery was performed 0.3-95.7 months (median, 5.8) after microsurgery. Tumour volumes and half-reduction time were calculated using serial MRI. The morphological features of VS were documented by pre-microsurgical MRI. Histopathological investigation included Antoni-type dominance, the proliferation marker Ki-67 and tumour vascularity. RESULTS: Median duration of radiological follow-up was 53.7 months (range, 24.1-102.2) and the 8-year actuarial tumour control rate was 93.5%. No factor was associated with tumour control, although a cystic VS had borderline significance (p = 0.089). Mean tumour half-reduction time was 8.70 years (range, 0.57-79.89) and tumour half-reduction time in cystic VS proved to be significantly shorter than those in solid VS (p = 0.006). Thrombotic vessels (p = 0.015) and abnormal vessel proliferation (p = 0.003) were significantly more prominent in cystic VS than those in solid VS. CONCLUSIONS: GK radiosurgery appeared to be an effective treatment modality for residual tumour control after microsurgery. Owing to having relatively abundant tumour vascularity, residual solid portions of cystic VS resulted in efficient shrinkage after GK radiosurgery. Therefore, GK radiosurgery was found to be a rewarding therapeutic approach to the residual solid portions of cystic VS.

Atypical and anaplastic meningiomas: prognostic implications of clinicopathological features.

OBJECTIVES: To evaluate patient outcome and investigate the prognostic factors of high-grade meningiomas by adopting the 2000 World Health Organization (WHO) classification system. METHODS: Between 1986 and 2004, 74 patients were diagnosed with high-grade meningioma: 33 with atypical and 41 with anaplastic meningioma. The mean follow-up was 58.5 months. We reclassified all surgical specimens, according to the 2000 WHO classification system, using two expert neuropathologists. RESULTS: Forty of 74 meningiomas were reclassified as atypical meningioma and 24 as anaplastic meningioma. Overall and recurrence-free survivals were significantly longer in patients with atypical than in those with anaplastic meningioma: 142.5 versus 39.8 months and 138.5 versus 32.2 months, respectively (p<0.001). In patients with atypical meningiomas, brain invasion and adjuvant radiotherapy were not associated with survival; however, in the brain invasion subgroup, adjuvant radiotherapy improved patients' survival. In patients with anaplastic meningioma, the prognostic factors were brain invasion, adjuvant radiotherapy, malignant progression, p53 overexpression and extent of resection. The p53 overexpression was the only factor associated with malignant progression (p = 0.009). CONCLUSIONS: The 2000 WHO classification has identified the truly aggressive meningiomas better than did the previous criteria. A precise meningioma grading system may help to avoid over-treatment of patients with an atypical meningioma as, once the tumour has "declared itself" by recurrence and histological features, it becomes a tumour that is poorly amenable to current therapies.

Microcystic meningiomas: radiological characteristics of 16 cases.

BACKGROUND: As a rare subtype of meningioma, only a few reports deal with radiological characteristics of microcystic meningiomas and the problem remains controversial. The authors have analyzed the radiological findings of a series of microcystic meningiomas with a special focus on magnetic resonance images (MRI) and conventional angiography. METHOD: Sixteen patients of histologically proven microcystic meningiomas were included. Analysis of preoperative MRI including signal intensity characteristics, enhancement patterns and peritumoural edema were performed and correlated with angiographic and histological findings. Peritumoural edema was graded using edema index (EI) which was defined as the ratio of VE/VT. FINDINGS: The tumours were uniformly visualized as a high-signal mass lesion in T2-weighted images and as a low-signal mass lesion in T1-weighted images regardless of tumour vascularity shown by angiography. T2-weighted images revealed that peritumoural brain edema was severe in 11, moderate in 1, mild in 2 and negligible in 2 patients and this was closely related to the co-existence of irregular tumour marginal enhancement. However, other features failed to distinguish these lesions from other subtypes of meningioma. CONCLUSIONS: The cases presented demonstrate that characteristic MRI findings suggestive of microcystic meningiomas are; (1) low signal intensity mass in T1- and high signal intensity mass in T2-weighted images; (2) high incidence of peritumoural edema.

The significance of gemistocytes in astrocytoma.

BACKGROUND: A retrospective clinical analysis of astrocytomas which contained a significant proportion of gemistocytes was carried out in order to evaluate their effect on prognosis, and other factors influencing prognosis. METHOD: From 253 consecutive cases of astrocytic tumours in adults, 25 were selected who had more than 20% gemistocytes in every high-power field examined. 9 of these had anaplasia, the remainder did not. They were divided into two groups according to the proportion of gemistocytes; group A, contained more than 60% gemistocytes, and group B, had between 20 and 60% gemistocytes. TUNEL and immunohistochemical staining for PCNA, p53, Ki-67, bcl-2 were performed in the 20 available cases. FINDINGS: The median follow-up period was 46 months. There were 14 recurrences, with a median time to recurrence of 15 months. Thirteen repeat operations were performed in nine cases, and two cases showed recurring malignant transformation. The overall median survival time following diagnosis was 73 months and the 5-year survival rate was 52%. There were no significant differences in median survival between groups A and B with different proportions of gemistocytes. On the other hand the median survival of the gemistocytic astrocytomas with anaplasia was 25 months, compared with 158 months for those without anaplasia (p=0.0005). The significant impact of anaplasia on survival persisted in both groups. There were no significant differences in immunohistochemical staining between the two groups, with the exception of staining for Ki-67 (means of the two groups: group A 1.40; group B 2.50). CONCLUSIONS: It is suggested that the proportion of gemistocytes does not itself affect prognosis.

Stereotactic biopsy for intracranial lesions: reliability and its impact on the planning of treatment.

BACKGROUND: The authors present a retrospective analysis of 308 computed tomography (CT)-guided stereotactic biopsies in 300 patients in order to evaluate the reliability and efficacy of the stereotactic biopsy for intracranial lesions. METHOD: All patients were suffering from undetermined intracranial lesions and treated at Seoul National University Hospital between January 1993 and December 1999. Age ranged from three to 79 years (mean 41); the male to female ratio was 180:120. All patients underwent CT-guided stereotactic biopsy for the histological verification and/or evacuation of the cyst using Riechert-Mundinger stereotactic system. FINDINGS: Histological diagnosis was made in 275 patients (diagnostic yield 91.7%). Diagnostic yield was better in group with frozen section examination during the stereotactic procedure than the group without it (p=0.01). Neoplastic lesions were more likely to be diagnosed in stereotactic biopsy than non-neoplastic lesions (p=0.02). Among 30 patients who underwent craniotomy after the stereotactic biopsy, the histological diagnoses after the craniotomy were identical to those of the stereotactic biopsy in 29 patients (diagnostic accuracy 96.7%). Two patients died within seven days after the stereotactic biopsy (mortality 0.6%). The postoperative new neurological deficit or aggravation of the neurological status was found in 19 patients, including transient cases of seven patients (permanent morbidity rate 3.9%). Histologically malignant gliomas and deeply-located lesions were the significant risk factors for the development of complications. In 148 cases, histological diagnosis of the stereotactic biopsy was different from the preoperative clinical diagnosis. Among these cases, the treatment plan was changed after stereotactic biopsy in 81 cases. CONCLUSIONS: Stereotactic biopsy for intracranial lesions is a reliable and relatively safe procedure. It is also a very efficacious method especially in patients who need histological confirmation for the treatment.

Characterization of Tobacco mosaic virus Isolated from Potato Showing Yellow Leaf Mosaic and Stunting Symptoms in Korea.

Four isolates of Tobacco mosaic virus (TMV-potato 1 to 4) were obtained from potato plants (Solanum tuberosum) in cultivated potato plantings in Korea. These isolates were differentiated based on biological properties, symptomatology, and nucleotide sequence analysis of the coat protein (CP) gene. TMV potato isolates caused typical symptoms on 20 inoculated plant species as compared to the type (U1) TMV strain. The four isolates each produced distinctly different symptoms on Gomphrena globosa. In contrast to the type strain of TMV, infections with two of the isolates reported here were not restricted to inoculated leaves of G. globosa but moved systemically through the plants. In addition, three additional systemic hosts (Chenopodium amaranticolor, C. quinoa, and C. murale) for TMV were revealed. Sequence analysis of the CP gene differentiated TMV-potato isolates. The CP gene sequence exhibited significant identity (83.1 to 99.2%) among TMV-potato isolates while showing 88.1 to 99.4% identities on predicted amino acid sequences. Based on a comparison of the CP gene nucleotide and deduced amino acid sequences between TMV-potato isolates and other TMV strains, TMV-potato 1, 3, and 4 were closely related to TMV strains U1, U2, V-FAVA, and NC82 with 98.8 to 100% identity. In contrast, TMV-potato 2 was closely related to TMV strains L, KP, KO-TOB, K1, and K2 with 93.8 to 98.8% identity.

Biological behavior and tumorigenesis of subependymal giant cell astrocytomas.

In spite of the benign nature of subependymal giant cell astrocytomas (SEGAs), some show massive hemorrhage, rapid growth, and tumor recurrence. This led us to investigate the biological behavior, cell dynamics, and tumorigenesis of SEGAs. All patients (4 men and 3 women; age range, 6-27 years; mean, 13.6 years) had features of tuberous sclerosis complex and obstructive hydrocephalus. One patient had intratumoral bleeding. In two patients, sequential neuroimaging showed a subependymal nodule growing to become a SEGA. All underwent surgical resection without radiation therapy. One tumor recurred and was treated surgically. There were no postoperative deaths. The presence of cytologic atypia, mitoses and vascular proliferation had no implication in terms of the clinical course. MIB-1 labeling indices were low (mean, 0.9), indicating low proliferative potential. Unexpectedly, bcl-2 staining was sparse and bax staining predominated in majority of cases. However, the mean value of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling index was low. Immunohistochemically, tumors were positive for both glial and neuronal markers. In the majority of our cases, the expression of p53 was low. Only one tumor was focally positive for tuberin. SEGAs have low proliferative potential and apoptotic activity, and exhibit features of mixed glial-neuronal differentiation. In contrast to p53, tuberin is suggested to be the tumor suppressor in this tumor.

Postoperative spinal seeding of craniopharyngioma. Case report.

The authors present a case of postoperative spinal seeding of papillary craniopharyngioma. This 27-year-old man who had previously undergone subtotal removal of a suprasellar craniopharyngioma was admitted because of low-back and right leg pain. Results of neurological examination showed a limitation in straight-leg raising in the right side with no sensorimotor changes. Magnetic resonance imaging of the lumbar spine demonstrated multiple enhanced intradural extramedullary masses causing spinal cord compression. Pathological examination of the tumor tissue obtained via laminectomy revealed papillary craniopharyngioma, which had the same histological features as those of the previous suprasellar tumor. Several ectopic recurrences of craniopharyngioma have been reported; however, the authors believe that this is the first published report of the spinal seeding of craniopharyngioma.

Prevalence of Gs alpha mutations in Korean patients with pituitary adenomas.

The reported frequencies of Gs alpha mutations (gsp mutations) in growth hormone (GH)-secreting pituitary adenomas are variable (ranging from 4.4 to 43%), and the presence of these mutations in the other pituitary adenomas is still a matter of controversy. Previous clinical and biochemical analyses of patients with GH-secreting pituitary adenomas and gsp mutations produced conflicting results and did not demonstrate obvious characteristics. Therefore, we investigated the prevalence of gsp mutations in Korean patients with pituitary adenomas and elucidated the characteristics of these patients. Forty-four GH-secreting adenomas, 7 prolactin (PRL)-secreting adenomas and 32 clinically non-functioning adenomas were examined for the presence of point mutations in codon 201 and 227 of the Gs alpha gene using a nested PCR and direct sequencing of DNA extracted from fresh tissue or paraffin-embedded pituitary adenoma samples. Seven of the 44 GH-secreting pituitary adenomas had point mutations at codon 201 or 227; of these, five mutations were in codon 201 and two were in codon 227. In patients with gsp mutations, mean tumor size was significantly smaller than in patients without gsp mutations (15.9+/-8.7 mm vs. 24.9+/-14.9 mm, P<0.05). Age, sex, basal GH levels, GH response to oral glucose loading, GH response to octreotide and surgical outcome were not different in the two groups. One of the 32 clinically non-functioning pituitary adenomas had a point mutation at codon 201; none of the seven prolactinomas had these mutations. These results show that gsp mutations are not rare in Korean acromegalic patients and mean tumor size is significantly smaller in acromegalic patients with gsp mutations. Our results also confirm the low frequency of gsp mutations in clinically non-functioning pituitary adenomas and the absence of gsp mutations in prolactinoma.