Solution immersed silicon (SIS)-based biosensors: a new approach in biosensing.

A novel, solution immersed silicon (SIS)-based sensor has been developed which employs the non-reflecting condition (NRC) for a p-polarized wave. The SIS sensor's response is almost independent of change in the refractive index (RI) of a buffer solution (BS) which makes it capable of measuring low-concentration and/or low-molecular-weight compounds.

Quality of life after radiosurgery for cerebral arteriovenous malformation patients who present with seizure.

BACKGROUND AND PURPOSE: This study assessed the quality of life (QOL) and employment status after radiosurgery for arteriovenous malformation (AVM) patients who presented with seizure. METHODS: Between 1997 and 2006, 78 AVM patients who presented with seizure and received radiosurgery were assessed using serial imaging tests, clinical evaluations that included employment status, and a QOL survey. The QOL questionnaire was developed as a retrospective screening tool to estimate the present QOL and the patient's self-rated relative changes (trend values) in QOL after radiosurgery. These results were correlated to one another using the Engel seizure frequency scoring system. RESULTS: The follow-up periods ranged from 48.0 to 151.0 months (mean, 92.5). The mean trend values and mean QOL scores in patients with seizure freedom or AVM obliteration were significantly greater than in patients without these outcomes (all P values < 0.05). Good radiosurgical outcomes were associated with attaining employment (all P values < 0.05). However, differences in employment status were not significant (P = 0.186) despite a higher proportion of patients who described their workplace activity as improved compared with their pre-radiosurgical activity at the last follow-up evaluation. CONCLUSIONS: Radiosurgery may improve QOL and employment status in AVM patients, especially patients who experience seizure freedom or AVM obliteration.

Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the mutation status of PANK2 among Korean patients with pantothenate kinase-associated neurodegeneration (PKAN) and to document the outcome of pallidal deep brain stimulation (DBS). METHODS: Direct sequencing and deletion/duplication analysis of PANK2 were conducted in 12 patients (11 unrelated) with PKAN, diagnosed on the basis of extrapyramidal dysfunction and the 'eye-of-the-tiger sign' on brain magnetic resonance imaging (MRI). Pallidal DBS was conducted in four patients, and the outcomes were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: A PANK2 mutation was identified in both alleles in all patients. The most prevalent mutation was c.1319G>C (p.R440P) in 8/22 mutated alleles (36%). An intragenic deletion ranging from exons 2 to 4 was found in one allele (1/22, 4.5%) using deletion/duplication analysis. The outcome of pallidal DBS was favorable in two patients with atypical PKAN and moderate severity of dystonia. However, two patients with typical PKAN and relatively severe symptoms showed variable responses. CONCLUSIONS: The c.1319G>C (p.R440P) mutation appears to be a founder genotype among Korean patients with PKAN. Furthermore, this study provides additional data for the recent international effort to evaluate the efficacy of pallidal DBS in the treatment of patients with PKAN.

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.

The detection of p53 gene mutation using a microdissection technique in primary intracranial germ cell tumors.

Using a microdissection technique, the contribution of the p53 mutation to tumorigenesis and prognosis in each histological subtype of the intracranial germ cell tumors (GCTs) was evaluated. Nineteen patients had primary intracranial GCTs, including 4 germinomas (GEs), 4 teratomas (TEs), 1 mixed tumor of GE and TE, and 10 mixed GCTs containing non-germinomatous malignant germ cell tumors (NG-MGCTs). After microdissection of specific subtypes, genomic DNA was screened for mutations in exons 5-8 of the p53 gene, using the dideoxyfingerprinting (ddF) followed by direct DNA sequencing. The direct sequencing revealed a total of six mutations in PCR products derived from the five cases (26%) which showed mobility shifts in ddF. Among the six mutations detected, four were missense mutations and two were silent. Missense mutations of the p53 gene tended to occur more frequently in the NG-MGCT component than in the GE or TE components (3/15 vs. 1/12 vs. 0/13). The incidence of missense mutations was not different between the survivors (3/13) and the deceased (1/6). This study suggests the possible role of the p53 gene in the tumori-genesis of NG-MGCT. However, p53 gene mutation did not correlate with the prognosis of NG-MGCT.

Differential effects of cholera toxin and pertussis toxin on the c-fos and c-jun mRNA expression in rat C6 glioma cells.

Cholera toxin (CTX) increased c-fos mRNA level whereas it down-regulated the c-jun mRNA level in rat C6 glioma cells. In contrast to the action of CTX, pertussis toxin (PTX) did not affect either c-fos or c-jun mRNA level. The elevated c-fos mRNA level induced by CTX was significantly inhibited by the co-treatment with dexamethasone (DEX). However, DEX did not affect CTX-induced down-regulation of c-jun mRNA level. Cycloheximide (CHX) increased c-fos and c-jun mRNA levels. CHX caused a super-induction of CTX-induced c-fos mRNA level. Our results suggest that CTX-, but not PTX-, sensitive G-proteins may play an important role for c-fos mRNA up-regulation and c-jun mRNA down-regulation. In addition, DEX appears to have a selective inhibitory action against c-fos mRNA expression regulated by CTX. Ongoing protein synthesis inhibition is required for the superinduction of c-fos, but not c-jun, mRNA induced by CTX.

Continuous monitoring of analyte concentrations.

We have investigated the application of a modified, heterogeneous, competitive enzyme immunoassay for the continuous measurement of small analytes in a medium stream. The analytical system contains two antibodies that are immobilized on spatially separated areas, one binding the analyte (Ab1) and the other binding the enzyme (Ab2). An analyte-enzyme conjugate serves as signal generator. The analyte-enzyme conjugate functions as a heterobifunctional shuttle that can bind to either antibody. A semipermeable membrane retains the enzyme shuttle in the internal volume of the sensor but permits the passage of small analytes from the medium stream. The amount of enzyme bound to Ab1 is inversely proportional and the amount of enzyme bound to Ab2 is directly proportional to the analyte concentration. We have demonstrated that this analytical system (1) can provide a larger total signal; (2) has a sensitivity comparable with conventional competitive immunoassays; (3) does not require the separation of bound from free antigens; and (4) is therefore suitable for the continuous measurement of analytes in a medium stream. With a model system, an increase from 0 ng ml-1 to 20 ng ml-1 of the steroid hormone progesterone and the subsequent fall to 0 ng ml-1 could be monitored.

Conductimetric membrane strip immunosensor with polyaniline-bound gold colloids as signal generator.

For point-of-care examination, an immuno-chromatographic assay system based on conductimetric detection was investigated by utilizing, as signal generator, colloidal gold with polyaniline bound on the metal surface. Although the gold is a widely used label for antibodies to produce colorimetric signals, the tracer does not lend itself for a suitable electric conduction along the gold particles due to the presence of protein barriers (e.g. immunoglobulin and blocking agent) against electron transfer. To overcome this problem, we introduced a conducting polymer, for instance, polyaniline, as a conductivity-modulating agent on the gold surface after immobilizing an antibody specific to human albumin used as model analyte. This novel signal generator amplified the conductimetric signal 4.7 times compared with the plain gold, and the signal was also maximum 2.3-fold higher than that from the photometric system under the same analytical conditions. The latter effect resulted from an exponential pattern in the dose-response curve of the electric signal that was different from the conventional sigmoidal shape.

Visual information processing using bacteriorhodopsin-based complex LB films.

Image extraction and visual information processing using bacteriorhodopsin (bR)-based bioelectronic devices is presented. Image extraction was achieved using a photoreceptor consisting of bR and spiropyran films. The undesired signals from the photoreceptor were automatically eliminated from the whole signal by spiropyran films acting as an optical noise filter that increases the target signal to an undesired signal ratio. For the information processing, the photoreceptor consisting of bR and lipid films deposited with different configurations was used and the target signals were processed to achieve the pattern recognition. The pattern recognition was based on not only the response variability of bacteriorhodopsin, induced by different film configurations, but also on the initial learning process. The input patterns were predicted by simple calculation with the known signals through the initial learning process.

Long-term outcome and growth rate of subtotally resected petroclival meningiomas: experience with 38 cases.

OBJECTIVE: To evaluate the long-term outcome of a subtotally resected residual tumor and to assess its growth rate, we analyzed the records of 38 patients with residual petroclival meningioma. METHODS: Clinical records and radiological findings of 38 cases of petroclival meningioma that were diagnosed and subtotally resected at Seoul National University Hospital between 1981 and 1997 were carefully reviewed. Follow-up imaging studies were reviewed, and Karnofsky performance scale scores at the last follow-up were recorded. The duration of follow-up ranged from 6 to 141 months (mean, 47.5 mo; median, 30 mo). Tumor progression and progression-free survival rates were assessed. The growth rate of a residual tumor was evaluated by measuring the equivalent diameter and the tumor volume serially; the tumor doubling time was calculated, and the predictive factors for determining the growth pattern in residual tumors and the prognosis were analyzed. RESULTS: In 33 (87%) of the 38 patients, Karnofsky performance scale scores at the last follow-up were 80 or above. The median progression-free survival time among patients with subtotally resected tumors was 66 months, and the 5-year progression-free survival rate was 60%. The growth rate of residual tumors was low (volume increase, 4.94 cc/yr; diameter increase, 0.37 cm/yr). The mean tumor doubling time was 8 years. Although there were no significant predictive factors, age and extent of tumor resection seemed to influence the progression-free survival rate. Significant factors affecting the growth rate were age and occurrence of menopause. CONCLUSION: Subtotal resection with or without radiation or radiosurgery should be considered as a suitable treatment option for patients with petroclival meningiomas, especially the elderly, because the growth rate of residual tumors is low.

Gamma knife radiosurgery for brain metastases: prognostic factors for survival and local control.

OBJECT: The authors conducted an analysis of prognostic factors for patient survival and local control of brain metastases after gamma knife radiosurgery. METHODS: In the survival analysis, 53 consecutive patients with 121 lesions treated in the last 2 years were examined. Common primary sites were lung (26 patients), kidney (seven), breast (three), and colon (three). Patient age ranged from 28 to 75 years (median 58 years) and the female/male ratio was 1:0.9. The median tumor volume was 2.1 cm3 (range 0.02-45.5 cm3) and the average prescription dose was 15.4 Gy to the 50% isodose. The median follow up was 12 months (range 1-23 months) and the median survival was 46 weeks. Six-month and 1-year survival rates were 63% and 39%, respectively. Karnofsky Performance Scale score, tumor volume, and presence of extracranial disease were statistically significant prognostic factors (p < 0.05) for survival in multivariate analysis. Number of lesions, patient age, and adjuvant whole-brain radiation therapy were not statistically significant. Ninety-one of 121 lesions with follow-up images were included in the local control analysis. The 1-year actuarial local control rate was 48%. In multivariate analysis smaller volume was associated with better control (p = 0.0043), and, control period of renal cell carcinoma was shorter than that of the other tumor types (p = 0.0070). CONCLUSIONS: Karnofsky Performance Scale score, tumor volume, controlled primary cancer, and absence of extracranial metastases were associated with longer survival in the present study. For local control, tumor volume was a statistically significant factor.

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.

Cerebral sparganosis: clinical manifestations, treatment, and outcome.

Cerebral sparganosis is a rare parasitic disease caused by infestation by the plerocercoid larva of Spirometra mansoni. The authors retrospectively analyzed 17 cases of cerebral sparganosis treated at Seoul National University Hospital between 1986 and 1994. The patients' ages at diagnosis ranged from 6 to 57 years (median 32 years) and the male/female ratio was 13:4. Diagnosis was based on radiological findings, serological test results, operative findings, and histopathological examinations. Characteristic magnetic resonance (MR) findings consisted of widespread white matter degeneration and cortical atrophy, mixed-signal lesion (low in the central and high in the peripheral regions on T2-weighted images) with irregular dense enhancement of central foci and changes in the location and shape of the enhancing lesion in follow-up studies. Ten patients underwent surgical removal of the parasitic lesion, six received medical treatment alone (five with praziquantel and one with antiepileptic drugs), and one underwent insertion of a ventriculoperitoneal shunt and a course of praziquantel. Follow-up periods ranged from 13 to 111 months (mean 49 months). Seven patients who underwent complete removal of the lesion, live worm, or degenerative worm with surrounding granuloma showed a favorable course. Patients who received medical treatment alone or incomplete removal exhibited progression in their neurological deficits and their seizures could not be controlled. Medication with praziquantel seemed to have no killing effect on live worms. The authors conclude that MR imaging is the most valuable modality for the early detection of cerebral sparganosis and that complete surgical removal of granuloma together with worms, whether they are alive or degenerative, is the treatment of choice.

Outcomes of medical treatment of neurocysticercosis: a study of 65 cases in Cheju Island, Korea.

BACKGROUND: Although cysticidal drugs hasten the death and disappearance of the parasite, the long-term prognosis of NCC is still not satisfactory. METHODS: In this study, 65 patients with active neurocysticercosis (NCC) treated with praziquantel or albendazole were retrospectively reviewed to evaluate radiological and clinical outcome. According to worm location, patients were divided into two groups: parenchymal (n = 42) and extraparenchymal NCC (n = 23). The average duration of follow-up was 23 months. RESULTS: In terms of cysticidal effectiveness (73% vs. 50%), seizure control (60% vs. 43%) and symptomatic improvement of non-seizure patients (64% vs. 44%), the outcome of treatment was better in the parenchymal NCC than in the extraparenchymal. Repeated cysticidal treatment was needed in 26% of parenchymal and 39% of extraparenchymal NCC. After treatment, 38% of parenchymal NCC complained of seizure and 35% suffered from headache. Likewise, 27% and 36% of extraparenchymal NCC complained of seizure and headache, respectively. During the follow-up, 7 of 30 patients without initial seizure developed new seizures after medical treatment. CONCLUSION: Despite the development of cysticidal drugs, a considerable number of patients suffer from late neurologic sequelae such as seizure and headache. Therefore continuous attention should be given to the patients after cysticidal treatment. Prevention by health education is emphasized.

A cranio-orbital-zygomatic approach to dumbbell-shaped trigeminal neurinomas using the petrous window.

We applied a cranio-orbital-zygomatic approach that extends the temporal craniotomy more posteriorly and minimizes the frontal orbitotomy of an ordinary orbitozygomatic approach in order to provide wide access to the already eroded petrous apices along the long axis of trigeminal neurinomas. We treated seven dumbbell-shaped trigeminal neurinomas between 1991 and 1998 (mean follow-up, 38 months; range, 9 to 109 months). The configuration of the tumor mass was assessed on magnetic resonance imaging by measuring its long diameter in the middle and posterior fossae and the width of petrous erosion. Tumors were then classified into five types based on their distribution over the petrous ridge. Total removal was achieved in six patients, who showed no evidence of tumor recurrence during the follow-up period. The only major complication was one case of anesthesia dolorosa. The one patient with a subtotal removal developed a recurrence 12 months after surgery, in the posterior fossa. The cranioorbital-zygomatic approach could be an effective method for removing dumbbell-shaped trigeminal neurinomas, particularly in cases of wide petrous erosion from the tumor. If, however, the tumor has a larger posterior fossa component, this approach may not provide adequate exposure to achieve a total resection.

Expansion of human bone marrow progenitor cells in a high cell density continuous perfusion system.

We describe here a continuous perfusion bioreactor system that enables a population of unselected human mononuclear bone marrow cells obtained from adult donors to expand up to 20 to 25-fold over a two-week period. Colony-forming units of granulocyte-macrophage (CFU-GM) progenitor cells expand 10 to 30-fold. These expansions depend on the gas phase oxygen concentration, the seeding density and time of cell harvest. Under operating conditions that allow for good cell proliferation, 3 to 4 million mononuclear cells can be obtained per square centimeter, with 0.5 to 0.8% being progenitor cells. Autologous human sera supported cell expansion as efficiently as animal sera. Increasing the size of the perfusion system to produce a clinically meaningful number of CFU-GMs could have important applications in bone marrow transplantation therapies.

Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in parkinsonism.

OBJECTIVE: To investigate the role of spinocerebellar ataxia type 17 (SCA17) in the development of parkinsonism. METHOD: We screened 1,155 parkinsonian patients (931 with Parkinson disease and 224 with multiple system atrophy) and 400 normal subjects for SCA17. 99mTc-TRODAT-1 SPECT was used to evaluate the striatal dopamine transporter (DAT) status. RESULTS: Trinucleotide expansion in the SCA17 gene was found in 10 parkinsonian patients (8 with Parkinson disease, 2 with multiple system atrophy) using 42 repeats as an upper normal limit. The repeat sizes in the patients ranged from 43 to 46, which are considered to be low-range expansions. All patients had interrupted sequences. Three probands and three asymptomatic carriers underwent 99mTc-TRODAT-1 SPECT. Striatal DAT binding was markedly reduced in all probands and mildly decreased in one asymptomatic carrier. Among the 400 normal control subjects, there was one individual with an expansion of 44 repeats, another with 43 repeats, and two with 42 repeats. Striatal DAT binding was decreased not only in the control subjects with 44 or 43 repeats, but in ones with 42 repeats, suggesting that an expansion as low as 42 repeats might constitute a susceptibility gene for parkinsonism. CONCLUSIONS: Low-range expansion of the SCA17 gene is not a rare genetic cause of parkinsonism without ataxia in our population. Reduced penetrance or variable expressivity in low-range expansion might be an explanation for the blurred cutoff point for normal expansion in SCA17.

Isolation and characterization of outer root sheath melanocytes of human hair follicles.

BACKGROUND: Outer root sheath melanocytes (ORSM) are not yet routinely cultured and their biology is not known in detail because of their relatively low numbers in the hair follicle and their limited proliferative capacity in in vitro culture in routine media. OBJECTIVES: To develop a method for culturing ORSM more easily and to investigate the length of telomeres and antigenic characteristics of ORSM compared with epidermal melanocytes (EM). METHODS: Hair follicles were obtained from three Korean individuals during hair transplantation surgery. Single-cell suspensions of the outer root sheath were made and cultured in melanocyte growth medium with stem cell factor. After 21 days, second-passage outer root sheath keratinocytes (ORSK) (2 x 10(4) mL(-1) MGM) were added into the culture plates. We studied the proliferation pattern, morphological and antigenic characteristics of ORSM for each passage of cultured cells, and observed ORSM telomere length. RESULTS: We established an ORSM culture method using ORSK. Two morphologically different ORSM types were obtained in the primary cultures. At the end of primary culture, ORSM appeared as whitish-cream pellets. The proliferation pattern of ORSM showed a sigmoidal shape, the accumulated numbers of population doublings showed a plateau after approximately 5 months, and senescence occurred at approximately 33 +/- 5 accumulated population doublings. The length of ORSM telomeres continued to shorten as the cells proliferated. In contrast, EM showed a marked proliferation from the early proliferation period which formed a plateau pattern towards the later period, and the number of accumulated population doublings was estimated to be 18 +/- 5 after 2 months. ORSM in the primary culture reacted variably with l-dihydroxyphenylalanine (DOPA): some cells were DOPA negative, some DOPA positive. There were some different antigenic expressions of microphthalmia-associated transcription factor (MITF) showing cytoplasmic expression in ORSM and nuclear expression in EM. By nuclear extraction and Western blotting, we showed that MITF expression of ORSM was marked in the cytoplasm and minimal in the nucleus. Antigenic expression of MITF and Bcl-2 gradually decreased with increasing passage number, whereas tyrosinase-related protein-1 expression did not change. CONCLUSIONS: Culture of ORSM requires ORSK or ORSK-related factors; ORSM have greater proliferation potential and show different MITF antigenic expression compared with EM; and the length of ORSM telomeres shortens with repeated proliferation.

Clinical analysis of vertebrobasilar dissection.

BACKGROUND: The natural history of vertebrobasilar artery dissection (VAD) is not fully known. The purpose of this study was to review the clinical outcome of the patients with VAD, then to propose an appropriate management strategy for VAD. METHOD: From 1992 to 2004, 35 VAD patients admitted to our institutes were retrospectively reviewed. There were 28 men and 7 women, whose age ranged from 4 to 67 years with a mean age of 44 years. Angiography was assessed to document the shape, and location of the dissecting aneurysm with respect to the posterior inferior cerebellar artery (PICA). A modified Rankin score was assigned for functional outcome. The functional outcome scores were analyzed according to the patient's age, gender, hypertension history, the pattern of initial manifestation, angiographic shape of VAD, angiographic location of VAD, treatment modality. FINDINGS: There was no statistically significant difference between the functional outcome with age, gender, trauma history and past medical history of hypertension. Of 35 patients, 22 presented with SAH, 11 with ischemic symptoms and 2 were incidentally detected. The patients without SAH had a better functional outcome than those with SAH (p = 0.029). There was statistical significance between Hunt-Hess (H-H) grade and clinical outcome (p = 0.032). The shape and location of VAD was not significantly related to the functional outcome (p = 0.294, 0.840). But all the cases of rebleeding and mortality (except one case with initially poor H-H grade) developed exclusively in patients with aneurysms. There was no statistically significant correlation between the treatment modality and the outcome (p = 0.691). CONCLUSION: The VAD patients with SAH would be recommended to be managed by either surgical or endovascular treatment, but those without SAH, could be managed conservatively with antiplatelet therapy and/or anticoagulation.