bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats
Authors: Sills Robert C. , Morgan Daniel L. , Herr David W. , Little Peter B. , George Nneka M. , Thai Vu Ton  , Love Nancy E. , Maronpot Robert R. , Johnson G. Allan
Published: July 2004

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200—600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.
Two Cases of Adreno-Hepatic Fusion in Cynomolgus Monkeys (Macaca fascicularis)
Authors: Mousa Sien , Van Esch Eric
Published: July 2004

In this report we describe 2 cases of adreno-hepatic fusion (AHF) in Cynomolgus monkeys ( Macaca fascicularis ) used in short-term toxicity studies. AHF is defined as the union of hepatic tissue with the adrenal gland with close intermingling of the respective parenchymal cells. In this condition, a continuous intervening connective tissue septum is lacking. AHF is believed to be a congenital anomaly caused by a defect or delay in the formation of the organ capsules from the intermediate primitive mesenchymal stroma. To our knowledge, this is the first time this anomaly is described in the monkey.
Regulation of K+ Flow by a Ring of Negative Charges in the Outer Pore of BKCa Channels. Part I
Authors: Haug Trude , Sigg Daniel , Ciani Sergio , Toro Ligia , Stefani Enrico , Olcese Riccardo
Published: July 2004

The pore region of the majority of K+ channels contains the highly conserved GYGD sequence, known as the K+ channel signature sequence, where the GYG is critical for K+ selectivity (Heginbotham, L., T. Abramson, and R. MacKinnon. 1992. Science. 258:1152–1155). Exchanging the aspartate residue with asparagine in this sequence abolishes ionic conductance of the Shaker K+ channel (D447N) (Hurst, R.S., L. Toro, and E. Stefani. 1996. FEBS Lett. 388:59–65). In contrast, we found that the corresponding mutation (D292N) in the pore forming α subunit (hSlo) of the voltage- and Ca2+-activated K+ channel (BKCa, MaxiK) did not prevent conduction but reduced single channel conductance. We have investigated the role of outer pore negative charges in ion conduction (this paper) and channel gating (Haug, T., R. Olcese, T. Ligia, and E. Stefani. 2004. J. Gen Physiol. 124:185–197). In symmetrical 120 mM [K+], the D292N mutation reduced the outward single channel conductance by ∼40% and nearly abolished inward K+ flow (outward rectification). This rectification was partially relieved by increasing the external K+ concentration to 700 mM. Small inward currents were resolved by introducing an additional mutation (R207Q) that greatly increases the open probability of the channel. A four-state multi-ion pore model that incorporates the effects of surface charge was used to simulate the essential properties of channel conduction. The conduction properties of the mutant channel (D292N) could be predicted by a simple ∼8.5-fold reduction of the surface charge density without altering any other parameter. These results indicate that the aspartate residue in the BKCa pore plays a key role in conduction and suggest that the pore structure is not affected by the mutation. We speculate that the negative charge strongly accumulates K+ in the outer vestibule close to the selectivity filter, thus increasing the rate of ion entry into the pore.
Regulation of K+ Flow by a Ring of Negative Charges in the Outer Pore of BKCa Channels. Part II
Authors: Haug Trude , Olcese Riccardo , Toro Ligia , Stefani Enrico
Published: July 2004

Neutralization of the aspartate near the selectivity filter in the GYGD pore sequence (D292N) of the voltage- and Ca2+-activated K+ channel (MaxiK, BKCa) does not prevent conduction like the corresponding mutation in Shaker channel, but profoundly affects major biophysical properties of the channel (Haug, T., D. Sigg, S. Ciani, L. Toro, E. Stefani, and R. Olcese. 2004. J. Gen. Physiol. 124:173–184). Upon depolarizations, the D292N mutant elicited mostly gating current, followed by small or no ionic current, at voltages where the wild-type hSlo channel displayed robust ionic current. In fact, while the voltage dependence of the gating current was not significantly affected by the mutation, the overall activation curve was shifted by ∼20 mV toward more depolarized potentials. Several lines of evidence suggest that the mutation prevents population of certain open states that in the wild type lead to high open probability. The activation curves of WT and D292N can both be fitted to the sum of two Boltzmann distributions with identical slope factors and half activation potentials, just by changing their relative amplitudes. The steeper and more negative component of the activation curve was drastically reduced by the D292N mutation (from 0.65 to 0.30), suggesting that the population of open states that occurs early in the activation pathway is reduced. Furthermore, the slow component of the gating current, which has been suggested to reflect transitions from closed to open states, was greatly reduced in D292N channels. The D292N mutation also affected the limiting open probability: at 0 mV, the limiting open probability dropped from ∼0.5 for the wild-type channel to 0.06 in D292N (in 1 mM [Ca2+]i). In addition to these effects on gating charge and open probability, as already described in Part I, the D292N mutation introduces a ∼40% reduction of outward single channel conductance, as well as a strong outward rectification.
Revisiting the Role of H+ in Chemotactic Signaling of Sperm
Authors: Solzin Johannes , Helbig Annika , Van Qui , Brown Joel E. , Hildebrand Eilo , Weyand Ingo , Kaupp U. Benjamin
Published: July 2004

Chemotaxis of sperm is an important step toward fertilization. During chemotaxis, sperm change their swimming behavior in a gradient of the chemoattractant that is released by the eggs, and finally sperm accumulate near the eggs. A well established model to study chemotaxis is the sea urchin Arbacia punctulata. Resact, the chemoattractant of Arbacia, is a peptide that binds to a receptor guanylyl cyclase. The signaling pathway underlying chemotaxis is still poorly understood. Stimulation of sperm with resact induces a variety of cellular events, including a rise in intracellular pH (pHi) and an influx of Ca2+; the Ca2+ entry is essential for the chemotactic behavior. Previous studies proposed that the influx of Ca2+ is initiated by the rise in pHi. According to this proposal, a cGMP-induced hyperpolarization activates a voltage-dependent Na+/H+ exchanger that expels H+ from the cell. Because some aspects of the proposed signaling pathway are inconsistent with recent results (Kaupp, U.B., J. Solzin, J.E. Brown, A. Helbig, V. Hagen, M. Beyermann, E. Hildebrand, and I. Weyand. 2003. Nat. Cell Biol. 5:109–117), we reexamined the role of protons in chemotaxis of sperm using kinetic measurements of the changes in pHi and intracellular Ca2+ concentration. We show that for physiological concentrations of resact (<25 pM), the influx of Ca2+ precedes the rise in pHi. Moreover, buffering of pHi completely abolishes the resact-induced pHi signal, but leaves the Ca2+ signal and the chemotactic motor response unaffected. We conclude that an elevation of pHi is required neither to open Ca2+-permeable channels nor to control the chemotactic behavior. Intracellular release of cGMP from a caged compound does not cause an increase in pHi, indicating that the rise in pHi is induced by cellular events unrelated to cGMP itself, but probably triggered by the consumption and subsequent replenishment of GTP. These results show that the resact-induced rise in pHi is not an obligatory step in sperm chemotactic signaling. A rise in pHi is also not required for peptide-induced Ca2+ entry into sperm of the sea urchin Strongylocentrotus purpuratus. Speract, a peptide of S. purpuratus may act as a chemoattractant as well or may serve functions other than chemotaxis.
Can Shaker Potassium Channels be Locked in the Deactivated State?
Authors: Yang Youshan , Yan Yangyang , Sigworth Fred J.
Published: July 2004

For structural studies it would be useful to constrain the voltage sensor of a voltage-gated channel in its deactivated state. Here we consider one Shaker potassium channel mutant and speculate about others that might allow the channel to remain deactivated at zero membrane potential. Ionic and gating currents of F370C Shaker, expressed in Xenopus oocytes, were recorded in patches with internal application of the methanethiosulfonate reagent MTSET. It appears that the voltage dependence of voltage sensor movement is strongly shifted by reaction with internal MTSET, such that the voltage sensors appear to remain deactivated even at positive potentials. A disadvantage of this construct is that the rate of modification of voltage sensors by MTSET is quite low, ∼0.17 mM−1·s−1 at −80 mV, and is expected to be much lower at depolarized potentials.
Discovery of Glycine Hydrazide Pore-occluding CFTR Inhibitors
Authors: Muanprasat Chatchai , Sonawane N.D. , Salinas Danieli , Taddei Alessandro , Galietta Luis J.V. , Verkman A.S.
Published: July 2004

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated epithelial Cl− channel that, when defective, causes cystic fibrosis. Screening of a collection of 100,000 diverse small molecules revealed four novel chemical classes of CFTR inhibitors with Ki < 10 μM, one of which (glycine hydrazides) had many active structural analogues. Analysis of a series of synthesized glycine hydrazide analogues revealed maximal inhibitory potency for N-(2-naphthalenyl) and 3,5-dibromo-2,4-dihydroxyphenyl substituents. The compound N-(2-naphthalenyl)-[(3,5-dibromo-2,4-dihydroxyphenyl)methylene]glycine hydrazide (GlyH-101) reversibly inhibited CFTR Cl− conductance in <1 min. Whole-cell current measurements revealed voltage-dependent CFTR block by GlyH-101 with strong inward rectification, producing an increase in apparent inhibitory constant Ki from 1.4 μM at +60 mV to 5.6 μM at −60 mV. Apparent potency was reduced by lowering extracellular Cl− concentration. Patch-clamp experiments indicated fast channel closures within bursts of channel openings, reducing mean channel open time from 264 to 13 ms (−60 mV holding potential, 5 μM GlyH-101). GlyH-101 inhibitory potency was independent of pH from 6.5–8.0, where it exists predominantly as a monovalent anion with solubility ∼1 mM in water. Topical GlyH-101 (10 μM) in mice rapidly and reversibly inhibited forskolin-induced hyperpolarization in nasal potential differences. In a closed-loop model of cholera, intraluminal GlyH-101 (2.5 μg) reduced by ∼80% cholera toxin–induced intestinal fluid secretion. Compared with the thiazolidinone CFTR inhibitor CFTRinh-172, GlyH-101 has substantially greater water solubility and rapidity of action, and a novel inhibition mechanism involving occlusion near the external pore entrance. Glycine hydrazides may be useful as probes of CFTR pore structure, in creating animal models of CF, and as antidiarrheals in enterotoxic-mediated secretory diarrheas.
Toll-Like Receptor 4 (TLR4) of Retinal Pigment Epithelial Cells Participates in Transmembrane Signaling in Response to Photoreceptor Outer Segments
Authors: Kindzelskii Andrei L. , Elner Victor M. , Elner Susan G. , Yang Dongli , Hughes Bret A. , Petty Howard R.
Published: July 2004

Retinal pigment epithelial (RPE) cells mediate the recognition and clearance of effete photoreceptor outer segments (POS), a process central to the maintenance of normal vision. Given the emerging importance of Toll-like receptors (TLRs) in transmembrane signaling in response to invading pathogens as well as endogenous substances, we hypothesized that TLRs are associated with RPE cell management of POS. TLR4 clusters on human RPE cells in response to human, but not bovine, POS. However, TLR4 clustering could be inhibited by saturating concentrations of an inhibitory anti-TLR4 mAb. Furthermore, human POS binding to human RPE cells elicited transmembrane metabolic and calcium signals within RPE cells, which could be blocked by saturating doses of an inhibitory anti-TLR4 mAb. However, the heterologous combination of bovine POS and human RPE did not trigger these signals. The pattern recognition receptor CD36 collected at the POS–RPE cell interface for both homologous and heterologous samples, but human TLR4 only collected at the human POS–human RPE cell interface. Kinetic experiments of human POS binding to human RPE cells revealed that CD36 arrives at the POS–RPE interface followed by TLR4 accumulation within 2 min. Metabolic and calcium signals immediately follow. Similarly, the production of reactive oxygen metabolites (ROMs) was observed for the homologous human system, but not the heterologous bovine POS–human RPE cell system. As (a) the bovine POS/human RPE combination did not elicit TLR4 accumulation, RPE signaling, or ROM release, (b) TLR4 arrives at the POS–RPE cell interface just before signaling, (c) TLR4 blockade with an inhibitory anti-TLR4 mAb inhibited TLR4 clustering, signaling, and ROM release in the human POS–human RPE system, and (d) TLR4 demonstrates similar clustering and signaling responses to POS in confluent RPE monolayers, we suggest that TLR4 of RPE cells participates in transmembrane signaling events that contribute to the management of human POS.
Gating Transitions in Bacterial Ion Channels Measured at 3 μs Resolution
Authors: Shapovalov George , Lester Henry A.
Published: July 2004

Ion channels of high conductance (>200 pS) are widespread among prokaryotes and eukaryotes. Two examples, the Escherichia coli mechanosensitive ion channels Ec-MscS and Ec-MscL, pass currents of 125–300 pA. To resolve temporal details of conductance transitions, a patch-clamp setup was optimized for low-noise recordings at a time resolution of 3 μs (10–20 times faster than usual). Analyses of the high-resolution recordings confirm that Ec-MscL visits many subconductance states and show that most of the intersubstate transitions occur more slowly than the effective resolution of 3 μs. There is a clear trend toward longer transition times for the larger transitions. In Ec-MscS recordings, the majority of the observed full conductance transitions are also composite. We detected a short-lived (∼20 μs) Ec-MscS substate at 2/3 of full conductance; transitions between 2/3 and full conductance did not show fine structure and had a time course limited by the achieved resolution. Opening and closing transitions in MscS are symmetrical and are not preceded or followed by smaller, rapid currents (“anticipations” or “regrets”). Compared with other, lower-conductance channels, these measurements may detect unusually early states in the transitions from fully closed to fully open. Increased temporal resolution at the single-molecule level reveals that some elementary steps of structural transitions are composite and follow several alternative pathways, while others still escape resolution. High-bandwidth, low-noise single-channel measurements may provide details about state transitions in other high-conductance channels; and similar procedures may also be applied to channel- and nanopore-based single-molecule DNA measurements.
Effect of Hochu‐ekki‐to (TJ‐41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome
Authors: Wang Xin Q. , Takahashi Takashi , Zhu Shi-jie , Moriya Junji , Saegusa Seiichiro , Yamakawa Jun′ichi , Kusaka Kazuya , Itoh Tohru , Kanda Tsugiyasu
Published: August 2004

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu‐ekki‐to (TJ‐41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ‐41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ‐41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin‐10 (IL‐10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ‐41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL‐10 mRNA levels were observed in the spleens of the mice treated with TJ‐41. Our data suggest that Hochu‐ekki‐to might possess an inhibitory effect on the marked decrease in running activity following BA injection.
Spontaneous Intracranial Hypotension Mimicking Aneurysmal Subarachnoid Hemorrhage
Authors: Schievink Wouter I. , Wijdicks Eelco F.M. , Meyer Fredric B. , Sonntag Volker K.H.
Published: July 2004

OBJECTIVE

An excruciating headache of instantaneous onset is known as a thunderclap headache. A subarachnoid hemorrhage is the prototypical cause, but other serious disorders may also present with a thunderclap headache, including cerebral venous sinus thrombosis, carotid artery dissection, and pituitary apoplexy. We report a group of patients with thunderclap headaches as the initial manifestation of spontaneous intracranial hypotension caused by a spinal cerebrospinal fluid leak.

METHODS

Among 28 patients with spontaneous intracranial hypotension due to a documented spinal cerebrospinal fluid leak, four (14%) initially experienced an excruciating headaches of instantaneous onset.

RESULTS

The mean age of the four patients (two men and two women) was 35 years (range, 24–45 yr). Nuchal rigidity was present in the three patients who sought early medical attention, and they underwent emergency computed tomographic scanning, lumbar puncture, and cerebral angiography to rule out an aneurysmal subarachnoid hemorrhage. The delay between the onset of headache and diagnosis of intracranial hypotension ranged from 4 days to 5 weeks. A fourth patient did not seek medical attention until 1 month after the ictus.

CONCLUSION

Spontaneous intracranial hypotension should be included in the differential diagnosis of thunderclap headache, even when meningismus is present.
Spontaneous Intraparenchymal Hemorrhage in Full-term Neonates
Authors: Sandberg David I. , Lamberti-Pasculli Maria , Drake James M. , Humphreys Robin P. , Rutka James T.
Published: July 2004

OBJECTIVE

Spontaneous intraparenchymal hemorrhage is extremely rare in full-term newborns. Reports to date have been limited to descriptions of individual cases, small groups within larger studies of intracranial hemorrhage, and one series of four patients. Structural lesions are rarely identified, and the majority of patients described have been managed without surgical intervention.

METHODS

Analysis of a computerized database of pediatric neurosurgical patients from January 1960 to February 2000 identified full-term newborns younger than 3 months of age with nontraumatic intraparenchymal hemorrhages. Prenatal histories, labor and delivery histories, clinical presentations, imaging studies, management, and outcomes were reviewed.

RESULTS

Eleven full-term newborns with spontaneous intraparenchymal hemorrhages were identified. The majority had normal prenatal courses. Most presented within the first 2 days of life (6 of 11 patients), and the most common presenting sign was seizure (7 of 11 patients). No cause was identified in 6 of 11 patients; the remainder were attributed to coagulopathy (n = 3), ruptured intracranial aneurysm (n = 1), or hemorrhagic infarction (n = 1). Eight patients underwent surgical hematoma evacuation on the basis of radiographic evidence of significant mass effect, evidence of signs of elevated intracranial pressure, or both. Three patients did not receive surgical intervention. There were no subsequent hemorrhages or deaths during a mean follow-up period of 4.5 years (range, 1–16 yr). Four patients had normal neurological outcomes, four had motor deficits (one of whom additionally demonstrated cognitive delay), and three had delayed speech.

CONCLUSION

No cause is identified in most newborns with spontaneous intraparenchymal hemorrhage. Radiographic evidence of mass effect or signs of elevated intracranial pressure may necessitate surgical hematoma evacuation. Outcome varies widely and may be normal, even in patients with sizeable intraparenchymal hemorrhages.
Are Nonfunctioning Pituitary Adenomas Extending into the Cavernous Sinus Aggressive and/or Invasive?
Authors: Yokoyama Shunichi , Hirano Hirofumi , Moroki Koichi , Goto Masamichi , Imamura Shinichi , Kuratsu Jun-ichi
Published: July 2004

OBJECTIVE

We studied nonfunctioning pituitary adenomas extending to the cavernous sinus to gain insight into the discrepancy between their histologically benign nature and frequent extension into the cavernous sinus.

METHODS

We studied 10 patients with nonfunctioning pituitary adenomas that completely encircled the cavernous carotid artery (extension group). All 10 patients underwent surgery to remove intrasellar and/or suprasellar parts of the adenomas. Ten patients with nonfunctioning pituitary adenomas without cavernous sinus extension comprised the control group. Tumor size follow-up data were obtained by magnetic resonance imaging. Immunostaining was performed for Ki-67, cathepsin B, and matrix metalloprotainase-9. To assess the wall thickness, 10 cavernous sinuses were removed from the cranial base of adult cadavers, and the walls were examined histologically.

RESULTS

Magnetic resonance imaging demonstrated no remarkable growth in most of the patients during the follow-up period (mean, 65.8 mo). There was no statistical difference in Ki-67, cathepsin B, and matrix metalloprotainase-9 immunostaining between the extension group and the control group. The cadaver study demonstrated that the medial wall was significantly thinner than the superior and the lateral walls (P < 0.0005). We found small defects in the capsule histologically in 3 of 30 sections.

CONCLUSION

Our results indicate that most of nonfunctioning pituitary adenomas extending into the cavernous sinus are neither aggressive nor invasive. The high incidence of cavernous sinus extension of benign adenomas may be caused by the weakness of the medial wall of the cavernous sinus.
Management Strategy for Adult Patients with Dorsal Midbrain Gliomas
Authors: Yeh David D. , Warnick Ronald E. , Ernst Robert J.
Published: July 2004

OBJECTIVE:

Dorsal midbrain gliomas (DMGs) involving the tectum occur more commonly in children than in adults. These lesions are often indolent in nature, and patients require treatment only for obstructive hydrocephalus. Because limited information is available concerning adults with this type of lesion, we describe our experience and management strategy in adults with DMGs.

METHODS:

We retrospectively reviewed the charts and magnetic resonance imaging scans of five adult patients (four men, one woman; mean age, 51.6 yr; range, 23–69 yr) who were treated from March 1992 to August 2001 for DMGs involving the tectum. The mean follow-up time for these patients was 71.4 months (range, 25–113 mo). We analyzed the data to determine the optimal treatment strategy and outcomes of patients with DMGs. Tumor volume was analyzed objectively with Scion Image software (Scion Corp., Frederick, MD) to document changes in volume and determine whether treatment strategy differed significantly with tumor size.

RESULTS:

Tumors in two of these patients were found incidentally, and three others presented with obstructive hydrocephalus. Magnetic resonance imaging scans demonstrated an isolated tectal glioma in one patient, tectal and tegmental (periaqueductal) gliomas in three patients, and a tectal glioma with right thalamic extension in one patient. Treatment consisted of routine follow-up for the two asymptomatic patients and cerebrospinal fluid diversion surgery for the three patients with hydrocephalus. Volumetric analysis demonstrated that all asymptomatic patients had tumors smaller than 9.3 cm3, and symptomatic patients had tumors larger than 28.5 cm3. All follow-up magnetic resonance imaging scans revealed stable dorsal midbrain lesions, and no patient required tumor-specific therapy.

CONCLUSION:

Although tumors of the dorsal midbrain occur primarily in the pediatric population, similar tumors may occur in adults. As has been learned from experience with children, these lesions are often clinically and radiographically stable and require only appropriate therapy for obstructive hydrocephalus. We advocate a similar conservative strategy of routine imaging follow-up and treatment for hydrocephalus in adult patients. Surgery and other therapy should be reserved for patients with progressive lesions.
Meningovenous Structures of the Petroclival Region: Clinical Importance for Surgery and Intravascular Surgery
Authors: Ozveren Mehmet Faik , Uchida Koichi , Aiso Sadakazu , Kawase Takeshi
Published: July 2004

OBJECTIVE:

The goals of this investigation were to perform a detailed analysis of petroclival microanatomic features, to investigate the course of the abducens nerve in the petroclival region, and to identify potential causes of injury to neurovascular structures when anterior transpetrosal or transvenous endovascular approaches are used to treat pathological lesions in the petroclival region.

METHODS:

Petroclival microanatomic features were studied bilaterally in seven cadaveric head specimens, which were injected with colored silicone before microdissection. Another cadaveric head was used for histological section analyses.

RESULTS:

A lateral or medial location of the abducens nerve dural entrance porus, relative to the midline, was correlated with the course and angulation of the abducens nerve in the petroclival region. The angulation of the abducens nerve was greater and the nerve was closer to the petrous ridge in the lateral type, compared with the medial type. The abducens nerve exhibited three changes in direction, which represented the angulations in the petroclival region, at the dural entrance porus, the petrous apex, and the lateral wall of the internal carotid artery. The abducens nerve was covered by the dural sleeve and the arachnoid membrane, which became attenuated between the second and third angulation points. The abducens nerve was anastomosed with the sympathetic plexus and fixed by connective tissue extensions to the lateral wall of the internal carotid artery and the medial wall of Meckel's cave at the third angulation point. There were two types of trabeculations inside the sinuses around the petroclival region (tough and delicate).

CONCLUSION:

The petroclival part of the abducens nerve was protected in a dural sleeve accompanied by the arachnoid membrane. Therefore, the risk of abducens nerve injury during petrous apex resection via the anterior transpetrosal approach, with the use of the transvenous route through the inferior petrosal sinus to the cavernous sinus, should be lower than expected. The presence of two anatomic variations in the course of the abducens nerve, in addition to findings regarding nerve angulation and tethering points, may explain the relationships between adjacent structures and the susceptibility to nerve injury with either surgical or endovascular approaches. Venous anatomic variations may account for previously reported cases of subarachnoid hemorrhage with the endovascular approach.
Magnetic Resonance Imaging-guided Stereotactic Limbic Leukotomy for Treatment of Intractable Psychiatric Disease
Authors: Montoya Alonso , Weiss Anthony P. , Price Bruce H. , Cassem Edwin H. , Dougherty Darin D. , Nierenberg Andrew A. , Rauch Scott L. , Cosgrove G. Rees
Published: July 2004

OBJECTIVE:

To assess the efficacy and complication rates of magnetic resonance imaging-guided stereotactic limbic leukotomy for the treatment of intractable major depressive disorder (MDD) and obsessive-compulsive disorder (OCD).

METHODS:

We conducted preoperative evaluations and postoperative follow-up assessments of efficacy and complications for 21 patients who underwent limbic leukotomy. Efficacy was based on physician- and patient-rated global assessments of functioning, as well as evaluations using disease-specific rating scales commonly used in studies of MDD and OCD.

RESULTS:

The mean time from limbic leukotomy to follow-up assessment was 26 months. On the basis of standard outcome measures, 36 to 50% of patients were considered to be treatment responders. Although permanent surgical morbidity was rare, there were reports of postoperative sequelae, including apathy, urinary incontinence, and memory complaints, which occurred in a substantial minority of cases.

CONCLUSION:

For this cohort of 21 patients with chronic severe MDD or OCD, who had experienced failure with an exhaustive array of previous treatments, limbic leukotomy was associated with substantial benefit for 36 to 50%. This rate is comparable to those of previous studies of limbic system surgery and indicates that limbic leukotomy is a feasible treatment option for severe, treatment-refractory MDD or OCD. Adverse consequences associated with the procedure included affective, cognitive, and visceromotor sequelae, which were generally transient.
Trans-supraorbital Approach to Supratentorial Aneurysms
Authors: Ramos-Zúñiga Rodrigo , Velázquez Héctor , Barajas Marco A. , López Ramiro , Sánchez Enrique , Trejo Sandra
Published: July 2004

OBJECTIVE

The trans-supraorbital approach has the advantage of combining the keyhole principle with cranial base surgery. The anatomic fields that can be visualized with the use of this procedure have been demonstrated in cadavers, and the advantages and potential surgical applications of this procedure are described in this report. This article is the first to describe a group of intracranial supratentorial aneurysms.

METHODS

We used the trans-supraorbital approach in 22 cases of supratentorial aneurysms. In this technique, an incision is made through the eyebrow, then a 3.5-cm craniotomy is performed with en bloc extension to the orbital arch, complemented by different drilling extensions of the orbital roof according to the surgical objective. We describe the anatomic details of the experimental work as well as the clinical results.

RESULTS

The trans-supraorbital technique offers an unlimited wide exposure of neurovascular structures in this microsurgical corridor. The craniotomy extension allows greater exposure than the conventional keyhole supraorbital approach, which makes the technique safe for the patient and comfortable for the surgeon. All patient outcomes were successful; no serious complications from the surgical technique occurred. Our success was achieved through better microscopic illumination in the deep field and by gaining access to the complete supratentorial vascular territory with minimal cerebral retraction and an acceptable cosmetic result.

CONCLUSION

The trans-supraorbital approach is effective for gaining access to and treating supratentorial aneurysms. Also, the microsurgical field is more convenient in microscope-assisted surgery because total reliance on the endoscope is not required, and minimal brain retraction is needed. This modification of the keyhole procedure also provides multiple surgical options in this microsurgical corridor, using the principles of minimal invasiveness in cranial base surgery.
Quantum chemical studies of protein structure
Authors: Oldfield Eric
Published: July 2004

Quantum chemical methods now permit the prediction of many spectroscopic observables in proteins and related model systems, in addition to electrostatic properties, which are found to be in excellent accord with those determined from experiment. I discuss the developments over the past decade in these areas, including predictions of nuclear magnetic resonance chemical shifts, chemical shielding tensors, scalar couplings and hyperfine (contact) shifts, the isomer shifts and quadrupole splittings in Mössbauer spectroscopy, molecular energies and conformations, as well as a range of electrostatic properties, such as charge densities, the curvatures, Laplacians and Hessians of the charge density, electrostatic potentials, electric field gradients and electrostatic field effects. The availability of structure/spectroscopic correlations from quantum chemistry provides a basis for using numerous spectroscopic observables in determining aspects of protein structure, in determining electrostatic properties which are not readily accessible from experiment, as well as giving additional confidence in the use of these techniques to investigate questions about chemical bonding and chemical reactions.
In the pink: Homosexual‐heterosexual wage differentials in the UK
Authors: Reza Arabsheibani G. , Marin Alan , Wadsworth Jonathan
Published: August 2004

There are few systematic studies of wage discrimination against homosexuals: none for the UK. This paper studies the earnings of homosexual men and women in the UK relative to their heterosexual counterparts. Homosexuals are identified as individuals living with “same sex partners”. Although gays of either sex earn more than non‐gays, once allowance is made for differences in characteristics gay men appear to be paid less than heterosexuals, while lesbians appear to be paid more. As this implies, the gender pay gap is smaller amongst homosexuals than amongst heterosexuals. The gay male pay penalty is significantly lower in London than elsewhere.
North/South infrastructure development via cross‐border PPP mechanisms
Authors: Henderson Joan , McGloin Eileen
Published: August 2004

Both Northern Ireland and Republic of Ireland governments recognise the current infrastructural deficits in their respective jurisdictions which, if not addressed, will undermine the future economic prosperity of both regions. This paper considers the adoption of a collaborative approach on the island to addressing the deficit, using public private partnerships (PPP) as the delivery vehicle. It presents a critical perspective of the challenges and opportunities posed by adopting such a cross‐border approach. Whilst PPPs have the potential to bring about North‐South co‐operation, bridge gaps in infrastructure capacity and facilitate the advancement of sectoral knowledge, their adoption on a cross border basis will require significant reorganisation and change at administrative and sectoral levels. This review concludes that governments and construction sector representatives in Northern Ireland and the Republic of Ireland have still some work to do in order to enhance the capability and readiness of public and private partners to evolve an all‐island PPP infrastructure development approach.
Both chaperone and isomerase functions of protein disulfide isomerase are essential for acceleration of the oxidative refolding and reactivation of dimeric alkaline protease inhibitor
Authors: Pandhare Jui , Deshpande Vasanti
Published: August 2004

Oxidative refolding of the dimeric alkaline protease inhibitor (API) from Streptomyces sp. NCIM 5127 has been investigated. We demonstrate here that both isomerase and chaperone functions of the protein folding catalyst, protein disulfide isomerase (PDI), are essential for efficient refolding of denatured‐reduced API (dr‐API). Although the role of PDI as an isomerase and a chaperone has been reported for a few monomeric proteins, its role as a foldase in refolding of oligomeric proteins has not been demonstrated hitherto. Spontaneous refolding and reactivation of dr‐API in redox buffer resulted in 45% to 50% reactivation. At concentrations <0.25 μM, reactivation rates and yields of dr‐API are accelerated by catalytic amounts of PDI through its isomerase activity, which promotes disulfide bond formation and rearrangement. dr‐API is susceptible to aggregation at concentrations >25 μM, and a large molar excess of PDI is required to enhance reactivation yields. PDI functions as a chaperone by suppressing aggregation and maintains the partially unfolded monomers in a folding‐competent state, thereby assisting dimerization. Simultaneously, isomerase function of PDI brings about regeneration of native disulfides. 5‐Iodoacetamidofluorescein–labeled PDI devoid of isomerase activity failed to enhance the reactivation of dr‐API despite its intact chaperone activity. Our results on the requirement of a stoichiometric excess of PDI and of presence of PDI in redox buffer right from the initiation of refolding corroborate that both the functions of PDI are essential for efficient reassociation, refolding, and reactivation of dr‐API.
Insulin amyloid fibrillation at above 100°C: New insights into protein folding under extreme temperatures
Authors: Arora Anubhav , Ha Chanki , Park Chan Beum
Published: August 2004

To investigate the folding behavior of amyloidogenic proteins under extreme temperatures, the kinetics of fibrillation and accompanying secondary structure transitions of bovine insulin were studied for temperatures ranging up to 140°C. The presence of extreme heat stress had traditionally been associated with irreversible denaturation of protein while the initial steps of such a denaturation process may be common with a fibril formation pathway of amyloidogenic proteins. The present work demonstrates the ability of insulin to form amyloid fibrils at above 100°C. Amyloid formation was gradually replaced by random coil generation after ∼80°C until no amyloid was detected at 140°C. The morphology of insulin amyloid fibrils underwent sharp changes with increasing the temperature. The dependence of amyloid formation rate on incubation temperature followed non‐Arrhenius kinetics, which is explained by temperature‐dependent enthalpy change for amyloid formation. The intermediate stage of amyloid formation and random coil generation consisted of a partially folded intermediate common to both pathways. The fully unfolded monomers in random coil conformation showed partial reversibility through this intermediate by reverting back to the amyloid pathway when formed at 140°C and incubated at 100°C. This study highlights the non‐Arrhenius kinetics of amyloid fibrillation under extreme temperatures, and elucidates its intermediate stage common with random coil formation.
Changes in wheat root enzymes correlated with resistance to cereal cyst nematodes
Authors: Andres M. F. , Melillo M. T. , Delibes A. , Romero M. D. , Bleve‐Zacheo T.
Published: July 2004

The response of the resistant wheat/Aegilops ventricosa introgression line, H‐93‐8, to a Spanish population of the cereal cyst nematode, Heterodera avenae, was studied in order to determine changes in gene expression correlated with resistance.

Roots of susceptible (Triticum aestivum cv. Anza) and resistant wheat seedlings were analysed using histological (electron microscopy), cytochemical (at tissue and cytological level) and biochemical (isoelectrofocusing) techniques.

Infection of resistant wheat lines with H. avenae resulted in a hypersensitive reaction, with syncytial cells deteriorating in a few days. Following nematode infection, peroxidase, esterase and superoxide dismutase activities were increased in H‐93‐8 roots compared with the susceptible wheat. Syncytial cells in roots of resistant lines were highly reactive to diaminobenzidine and homovanillic acid oxidase, the latter associated with plasma and nuclear membranes and vacuoles. The same syncytial cells showed early positive reaction to phloroglucinol, indicating lignification.

The Cre2 resistance gene in H‐93‐8 inhibited reproduction of H. avenae. Peroxidases, esterases and superoxide dismutase might represent products of genes whose expression is correlated with the resistance response to this nematode.
Epoxy‐based production of wind turbine rotor blades: occupational dermatoses
Authors: Pontén A. , Carstensen O. , Rasmussen K. , Gruvberger B. , Isaksson M. , Bruze M.
Published: July 2004

Occupational dermatoses were investigated in a factory producing rotor blades for wind turbines by an epoxy‐based process. In a blinded study design, 603 workers were first interviewed and thereafter clinically examined. Based on a history of work‐related skin disease, clinical findings of dermatitis, or both, 325 (53.9%) of the workers were patch tested with a specially profiled occupational patch‐test series and the European standard patch‐test series. Calculated on all investigated workers, 17.1% of the workers were diagnosed with occupational dermatoses caused by work. Occupational allergic contact dermatitis was found in 10.9% of the workers. The estimated frequency of irritant contact dermatitis caused by work was 6.1%. Dermatitis on the hands was associated with contact allergy to epoxy resin (P = 0.017). The number of days on leave before the clinical examination was negatively associated with the presence of dermatitis (P = 0.001). Among workers employed 7–12 months, the frequency of occupational contact allergy was higher than that among workers employed for ≤6 months (P = 0.004). Females both washed their hands more often (P < 0.001) and used more moisturizers/protection creams at work (P < 0.001) than males. No sex differences were found concerning dermatitis on the hands.
Allergenicity evaluation of Bioban CS‐1135 in experimental animals
Authors: Yamano Tetsuo , Shimizu Mitsuru , Noda Tsutomu
Published: July 2004

An industrial preservative, Bioban CS‐1135, was evaluated for its contact allergenicity by means of multiple‐dose guinea‐pig maximization test and non‐radioactive murine local lymph node assay. In the guinea‐pig test, an induction dose of 0.5% Bioban CS‐1135 sensitized all animals of the group. The dose–response study of the elicitation phase determined a minimum elicitation dose of 5% for positive skin reactions. In the murine assay, Bioban CS‐1135 at doses of 10% and more exerted significant effects on lymphoid cell proliferation. Although the data clearly designated Bioban CS‐1135 as a skin sensitizer, its relative potency was ranked lowest among skin‐sensitizing biocides previously evaluated in this laboratory.
Hair dye contact allergy: quantitative exposure assessment of selected products and clinical cases
Authors: SØsted Heidi , Rastogi Suresh Chandra , Andersen Klaus Ejner , Johansen Jeanne Duus , Menné Torkil
Published: July 2004

Colouring of hair can cause severe allergic contact dermatitis. The most frequently reported hair dye allergens are p‐phenylenediamine (PPD) and toluene‐2,5‐diamine, which are included in, respectively, the patch test standard series and the hairdressers series. The aim of the present study was to identify dye precursors and couplers in hair dyeing products causing clinical hair dye dermatitis and to compare the data with the contents of these compounds in a randomly selected set of similar products. The patient material comprised 9 cases of characteristic clinical allergic hair dye reaction, where exposure history and patch testing had identified a specific hair dye product as the cause of the reaction. The 9 products used by the patients were subjected to chemical analysis. 8 hair dye products contained toluene‐2,5‐diamine (0.18 to 0.98%). PPD (0.27%) was found in 1 product, and m‐aminophenol (0.015 to 0.38%) and p‐aminophenol (0.16 to 2.1%) were found in 3 products. The concentration levels were similar in the patient's products compared to a random sample of 16 hair dye products. The concentration present of toluene‐2,5‐diamine elicited allergic reactions in concentrations that were 10‐fold lower than the legal EU limit of 10%. Hair dye allergy may cause severe clinical reactions, and the current regulation is insufficient in protection of the users. A preventive strategy is needed.
Systemically induced allergic exanthem from mercury
Authors: Lerch Marianne , Bircher Andreas J.
Published: July 2004

Cutaneous reactions to mercury can manifest themselves in different forms. Apart from contact dermatitis, flare‐up reactions, disseminated exanthem as well as skin symptoms in previously unaffected skin are known. Regarding systemic allergen application, 2 separate clinical patterns, namely acute generalized exanthematous pustulosis (AGEP) and symmetric flexural exanthem ‘baboon syndrome’ have been described. Systemic allergic reactions to mercury are most commonly provoked by the inhalation of metallic mercury vapours from a broken thermometer, often after previous sensitization to mercury compounds, e.g. Mercurochrome. Patch testing with mercurials yields positive reactions in approximately 80% of patients. We report 3 patients, 2 with flexural exanthem, and 1 presenting with AGEP, respectively. Positive patch tests to mercury derivatives could be demonstrated in all of them. Furthermore, non‐toxic serum mercury levels were detected in 2 of the patients. The present review provides a survey of the literature on systemic allergic exanthem to mercury. However, plausible explanations for the distribution pattern of the skin manifestations in AGEP and flexural exanthem are still lacking.
Low negative predictive value of skin tests in investigating delayed reactions to radio‐contrast media
Authors: Vernassiere C. , Trechot P. , Commun N. , Schmutz J.‐L. , Barbaud A.
Published: July 2004

Delayed reactions to radio‐contrast media (RCM) with positive skin tests are rare. We report the study of a series of 15 patients who presented delayed reactions to RCM, with an analysis of the clinical features and the results of standardized drug skin tests. Patch tests were performed with RCM and iodized antiseptics (IAs). If negative, prick tests were performed, followed by intradermal tests (IDTs), then intravenous administration under hospital surveillance. The main clinical features were maculopapular rashes or a macular rubella‐like rashes. Patch tests were positive with RCM in 2 of 15 cases and with IAs in 4 of 15 cases. All the prick tests were negative. IDTs were positive at 24 h in 8 of 15 cases. 5 of 12 patients had a non‐severe relapse of the rash upon receiving an RCM despite clearly negative skin tests with the readministered RCM. Visipaque® cross‐reacted with Iopamiron®, Iomeron®, Telebrix®, Omnipaque®, Xenetix® and Hexabrix®. Omnipaque® cross‐reacted with Hexabrix® and Iopamiron®. IDTs with delayed readings are of better value than patch tests in such patients. The readministration of RCM with negative IDTs must be performed with progressive amounts under hospital surveillance. Cross‐reactions between various classes of RCM are frequent. The responsible epitopes are unknown. Iodine itself could be involved.