bluuebunny/crossref_metadata_2025 huggingface dataset:
CD133+ and CD133− Glioblastoma-Derived Cancer Stem Cells Show Differential Growth Characteristics and Molecular Profiles
Authors: Beier Dagmar , Hau Peter , Proescholdt Martin , Lohmeier Annette , Wischhusen Jörg , Oefner Peter J. , Aigner Ludwig , Brawanski Alexander , Bogdahn Ulrich , Beier Christoph P.
Published: May 2007

Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)–derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell–like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133+ subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133− tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133− glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133+ CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133− tumor cells with apparent stem cell–like properties but distinct molecular profiles and growth characteristics in vitro and in vivo. [Cancer Res 2007;67(9):4010–5]
The Tyrosine Phosphatase Shp2 Interacts with NPM-ALK and Regulates Anaplastic Lymphoma Cell Growth and Migration
Authors: Voena Claudia , Conte Chiara , Ambrogio Chiara , Boeri Erba Elisabetta , Boccalatte Francesco , Mohammed Shabaz , Jensen Ole N. , Palestro Giorgio , Inghirami Giorgio , Chiarle Roberto
Published: May 2007

Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry–based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine phosphatase Shp2 as a candidate substrate. We found that NPM-ALK was able to bind Shp2 in coprecipitation experiments and to induce its phosphorylation in the tyrosine residues Y542 and Y580 both in HEK293 cells and ALCL cell lines. In primary lymphomas, antibodies against the phosphorylated tyrosine Y542 of Shp2 mainly stained ALK-positive cells. In ALCL cell lines, Shp2-constitutive phosphorylation was dependent on NPM-ALK, as it significantly decreased after short hairpin RNA (shRNA)–mediated NPM-ALK knock down. In addition, only the constitutively active NPM-ALK, but not the kinase dead NPM-ALKK210R, formed a complex with Shp2, Gab2, and growth factor receptor binding protein 2 (Grb2), where Grb2 bound to the phosphorylated Shp2 through its SH2 domain. Shp2 knock down by specific shRNA decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and of the tyrosine residue Y416 in the activation loop of Src, resulting in impaired ALCL cell proliferation and growth disadvantage. Finally, migration of ALCL cells was reduced by Shp2 shRNA. These findings show a direct involvement of Shp2 in NPM-ALK lymphomagenesis, highlighting its critical role in lymphoma cell proliferation and migration. [Cancer Res 2007;67(9):4278–86]
An Orally Available Small-Molecule Inhibitor of c-Met, PF-2341066, Exhibits Cytoreductive Antitumor Efficacy through Antiproliferative and Antiangiogenic Mechanisms
Authors: Zou Helen Y. , Li Qiuhua , Lee Joseph H. , Arango Maria E. , McDonnell Scott R. , Yamazaki Shinji , Koudriakova Tatiana B. , Alton Gordon , Cui Jingrong J. , Kung Pei-Pei , Nambu Mitchell D. , Los Gerrit , Bender Steven L. , Mroczkowski Barbara , Christensen James G.
Published: May 2007

The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been implicated in the progression of several human cancers and are attractive therapeutic targets. PF-2341066 was identified as a potent, orally bioavailable, ATP-competitive small-molecule inhibitor of the catalytic activity of c-Met kinase. PF-2341066 was selective for c-Met (and anaplastic lymphoma kinase) compared with a panel of >120 diverse tyrosine and serine-threonine kinases. PF-2341066 potently inhibited c-Met phosphorylation and c-Met–dependent proliferation, migration, or invasion of human tumor cells in vitro (IC50 values, 5–20 nmol/L). In addition, PF-2341066 potently inhibited HGF-stimulated endothelial cell survival or invasion and serum-stimulated tubulogenesis in vitro, suggesting that this agent also exhibits antiangiogenic properties. PF-2341066 showed efficacy at well-tolerated doses, including marked cytoreductive antitumor activity, in several tumor models that expressed activated c-Met. The antitumor efficacy of PF-2341066 was dose dependent and showed a strong correlation to inhibition of c-Met phosphorylation in vivo. Near-maximal inhibition of c-Met activity for the full dosing interval was necessary to maximize the efficacy of PF-2341066. Additional mechanism-of-action studies showed dose-dependent inhibition of c-Met–dependent signal transduction, tumor cell proliferation (Ki67), induction of apoptosis (caspase-3), and reduction of microvessel density (CD31). These results indicated that the antitumor activity of PF-2341066 may be mediated by direct effects on tumor cell growth or survival as well as antiangiogenic mechanisms. Collectively, these results show the therapeutic potential of targeting c-Met with selective small-molecule inhibitors for the treatment of human cancers. [Cancer Res 2007;67(9):4408–17]
Influence of Tumor Cell and Stroma Sensitivity on Tumor Response to Radiation
Authors: Ogawa Kazuhiko , Boucher Yves , Kashiwagi Satoshi , Fukumura Dai , Chen David , Gerweck Leo E.
Published: May 2007

In this study, we evaluated the role of tumor cell and tumor stroma sensitivity as determinants of radiation-induced tumor growth delay. A DNA double-strand break repair–defective DNA-PKcs−/− tumor cell line and its radioresistant DNA-PKcs+/+–transfected counterpart were used to initiate tumors in nude and hypersensitive severe combined immunodeficient (SCID) mice. Insertion of the human DNA-PKcs+/+ gene substantially increased the intrinsic radioresistance of the DNA-PKcs−/− tumor cells and substantially decreased tumor response to radiation in both nude and hypersensitive SCID mice. Tumor cell radiosensitivity was the major determinant of tumor response in nude mice. In SCID mice, both tumor cell sensitivity and radiation-induced stromal damage contributed to response. The relative contribution of host and tumor cell sensitivity on tumor response was unchanged for single doses of 1 × 15 and 6 × 3 Gy–fractionated dose irradiation. [Cancer Res 2007;67(9):4015–21]
Integration of Somatic Deletion Analysis of Prostate Cancers and Germline Linkage Analysis of Prostate Cancer Families Reveals Two Small Consensus Regions for Prostate Cancer Genes at 8p
Authors: Chang Bao-li , Liu Wennuan , Sun Jishan , Dimitrov Latchezar , Li Tao , Turner Aubrey R. , Zheng Siqun L. , Isaacs William B. , Xu Jianfeng
Published: May 2007

The evidence for tumor suppressor genes at 8p is well supported by many somatic deletion studies and genetic linkage studies. However, it remains a challenge to pinpoint the tumor suppressor genes at 8p primarily because the implicated regions are broad. In this study, we attempted to narrow down the implicated regions by incorporating evidence from both somatic and germline studies. Using high-resolution Affymetrix arrays, we identified two small common deleted regions among 55 prostate tumors at 8p23.1 (9.8–11.5 Mb) and 8p21.3 (20.6–23.7 Mb). Interestingly, our fine mapping linkage analysis at 8p among 206 hereditary prostate cancer families also provided evidence for linkage at these two regions at 8p23.1 (5.8–11.2 Mb) and at 8p21.3 (19.6–23.9 Mb). More importantly, by combining the results from the somatic deletion analysis and genetic linkage analysis, we were able to further narrow the regions to ∼1.4 Mb at 8p23.1 and ∼3.1 Mb at 8p21.3. These smaller consensus regions may facilitate a more effective search for prostate cancer genes at 8p. [Cancer Res 2007;67(9):4098–103]
A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent
Authors: Landis-Piwowar Kristin R. , Huo Congde , Chen Di , Milacic Vesna , Shi Guoqing , Chan Tak Hang , Dou Q. Ping
Published: May 2007

The most abundant and biologically active green tea catechin, (−)-epigallocatechin-3-gallate or (−)-EGCG, has been shown to act as a proteasome inhibitor and tumor cell death inducer. However, (−)-EGCG is unstable under physiologic conditions and has poor bioavailability. Previously, in an attempt to increase the stability of (−)-EGCG, we introduced peracetate protections to its reactive hydroxyl groups and showed that this peracetate-protected (−)-EGCG [Pro-EGCG (1); formerly named compound 1] could be converted into (−)-EGCG under cell-free conditions. In the current study, we provide evidence that when cultured human breast cancer MDA-MB-231 cells were treated with Pro-EGCG (1), (−)-EGCG was not only converted but also accumulated, accompanied by enhanced levels of proteasome inhibition, growth suppression, and apoptosis induction, compared with cells treated with natural (−)-EGCG. To investigate the potential use of Pro-EGCG (1) as a novel prodrug that converts to a cellular proteasome inhibitor and anticancer agent in vivo, MDA-MB-231 tumors were induced in nude mice, followed by treatment with Pro-EGCG (1) or (−)-EGCG for 31 days. Results of this in vivo study showed a significant inhibition of breast tumor growth by Pro-EGCG (1), compared with (−)-EGCG, associated with increased proteasome inhibition and apoptosis induction in tumor tissues. In conclusion, we have shown that Pro-EGCG (1) increases the bioavailability, stability, and proteasome-inhibitory and anticancer activities of (−)-EGCG in human breast cancer cells and tumors, suggesting its potential use for cancer prevention and treatment. [Cancer Res 2007;67(9):4303–10]
Phosphorylation and Activation of Cell Division Cycle Associated 8 by Aurora Kinase B Plays a Significant Role in Human Lung Carcinogenesis
Authors: Hayama Satoshi , Daigo Yataro , Yamabuki Takumi , Hirata Daizaburo , Kato Tatsuya , Miyamoto Masaki , Ito Tomoo , Tsuchiya Eiju , Kondo Satoshi , Nakamura Yusuke
Published: May 2007

Through genome-wide gene expression analysis of lung carcinomas, we detected in the great majority of lung cancer samples cotransactivation of cell division cycle associated 8 (CDCA8) and aurora kinase B (AURKB), which were considered to be components of the vertebrate chromosomal passenger complex. Immunohistochemical analysis of lung cancer tissue microarrays showed that overexpression of CDCA8 and AURKB was significantly associated with poor prognosis of lung cancer patients. AURKB directly phosphorylated CDCA8 at Ser154, Ser219, Ser275, and Thr278 and seemed to stabilize CDCA8 protein in cancer cells. Suppression of CDCA8 expression with small interfering RNA against CDCA8 significantly suppressed the growth of lung cancer cells. In addition, functional inhibition of interaction between CDCA8 and AURKB by a cell-permeable peptide corresponding to 20-amino acid sequence of a part of CDCA8 (11R-CDCA8261–280), which included two phosphorylation sites by AURKB, significantly reduced phosphorylation of CDCA8 and resulted in growth suppression of lung cancer cells. Our data imply that selective suppression of the CDCA8-AURKB pathway could be a promising therapeutic strategy for treatment of lung cancer patients. [Cancer Res 2007;67(9):4113–22]
Preclinical Evaluation of EC145, a Folate-Vinca Alkaloid Conjugate
Authors: Reddy Joseph A. , Dorton Ryan , Westrick Elaine , Dawson Alicia , Smith Terri , Xu Le-Cun , Vetzel Marilynn , Kleindl Paul , Vlahov Iontcho R. , Leamon Christopher P.
Published: May 2007

We recently developed a new group of folate-conjugated Vinca alkaloids, one of which, EC145, emerged as a candidate for clinical development. Brief treatment of nude mice bearing ∼100 mm3 folate receptor-positive human xenografts led to complete response (CR) in 5/5 mice and cures (i.e., remission without a relapse for >90 days post-tumor implantation) in 4/5 mice. Multiple CRs and cures were also noted when EC145 was used to treat mice initially bearing tumors as large as 750 mm3. Likewise, complete cures (5/5) resulted following the treatment of an aggressive folate receptor–positive J6456 lymphoma model. The activity of EC145 was not accompanied by noticeable weight loss or major organ tissue degeneration. Furthermore, no significant antitumor activity (0/5 CR) was observed in EC145-treated animals that were co-dosed with an excess of a benign folate ligand, thus demonstrating the target-specific activity of EC145. The enhanced therapeutic index due to folate conjugation was also evidenced by the fact that the unconjugated drug (desacetylvinblastine monohydrazide) was found to be completely inactive when administered at nontoxic dose levels and only marginally active when given at highly toxic dose levels. Subsequent dose regimen studies confirmed that EC145 given on a more frequent, qdx5 schedule resulted in the most effective antitumor response as compared with an equivalent total dose given on thrice- or single-injection-per-week schedule. Taken together, these studies show that EC145 has significant antiproliferative activity and tolerability, thus lending support to an ongoing phase 1 trial for the treatment of advanced malignancies. [Cancer Res 2007;67(9):4434–42]
Institution Type-Dependent High Prevalence of Dementia in Long-Term Care Units
Authors: Chen Ta-Fu , Chiu Ming-Jang , Tang Li-Yu , Chiu Yueh-Hsia , Chang Shu-Feng , Su Che-Long , Chen Shaw-Ji , Lin Chung-Wei , Shih Wan-Yu , Chen Tony Hsiu-Hsi , Chen Rong-Chi
Published: May 2007

Background/Aims: It is estimated that there are 90,000 patients with dementia in the 23 million habitants of Taiwan, with a few institutions specialized in dementia care. To assess the need of institutional care for dementia, we investigated the institution prevalence of dementia. Methods: We performed stratified randomized sampling of elder residents from different types of institutions in different regions of Taiwan. A 2-stage survey with screening and clinical confirmation was carried out in 2004. Results: In total, 1,525 residents aged 65 years and over in 60 institutions participated in the study in which 1,308 elders completed the 2-stage survey. Among these, 631 elders were diagnosed as having dementia. The dementia prevalence was 26.8% in the residential houses, 61.8% in the assisted living facilities and 64.5% in the nursing homes. Vascular dementia was the leading cause of dementia in the institutions. Old age, diabetes mellitus and family history of dementia increased risks for both Alzheimer’s disease and vascular dementia. Conclusion: The investigation showed that the prevalence of dementia in the long-term care units of Taiwan was much higher than those from community studies and the high prevalence in the institutions depended on the type of the long-term care unit.
Medial Medullary Infarct Aggravates Central Poststroke Pain Caused by Previous Lateral Medullary Infarct
Authors: Kim Jong S.
Published: May 2007

Background: Although the pathogenesis of central poststroke pain (CPSP) remains obscure, interactions between the spinothalamic tract and lemniscal sensory tract may be involved in its pathogenic mechanism. Case Description: A patient developed lateral medullary infarction, which produced contralateral spinothalamic sensory deficits and subsequent CPSP. The CPSP gradually improved until the development of ipsilateral medial medullary infarction 26 months later, which was associated with mild hemiparesis and lemniscal sensory deficits. The ipsilateral medial medullary infarction immediately aggravated the CPSP to its previous level. Conclusion: This observation has implications regarding the pathogenesis of CPSP. CPSP may be related to hyperexcitation of the spinothalamic pathway by the reticulothalamic system, which in turn is modulated by the medial lemniscus pathway.
First-Ever Ischemic Stroke in Very Old Asians: Clinical Features, Stroke Subtypes, Risk Factors and Outcome
Authors: Lee Meng , Huang Wen-Yi , Weng Hsu-Huei , Lee Jiann-Der , Lee Tsong-Hai
Published: May 2007

Background: Prior studies have been conducted in very old white and black patients. However, stroke in very old Asians has not been studied. Methods: This study retrospectively reviewed the records of first-ever ischemic stroke patients admitted to the Chiayi Chang Gung Memorial Hospital in the middle part of Taiwan from January 2002 to December 2005. Clinical features, stroke subtypes, risk factors, acute ward mortality, length of acute ward stay, medical complications and medication for secondary stroke prevention at discharge were compared in 2 groups of first-ever ischemic stroke patients (one ≧80 and the other <80 years old). Results: Aged patients (≧80 years old) had a higher proportion of conscious impairment at admission, a longer acute ward stay, a higher incidence of total anterior circulation infarct and a lower frequency of lacunar infarct, more frequent atrial fibrillation and less frequent diabetes mellitus, hyperlipidemia and smoking habits, and a higher incidence of pneumonia, urinary tract infection and upper gastrointestinal bleeding. Conclusions: Understanding the risk factors and medical complications in very old stroke patients may help improve the stroke prevention strategy and the quality of stroke patient management.
Beneficial Augmentation following Dorsal Column Stimulation in Some Neurological Diseases
Authors: Davis Ross , Gray Edward , Kudzma Joanne
Published: May 2007

101 patients with multiple sclerosis and other demyelinating diseases have undergone dorsal column stimulation (DCS) during the past 6 years. DCS augmented weakened neurological functions in 94 patients. Varying improvements were seen in general strength, balance and gait, sensory modalities, speech, and bladder function with an important increase in endurance. Two different DCS systems were implanted: 65 patients had a radio frequency stimulator and 36 had a totally implantable programmable stimulator. Except for the first 4 patients, who underwent an initial trial of DCS, permanent implantation of the stimulation system was done as the initial procedure in the series. 16 patients died of their disease or other causes unrelated to the stimulator. DCS is a safe and efficacious method for augmenting the neurological function in most selected patients and can lead to an improved quality of life.
Technological Problems of Spinal Cord Stimulation Systems: A Clinical Perspective
Authors: Sharkey P.C.
Published: May 2007

Technological problems of spinal cord stimulation, from the clinician''s standpoint are the topics of this review of a round table discussion. Surgical aspects of spinal cord stimulation system implant procedures are reviewed. Safety and reliability of the methods and systems are discussed. Problems with durability and fixation of epidural electrodes are reported, and solutions are sought from the continued interaction of clinicians and biomedical engineers in the future development of methods and systems.
Results of Spinal Cord Stimulation in Multiple Sclerosis
Authors: Cook Albert W. , Taylor J. Kenneth , Nidzgorski Florence
Published: May 2007

The results of spinal cord stimulation by various methods in 204 patients with multiple sclerosis are presented.
Clinical Evaluation of the Effect of Spinal Cord Stimulation on Motor Performance in Patients with Upper Motor Neuron Lesions
Authors: Campos R.J. , Dimitrijevic M.M. , Faganel J. , Sharkey P.C.
Published: May 2007

The effect of chronic electrical stimulation of the spinal cord was evaluated in a group of 24 patients with multiple sclerosis, spinal cord injury, and degenerative disorders of the central nervous system. The systems for stimulation had been implanted from 12 to 30 months prior to completion of evaluation. At the time of completion of evaluation, 23 of the 24 patients still had implanted systems, although 6 of them had not used spinal cord stimulation because of no noticeable effect. In 3 patients stimulation had been disconnected because of technical failure of the system. In 1 patient the system had been removed 8 weeks after implantation because of inflammation in the under-skin receiver pocket. The effects on motor performance of the remaining 14 patients who had continuously active systems were improved bladder control, diminished spasticity, improved movement coordination, and increased endurance.
Examination of Possible Mechanisms by Which Stimulation of the Spinal Cord in Man Relieves Pain
Authors: Campbell James N.
Published: May 2007

Stimulation of the spinal cord may be very helpful in controlling chronic pain. Traditionally it has been thought that pain control derives from antidromic activation of large-diameter primary afferents in the posterior columns, which inhibits activation of second-order neurons. Evidence against this hypothesis is presented. In addition, it is pointed out that stimulation of the anterolateral quadrant contralateral to the side of pain may require less current for pain control than stimulation with electrodes over the posterior cord. It is suggested that ''frequency-related conduction block'' in the spinothalamic tract or in Lissauer''s tract may play a role in pain relief. Because of uncertainty about the mechanism it is suggested that the term ''dorsal column stimulation'' be replaced by ''spinal axis stimulation''.
Electrical Stimulation of the Spinal Cord and Peripheral Nerves for Pain Control
Authors: Long Don M. , Erickson Donald , Campbell James , North Richard
Published: May 2007

Patients who underwent implantation of dorsal column stimulators from 1970 to 1973 were reviewed 7–10 years following stimulation. The number who achieved satisfactory pain relief was not significant. The criteria for selecting these patients were reviewed utilizing those now used in 1980. 50% of the patients originally selected would now be rejected for psychological or drug-related reasons. This long-term evaluation indicates no benefit to the patients treated with spinal cord stimulation. However, it appears that psychological factors were the most important reasons for failure. A smaller group of patients studied for 3–5 years following implantation of epidural spinal cord stimulators achieved a 70% pain control rate. Selection factors that explain these differences are discussed.
Electromyographic Activity of Neck Muscles in Patients Affected by Retrocollis under the Influence of Stimulation and Coagulation of the Prestitial Nucleus of the Midbrain
Authors: Hassler R. , Vasilescu C. , Dieckmann G.
Published: May 2007

In 2 patients with retrocollis, the positive effects obtained by stereotactic high frequency coagulation of the prestitial nucleus on the tonic activity of the neck muscles were studied electromyographically and clinically. Before the stereotactic therapy, electromyographic recordings at rest were recorded from the musculi splenii. During stimulation of the prestitial nucleus at frequencies of 8,25 and 50 Hz, the EMG activity at rest diminished in frequency and amplitude and ultimately disappeared. Passage from the EMG recordings at rest to electrical silence took place, in one case, through a rhythmic activity of potentials grouped at 11/s. After coagulation of the prestitial nucleus, the involuntary contractions of neck muscles disappeared and electrical silence occurred. On reexamination 1 month later, the positive results were still present.
A Survey of Infections in Stereotactic Surgery
Authors: Hood Terry W. , Yap Jesse C.
Published: May 2007

In 365 consecutive intracranial stereotactic procedures over a 6-year period, there were three postoperative infections; 1 case of increased neurological deficit and 1 of fatality. Staphylococcus aureus was the most common organism involved; however, multiple organisms were seen in 2 cases. Multiplicity of organisms necessitated the use of a broad spectrum of antibiotics in the preoperative and postoperative periods. The method described has permitted an infection rate which compares favorably to other reports in the literature. Perioperative antibiotics, antibiotic-containing irrigation solutions, and careful attention to sterile techniques seem to be instrumental in maintaining a low infection rate in our study. Since the new spheroid design has been used, there have been no infections.
Surgical Possibilities for Alleviation of Axial Dyskinesias – Comparison with Forced Movements of the Head and Eyes
Authors: Stejskal L. , Vladyka V. , Tománek Z.
Published: May 2007

107 patients suffering from axial dyskinesias (torticollis and torsion dystonia) were observed at our clinic over a period of 10 years. In 15 patients, stereotactic lesions involving the head-turning bundle at the caudatocapsular level, which mediates forced adversive movements, were performed. In 70% good to excellent results were confirmed. However, differences between forced adversive movements and torticollis were identified. There are striking motor and motivational similarities between torticollis and ritualized fixed action patterns of low-ranking subjects. The aetiology of axial dyskinesias, especially of torticollis, is multifactorial, long-term psychic stress being an important factor. The relationship of axial dyskinesias, especially of torticollis, to compulsive neuroses is discussed, and Mazar's 'adversive' target area is identified as a partial or-bitomedial leukotomy.
Lesions Made in the Rabbit Brain to Assist the Design and Use of Electrodes for Amygdalotomy in Man
Authors: Levi F.P. , Girgis M.
Published: May 2007

The lesion sizes produced by passing anodic currents of up to 10 mA through gold electrodes implanted in rabbit brains have been estimated histologically. The information has been used to design sheaves of similar electrodes implanted in human brains for amygdalotomy. The maximum current that can be passed through an electrode without generating an excessive temperature has been defined approximately.
Influence of Dorsal Column Stimulation upon Human Thalamic Somatosensory-Evoked Potentials
Authors: Gildenberg P.L. , Murthy K.S.K.
Published: May 2007

2 patients with previously implanted dorsal column stimulators underwent basal thalamotomy for the treatment of pain, which provided the opportunity to record evoked potentials from the intralaminar (IL) and ventroposterolateral (VPL) areas of the thalamus. Short latency evoked potentials recorded from VPL were not influenced by dorsal column stimulation. However, very long latency (500 ms) potentials recorded bilaterally in IL were modified by stimulation of the dorsal columns of the spinal cord at frequencies between 20 and 40 Hz.
Visual Phenomena Evoked by Electrical Stimulation of the Human Brain Stem
Authors: Tasker R.R. , Organ L.W. , Hawrylyshyn P.
Published: May 2007

19 visual effects have been elicited out of 9,383 sites during stimulation mapping for physiological localization during stereotactic surgery. It is proposed that three visual pathways can be recognized during subcortical electrical stimulation in man. The optic tract and geniculocalcarine pathway, projecting to area 17, are recognizable by the production of contralateral coloured phosphenes. The tectopulvinar pathway projecting to areas 18 and 19 is recognizable by the eliciting of contralateral or bilateral colourless phosphenes or ''negative'' visual effects, the latter presumably reflecting inhibitory collicular influences. Finally, deep responses, consisting of apparent movement of the visual fields, intermingled with ‘negative’ visual and oculomotor effects, suggest activation of a visual-oculomotor coordinating system.
Stereotactic Evacuation of Large Intracerebral Hematoma
Authors: Higgins Alfred C. , Nashold Jr. Blaine S.
Published: May 2007

Despite the declining incidence of strokes, statistics regarding intracerebral hemorrhage indicate a relatively stable incidence in this form of cerebral insult over the past 20 years. Intracerebral hemorrhage accounts for 10% of all strokes, and is fatal to 50–60% of its victims. Until the advent of computer-assisted tomography, surgical intervention offered little benefit to patients suffering primary hemorrhage within the deep gray structures of the cerebral hemispheres. Technical advances in both diagnostic and therapeutic instrumentation now permit stereotactic subtotal evacuation of deep intracerebral hematomas.
Multitarget Technique in Parkinson Surgery
Authors: Tóth Szabolcs , Vajda Janos
Published: May 2007

In the past 10 years, experience has been gained with combined VL-thalamotomy, pallidotomy and dentatomy using chronically implanted electrodes in Parkinson''s disease. In the vast majority of cases, symptoms ceased surprisingly for 10–14 days just after stereotactic exploration of these motor centers. Clinical neurophysiological investigations (evoked responses, motor effects) show where consecutive lesions will be permanently effective at definitive coagulation. The physiological basis of these findings are discussed and a sophisticated therapeutic protocol is advised.
VOI Thalamotomy in Spasmodic Torticollis
Authors: von Essen C. , Augustinsson L.-E. , Lindqvist G.
Published: May 2007

We performed stereotactic VOI thalamotomy as the only surgical treatment in spasmodic torticollis in 17 patients since 1972. The patients selected for surgery mainly presented horizontal torticollis. All the patients improved after unilateral thalamotomy. In most cases there was a delay in improvement varying from 3 months to 2–3 years postoperatively. The severity of the psychic disturbances present in most patients at the time of onset of their torticollis did not have any relevance to their final outcome after surgery.
A Fully Interfaced Computerized Tomographic-Stereotactic Surgical System
Authors: Koslow Maxim , Abele Manlio G.
Published: May 2007

A fully interfaced computerized tomographic system has been designed and constructed. A prototype Philips Medical Systems Inc. translate-rotate body scanner has been modified to accommodate a specially designed head holder and stereotactic guide. A high resolution partial scanning algorithm is used to achieve improved spatial resolution in comparison to conventional algorithms. Integration of scanning data with the geometry of the guide system is achieved with software control.
Stereotactic CT Scan and Its Correlation with the Neural Activity of Deep Structures
Authors: Ohye C. , Nakajima H. , Kawashima Y. , Miyazaki M.
Published: May 2007

An attempt has been made to visualize beforehand a brain section through which an electrode would pass to reach the target point in stereotactic thalamotomy for the treatment of tremor. On the basis of several craniometric measurements of a plain craniogram (lateral view), the level of the intercommissural line could be approximately estimated and a tentative target point set on the craniogram. Then, a line is drawn to connect this target point and the bregma. Extrapolating this line, an angle between the Reid baseline and this line could be measured in order to transfer the line to the scalp. With the aid of a GE scanner (GE-CT/T-X2), several 5-mm thick sections are made parallel to this line including the tentative target point. Among these images of CT scan thus made, referring to the foramen of Monro and the aqueduct (either of which might be visualized) one of the sections would be chosen as a tentative plane through which the electrode would pass. On the operation day, a burr hole should be made on or near the line used for CT scanning and drawn on the scalp, so the electrode tract will coincide with the CT scan image. GE scan images are clear enough to estimate the range of gray matter, white matter, caudate nucleus and thalamus. The neural activities of the deep structures recorded during the operation by stepping displacement of the electrode are correlated with this CT scan image. So far, the coincidence of both findings are satisfactory and of great value in this kind of blind operation.
Stereotactic Biopsy in Acoustic Tumors
Authors: Norén Georg , Collins V. Peter
Published: May 2007

5 cases of tumors of the cerebellopontine angle were subjected to stereotactic puncture and biopsy for various reasons (preoperative differential diagnostic difficulties, cyst evacuation, evaluation of the effect of stereotactic radiosurgery). Material for cytology was aspirated in all 5 cases; in addition, a spiral biopsy was obtained in 2. The specimens enabled a satisfactory morphological judgement in 4 cases, while in 1 case the emptying of a cyst did not provide adequate material. No untoward effects were observed.
Technical Problems and Advances in the Cerebellar-Stimulating Systems Used for Reduction of Spasticity and Seizures
Authors: Davis Ross , Gray Edward F.
Published: May 2007

A series of 300 patients were implanted for chronic cerebellar stimulation (CCS) from February 1974 to June 1980. The charge density was in the range of 0.7–1.6 µCi/cm2/phase. There is a very narrow range of stimulation in which CCS is effective. Increasing above the range, clinical benefits cease; at levels over 10 µCi/cm2/phase, damage to the underlying conducting elements occurs which renders the prosthesis ineffective. Periodic monitoring of the implanted equipment is mandatory for a successful clinical program. Scalp recordings and radiography have detected a 53% failure rate in the I-108 RF linked system. The failed receivers were replaced with more reliable I-110 receivers and later with a fully implantable pulse generator. No change has been detected in the electrode button-cortex interface when measuring the access resistance up to 5 years later.
Stereotactic Neurosurgery in Experimental Animals
Authors: Ilinsky I.A. , Kultas-Ilinsky K. , Young P.A. , Smith K.R.
Published: May 2007

A stereotactic method, based on the correlation of intracerebral ra-diological and anatomical landmarks, was developed for application in experimental animals. To make possible the use of this method, particularly in the cat, a stereotactic atlas was developed with an intracerebral coordinate system, as all currently available stereotactic atlases of experimental animals are based on extracranial landmarks. Advantages of the proposed method compared to the classical Horsley-Clarke method are discussed.
Experimental Pain and Transcutaneous Electrical Nerve Stimulation at High Frequency
Authors: Pertovaara A.
Published: May 2007

Transcutaneous electrical nerve stimulation (TENS) at high frequency and high intensity caused human pain threshold elevation for thermal stimuli only when thermal stimuli were applied at a site distal to the TENS electrodes. High-frequency TENS applied over the belly of m. biceps brachii did not cause a marked misestimation of elbow angle at any of the TENS intensities used. It is concluded that pain threshold elevation during high-frequency TENS is due to peripheral electrogenic blockade or fatigue of pain-mediating fibers. A minor effect of TENS on kinesthesia suggests a minor role of muscle afferents in mediating the effects of high-frequency TENS.
Cephalic and Noncephalic References in Brain Stem-Evoked Potential Recording
Authors: Rossini P.M. , Gambi D. , Marchionno L. , David P. , Sollazzo D.
Published: May 2007

55 controls were studied to investigate the morphology of brain stem-evoked potential, utilizing variable electrode arrays. In a first series the active electrodes placed at Cz and subocciput (SO) were referred to the linked earlobes. In a further 15 recording sessions, Cz, SO and A1A2 were connected to a noncephalic (hand) electrode. In the former array there was a reversed and depressed Vth wave in 95% of the cases at SO, while in the latter the peaks were phase and time-locked at all the recording sites coupled to a depressed IV-V complex from SO and A1A2 in respect to Cz.
Frequency-Dependent Phenotype Modulation of Vascular Smooth Muscle Cells under Cyclic Mechanical Strain
Authors: Qu Ming-Juan , Liu Bo , Wang Han-Qin , Yan Zhi-Qiang , Shen Bao-Rong , Jiang Zong-Lai
Published: May 2007

Phenotype transformation of vascular smooth muscle cells (VSMCs) is known to be modulated by mechanical strain. The present study was designed to investigate how different frequencies of mechanical strain affected VSMC phenotype. VSMCs were subjected to the strains of 10% elongation at 0, 0.5, 1 and 2 Hz for 24 h using a Flexercell strain unit. VSMC phenotype was assessed by cell morphology, measurement of two-dimensional cell area, Western blotting for protein and RT-PCR for mRNA expression of differentiation markers. Possible protein kinases involved were evaluated by Western blotting with their specific antibodies. The strains at certain frequencies could induce a contractile morphology in VSMC with almost perpendicular alignment to the strain direction. The strains also regulated protein and mRNA expression of several differentiation markers, as well as the activation of extracellular signal-regulated kinases (ERKs), p38 MAP kinase and protein kinase B (Akt) in a frequency-dependent manner. Furthermore, the inhibition of the p38 pathway could block the frequency-induced phenotype modulation of VSMCs, but not inhibition of ERK or Akt pathways. These results indicate that the frequency of cyclic strain can result in the differentiated phenotype of VSMCs, and it is mediated at least partly by the activation of the p38 pathway.
On the Circuits Involved in Relief of Pain and Spasticity by Posterior Column Stimulation
Authors: Spiegel E.A.
Published: May 2007

Description of the pathway probably related to relief of pain and spasticity and improvement of cerebellar function induced by stimulation of posterior column is presented.
Skin Potential and EMG Changes Induced by Cutaneous Electrical Stimulation
Authors: Francini Fabio , Zoppi Massimo , Maresca Marco , Procacci Paolo
Published: May 2007

Skin potential and EMG responses induced in normal man by electrical stimuli applied to the skin were recorded in the four limbs in order to study somato-sympathetic and somato-motor reflexes. Different patterns of responses were observed in different conditions: alarm, habituation, sensitization and arousal. During alarm, sensitization and arousal, the responses were present in the four limbs; during habituation, the responses were only present in the stimulated and in the contralateral limb. Three sensory thresholds to cutaneous electrical stimulation were identified in habituated subjects: tactile, tingling and pain. Cutaneous and EMG responses appeared at tingling threshold. A relationship between skin potential level and skin potential response was observed.
The Position and Organization of Motor Fibers in the Internal Capsule Found during Stereotactic Surgery
Authors: Hardy T.L. , Bertrand G. , Thompson C.J.
Published: May 2007

Data gathered from exploratory stimulation of the diencephalon in 130 stereotactic operative procedures have been studied, with the aid of a computer graphic technique, to show the position and topography of motor responses in the internal capsule. The results obtained indicate that pyramidal fibers are organized into a rostral-caudal face-arm-leg sequence and occupy a short compact band in the caudal third of the posterior limb of the internal capsule. This is in contrast to previous concepts of the position of these fibers in the capsule.
Relapsing Neuropathy, Cerebral Atrophy and Folate Deficiency
Authors: Botez M.I. , Peyronnard Jean-Marie , Bérubé Louise , Labrecque Raymonde
Published: May 2007

The case of a 48-year-old woman with a relapsing radial palsy which followed diarrheic episodes is reported. She had low folate concentrations in serum and cerebrospinal fluid, as well as low and borderline values of cerebrospinal fluid and erythrocyte folates. She had chronic gastrointestinal disease with edema of jejunal mucosa. The patient had some degree of cerebral atrophy. The effect of folate therapy on the neuropathy was spectacular. A beneficial effect of the therapy has been observed on both EEG tracings and neuropsychological performances after 6 months of treatment.
Nervous Reactivity Disturbances in Patients with Late Post-Traumatic Encephalic Syndromes
Authors: Rogozea R. , Florea-Ciocoiu V.
Published: May 2007

A polygraphic study performed on 184 patients with late post-traumatic encephalic syndromes has shown marked nervous reactivity disturbances. The disturbances, estimated by testing for the electrographic components of the orienting reflex elicited by a repetitive auditory stimulus and for their habituation, were expressed by alterations in the intensity, resistance to habituation and sequence of habituation of the somatic, autonomic and EEG components. The character and severity of these disturbances depended on the mechanism behind the syndrome-inducing cranio-cerebral trauma, site of the impact and clinical picture of the syndrome.
Position of the Medial Internal Capsular Border in Relation to Third-Ventricular Width
Authors: Hardy T.L. , Bertrand G. , Thompson C.J.
Published: May 2007

The position of the medial internal capsular border (lateral thalamic border) in relation to the width of the third ventricle is of considerable importance to stereotactic surgeons. Close estimation of its position from anteroposterior roentgenograms diminishes the possibility of multiple brain penetrations in an attempt to find it by electrophysiological methods. By correlating the position of the medial capsular border found by a stimulation technique, with the width of the third ventricle, in a series of 130 patients, reliable ranges of its position were obtained.
Impairments and Recovery of the Spatial and Temporal Components of a Visuomotor Pointing Movement after Unilateral Destruction of the Dentate Nucleus in the Baboon
Authors: Trouche Elisabeth , Beaubaton Daniel , Amato Giuseppe , Grangetto Arlette
Published: May 2007

In baboons trained to perform visuomotor pointing movements, unilateral electrolytic lesions are performed in the dentate nucleus. The consequences of these lesions on the following movement parameters are then studied: – temporal parameters: reaction time and movement time; – spatial parameters: pointing area and directional errors. From the observations taken 3 months after the dentate nucleus exclusion, a distinction can be made between parameters showing recovery phenomena (reaction time and pointing area) and components definitively affected (movement time and directional error).
Effect of Dorsal Column Stimulation on Pain-Induced Intracerebral Impulse Patterns
Authors: Augustinsson L.-E. , Carlsson C.-A. , Leissner P.
Published: May 2007

Evoked electrical potentials were recorded via intracerebral electrodes in a patient with stump and phantom limb pain who had a previously implanted dorsal column stimulator. When pain was elicited by peripheral stimulation it was found that positive deflections appeared in the ventrolateral nucleus of the thalamus at time latencies corresponding to the propagation velocities of Aδ- and C-fibres. Dorsal column stimulation completely eliminated the C-fibre deflection and partially eliminated the Aδ-fibre deflection.
Postural Dependence of Reaction Time after a VL Thalamotomy
Authors: Nakamura Ryuichi , Taniguchi Reiji , Narabayashi Hirotaro , Yokochi Fusako
Published: May 2007

Postural dependence of the EMG-RT of the triceps brachii muscles was measured in 68 parkinsonian patients of which 38 underwent a ventrolateral thalamotomy. A thalamotomy did not affect patients’ EMG-RT per se, but it changed the postural dependence of the EMG-RT. After left thalamotomy the position changes of both shoulders did not influence the EMG-RT of the right triceps, and after right thalamotomy the position change of the left shoulder had no influence on the EMG-RT of both triceps. As for the sensorimotor function, it is assumed that the right thalamus has bilateral control on the input system and the left thalamus has bilateral control on the output system.
Organization and Topography of Sensory Responses in the Internal Capsule and Nucleus Ventralis Caudalis Found During Stereotactic Surgery
Authors: Hardy Tyrone L. , Bertrand Gilles , Thompson C.J.
Published: May 2007

With the aid of a computer graphic technique, data gathered from exploratory stimulation of the diencephalon in 130 stereotactic operative procedures indicate that some sensory fibers in the capsule are parallel to motor fibers at basal thalamic levels and occupy a position medial to motor fibers. In addition, stimulus responses which probably represent thalamocortical projections from S II somesthetic thalamus were found to lie in a capsular zone rostral to the motor bundle. The organization of S I somesthetic thalamus was found to agree with the previous findings of Tasker et al. and some of these fibers project within the motor bundle to cortical motor areas.
Further Observations on the Syndrome of Chronic Encephalitis and Epilepsy
Authors: Rasmussen Theodore
Published: May 2007

This report is a sequel to our 1958, 1960 and 1968 reports on a series of patients operated upon for focal epilepsy whose surgical specimens unexpectedly showed histological lesions typical of active encephalitis. None of these patients, now 27 in number, exhibited the clinical picture ordinarily associated with encephalitis. With one exception, all showed a severe focal seizure tendency beginning in infancy or childhood, often associated with episodes of epilepsia partialis continua. In addition, all except 2 showed slowly progressive neurological deterioration, usually hemiparesis and mental retardation, which advanced over periods of months or years before the progression became arrested. No infectious agent has yet been identified by standard viral studies carried out in the most recent 14 patients or by investigation for slow viruses in 6 patients operated upon between 1966 and 1971. The clinical course of this condition is outlined and the role, the timing and the results of treatment by craniotomy and cortical excision are discussed.
Temporal Lobe Seizures and Hypersexuality
Authors: Andy Orlando J. , Velamati Sudha
Published: May 2007

Postictal hypersexuality was induced in 9 male adult cats by repeated stimulation and discharges in limbic and basal ganglia structures.
Discussion on the Causes of Failure of Surgical Treatment of Partial Epilepsies
Authors: Rossi Gian Franco , Colicchio Gabriella , Gentilomo Adriano , Scerrati Massimo
Published: May 2007

Despite continuous improvement in diagnosis and surgery, persistence of seizures following surgical treatment of partial epilepsies still occurs in a relevant number of cases (30–40%). The analysis of personal material and of data from the literature appears to indicate that relevant causes of surgical failure are difficulties in delimitation of the epileptogenic zone and therefore of complete surgical removal. These difficulties are illustrated and discussed.
Surprise Finding 5 Years after Stereotactic Amygdalotomy
Authors: Nittner K.
Published: May 2007

Before extinction of an epileptogenic focus exclusion of an intracranial tumor or an angioma by EEG, isotope and contrast medium diagnosis must be attempted. A case history is presented of a patient in whom a malignant glioma was discovered 5 years after stereotactic treatment for epilepsy.