bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal Cord Ependymoma: Radical Surgical Resection and Outcome
Authors: Hanbali Fadi , Fourney Daryl R. , Marmor Eric , Suki Dima , Rhines Laurence D. , Weinberg Jeffrey S. , McCutcheon Ian E. , Suk Ian , Gokaslan Ziya L.
Published: July 2004

OBJECTIVE

Several authors have noted increased neurological deficits and worsening dysesthesia in the postoperative period in patients with spinal cord ependymoma. We describe the neurological progression and pain evolution of these patients over the 1-year period after surgery. In addition, our favored method of en bloc tumor resection is illustrated, and the rate of complications, recurrence, and survival in this group of patients is addressed.

METHODS

We operated on 26 patients (12 male and 14 female) with low-grade spinal cord ependymomas between 1975 and 2001. The median age at diagnosis was 42 years. Tumors extended into the cervical cord in 13 patients, the thoracic cord in 7 patients, and the conus medullaris in 6 patients. Eleven patients had previous surgery and/or radiation therapy.

RESULTS

We achieved a gross total resection in 88% of patients, whereas 8% had a subtotal resection and 4% had a biopsy. Only 1 patient developed a recurrence over a mean follow-up period of 31 months.

CONCLUSION

We conclude that radical surgical resection of spinal cord ependymomas can be safely achieved in the majority of patients. A trend toward neurological improvement from a postoperative deficit can be expected between 1 and 3 months after surgery and continues up to 1 year. Postoperative dysesthesias begin to improve within 1 month of surgery and are significantly better by 1 year after surgery. The best predictor of outcome is the preoperative neurological status.
Allograft Implants for Posterior Lumbar Interbody Fusion: Results Comparing Cylindrical Dowels and Impacted Wedges
Authors: Barnes Bryan , Rodts Gerald E. , Haid Regis W. , Subach Brian R. , McLaughlin Mark R.
Published: July 2004

OBJECTIVE

With the proliferation of implant types available for use in posterior lumbar interbody fusion (PLIF) procedures, the choices for surgeons have become increasingly complex. The goal of this study was to retrospectively review a series of 49 patients who underwent PLIF with the use of allograft cylindrical threaded cortical bone dowels (TCBDs) and allograft impacted wedges. Nerve root injury rates, fusion rates, and clinical outcomes of the allograft impacted wedge group are compared with those in the allograft cylindrical TCBD group.

METHODS

We performed a retrospective chart and radiographic review of 49 patients. Twenty-seven patients underwent PLIF with impacted allograft wedges, and 22 patients underwent PLIF with allograft cylindrical TCBD. Permanent nerve root injury rates, fusion rates, and clinical outcomes were assessed on the basis of a minimum of 1 year of follow-up data in this nonconsecutive series.

RESULTS

Permanent nerve root injuries in the impacted wedge and TCBD groups were documented with physical examinations conducted pre- and postoperatively. The cylindrical TCBD group showed a 13.6% rate of permanent nerve root injury, and the impacted wedge group demonstrated a 0% rate, and these rates were statistically significant (analysis of variance, P = 0.049). The fusion rate at a mean of 13.9 months of follow-up was 95.4% in patients in whom the cylindrical TCBD was implanted and 88.9% after a mean of 17.4 months of follow-up in patients in whom impacted wedges were used. The fusion rate difference between the TCBD and impacted wedge groups was not significant. The satisfactory outcome rate was 72.7% for the TCBD group and 85.1% for the impacted wedge group, and the impacted wedge group was found to have a significantly higher rate of satisfactory outcomes (P = 0.016, analysis of variance). Analysis of the patient outcomes in the TCBD and impacted wedge groups according to sex, mean length of follow-up, workman's compensation claim rate, and smoking habit yielded no significant difference.

CONCLUSION

With a minimum of 1 year of follow-up in this nonconsecutive series of 49 patients, a comparison of the use of allograft TCBD versus allograft impacted wedges in PLIF procedures reveals a statistically significant increase in permanent nerve root injury rates with the use of cylindrical TCBD implants as compared with impacted allograft wedges. There is no difference between the two groups in terms of fusion rates, and clinical outcomes with the use of impacted wedges were significantly better.
Comparison of Posterior Approaches to the Posterior Incisural Space: Microsurgical Anatomy and Proposal of a New Method, the Occipital Bi-transtentorial/Falcine Approach
Authors: Kawashima Masatou , Rhoton Albert L. , Matsushima Toshio
Published: July 2004

OBJECTIVE

Direct surgical approaches to the posterior incisural space, including the pineal region, remain as challenges for neurosurgeons. The purposes of this study were 1) to compare the surgical views in the various posterior approaches to the posterior incisural space and 2) to propose a new approach, which is a modification of the occipital transtentorial approach.

METHODS

Ten adult cadaveric specimens (20 sides) were studied, using ×3 to ×40 magnification, after perfusion of the arteries and veins with colored silicone. Intraoperative views in the posterior approaches to lesions were examined in stepwise dissections. In addition, the efficacy of the occipital bi-transtentorial/falcine approach was studied.

RESULTS

The posterior incisural space has a roof, a floor, and anterior and lateral walls and extends backward to the level of the tentorial apex. The operative views defined by each approach differ in the extent to which they allow observation of the anatomic structures in the posterior incisural space. The occipital bi-transtentorial/falcine approach permits better observation of the contralateral half of the quadrigeminal cistern.

CONCLUSION

Precise surgical anatomic knowledge of each approach is required for the treatment of lesions in the posterior incisural space, because the operative fields obtained with different approaches differ significantly. The occipital bi-transtentorial/falcine approach provides greater contralateral exposure of the posterior incisural space than does the occipital transtentorial approach.
Imaging the Cerebrovascular Tree in the Cadaveric Head for Planning Surgical Strategy
Authors: Zhao Jin-Cheng , Chen Chi , Rosenblatt Sami S. , Meyer Joel R. , Edelman Robert R. , Batjer H. Hunt , Ciric Ivan S.
Published: July 2004

OBJECTIVE

The objective of the study was to identify whether an integration of cadaveric dissections with preoperative imaging information may enable a better understanding of pathological anatomy, especially vascular lesions, and thus allow for greater precision in surgical planning.

METHODS

We selected a computed tomographic contrast agent and experimentally determined the proportion of it that could mix compatibly with the silicone compound. The resultant mixture was injected into the cerebrovascular systems of six fresh human cadaveric heads. The specimens underwent computed tomography for the purpose of digital virtual exposures in parallel with laboratory dissections performed on these specimens.

RESULTS

The 1:8 ratio of contrast agent to silicone rubber was determined to be appropriate for both computed tomography and subsequent laboratory dissection of the specimens. The blood vessels in computed tomographic scans demonstrated a higher attenuation than surrounding soft tissues. The opacity consistency of the injected vessels was a critical parameter for a clear three-dimensional rendering of the vascular structures in the natural surroundings of the skull base. Static and dynamic three-dimensional images of the cadaveric vascular tree were obtained as viewed through surgical corridors of various skull base approaches.

CONCLUSION

We demonstrated a new cadaveric preparation model for imaging and dissection. This model allows for static and dynamic three-dimensional examination of the surgical anatomy from a neurosurgeon's perspective. It may facilitate the study of cerebrovascular system morphology/pathology in relation to the skull base as a tool for surgical planning.
Peripheral Primitive Neuroectodermal Tumor of the Jugular Foramen: Case Report
Authors: Yamazaki Takamasa , Kuroki Takao , Katsume Mikiro , Kameda Noriaki
Published: July 2004

OBJECTIVE AND IMPORTANCE

Peripheral primitive neuroectodermal tumor (pPNET) is a rare type of tumor, most commonly found in the limbs of children and young adults. The authors report an extremely rare case of pPNET located at the jugular foramen whose clinical course demonstrated rapid progression.

CLINICAL PRESENTATION

A 23-year-old man presented with a 2-month history of progressive hoarseness and dysphagia. The neuroradiological appearance of the lesion was a jugular foramen tumor.

INTERVENTION

The patient underwent a partial resection of the tumor through a far lateral suboccipital craniotomy. After surgery, the patient experienced an unexpected deterioration in consciousness. Magnetic resonance images on postoperative Day 18 revealed rapid and large expansion of the residual tumor into the posterior fossa. No adjuvant therapy was administered, and the patient died 6 weeks after diagnosis.

CONCLUSION

The pathological diagnosis of the surgical specimen was pPNET, according to the findings of hematoxylin and eosin and immunohistochemical stainings. To the best of our knowledge, this is the first reported case of pPNET at the jugular foramen.
Supratentorial Convexity Leptomeningeal Schwannoma: Case Report
Authors: Nakayama Keiko , Nakayama Tetsuo , Matsuoka Yoshimi , Kono Kinuko
Published: July 2004

OBJECTIVE AND IMPORTANCE

Leptomeningeal schwannomas are very rare; to our knowledge, only one case has been previously reported. The possible histogenesis and differential diagnosis of intracranial schwannomas not related to cranial nerves are discussed.

CLINICAL PRESENTATION

A 53-year-old man presented with a sudden onset of seizures. Computed tomographic scans revealed a small hypodense mass in the peripheral aspect of the left frontal lobe. The mass was hypointense on T1-weighted and hyperintense on T2-weighted magnetic resonance imaging scans, with ring enhancement after contrast medium administration.

INTERVENTION

A craniotomy was performed for total removal of the tumor, revealing a well-demarcated, firm, spherical tumor beneath the dura. The tumor was easily separated from the brain. Histologically, the tumor was observed to be within the subarachnoid space, intimately attached to the pia mater. The adjacent brain tissue and dura mater were free of tumor cells. The histological diagnosis was schwannoma.

CONCLUSION

Computed tomographic and magnetic resonance imaging findings in our case were consistent with those for a schwannoma, although the subarachnoid space is an extremely rare location for schwannomas. We emphasize that schwannomas may arise in the subarachnoid space.
Thoracoscopic Approaches to the Thoracic Spine: Experience with 241 Surgical Procedures
Authors: Han Patrick P. , Kenny Kathy , Dickman Curtis A.
Published: July 2004

INTRODUCTION

Microsurgical thoracoscopic approaches to the thoracic spine allow access to the spinal cord, spinal nerves, disc spaces, vertebral bodies, paravertebral soft tissues, and sympathetic chain with minimal invasiveness.

METHODS

Between January 1994 and January 2000, 241 thoracoscopic procedures were performed: 164 thoracic sympathectomies, 60 discectomies, 5 neurogenic tumor resections, 8 corpectomies and spinal reconstructions, 2 anterior releases, and 2 biopsies. Cases were reviewed to evaluate the efficacy, surgical results, and complications of the thoracoscopic procedures.

RESULTS

An adequate sympathectomy was achieved in all 164 sympathectomies. There was 100% relief of palmar and 95% relief of axillary hyperhidrosis. Reflex sympathetic dystrophy responded poorly to sympathectomy with recurrent pain. Thoracoscopic discectomy achieved complete decompression in 98% of patients. Gross total tumor resection was achieved in all five paraspinal neurogenic tumors. There was no operative mortality. Morbidity compared favorably with open surgical approaches to the thoracic spine.

CONCLUSION

Thoracoscopic spinal surgery is an effective technique that provides full, direct access to the ventral thoracic spine. Its morbidity rate appears to be lower than that associated with open thoracotomy. It improves patient comfort and cosmetic results and shortens recovery. This technique has become the authors' surgical approach of choice for removing benign intrathoracic paraspinal neurogenic tumors and central herniated thoracic discs and for performing biopsies and thoracic sympathectomies. The senior author still prefers open surgical approaches for most thoracic corpectomies and spinal reconstruction procedures.
Thoracoscopic-assisted Treatment of Thoracic and Lumbar Fractures: A Series of 371 Consecutive Cases
Authors: Khoo Larry T. , Beisse Rudolf , Potulski Michael
Published: July 2004

OBJECTIVE

Conventional approaches for the treatment of thoracic and thoracolumbar fractures require extensive surgical exposure, often leading to significant postoperative pain and morbidity. Thoracoscopic spinal surgery was performed to reduce the morbidity of these approaches while still achieving the primary goals of spinal decompression, reconstruction, and stabilization.

METHODS

Between May 1996 and May 2001, 371 patients with fractures of the thoracic and thoracolumbar spine (T3–L3) were treated with a thoracoscopically assisted procedure. In the first 197 patients, a conventional open anterior plating system was used. The last 174 patients were treated with the MACS-TL system (Aesculap, Tuttlingen, Germany), which was designed specifically for endoscopic placement, thereby significantly reducing operative times.

RESULTS

Seventy-three percent of the fractures were located at the thoracolumbar junction. In 49% of patients, mobilization of the diaphragm was performed to expose the fracture, with later repair. Both x-ray canal compromise and neural deficit were present in 15% of patients. In 35% of patients, a stand-alone anterior thoracoscopic reconstruction was performed. In 65% of patients, a supplemental posterior pedicle-screw construct was also placed either before or after the anterior construct. A steep learning curve was present, with an average operating time of 300 minutes in the first 50% of cases and an average of 180 minutes with the MACS-TL system. The severe complication rate was low (1.3%), with one case each of aortic injury, splenic contusion, neurological deterioration, cerebrospinal fluid leak, and severe wound infection. Compared with a group of 30 patients treated with open thoracotomy, thoracoscopically treated patients required 42% less narcotics for pain treatment after the operation.

CONCLUSION

A complete anterior thoracoscopically assisted reconstruction of thoracic and thoracolumbar fractures can be safely and effectively accomplished, thereby reducing the pain and morbidity associated with conventional thoracotomy and thoracolumbar approaches. Although the learning curve is steep, the functional and cosmetic benefits to the patient warrant the difficult training process.
Microendoscopic Decompressive Laminotomy for the Treatment of Lumbar Stenosis
Authors: Khoo Larry T. , Fessler Richard G.
Published: July 2004

OBJECTIVE

By modifying existing microendoscopic discectomy techniques, we previously developed a novel surgical treatment of lumbar stenosis and validated its ability to achieve a thorough decompression in a cadaveric study. We now describe our clinical experience with this new, minimally invasive microendoscopic decompressive laminotomy (MEDL) technique.

METHODS

A MEDL was performed in 25 patients with classic features of lumbar stenosis. By use of a fluoroscopically guided percutaneous technique, the working portal was docked on the lamina with minimal soft-tissue injury. With the angle of the endoscope combined with an oblique entry, a bilateral bony and ligamentous decompression was achieved under the midline, thereby preserving the supraspinous–interspinous ligaments and contralateral musculature. A second group of 25 patients treated with open decompression was used for comparison.

RESULTS

Effective circumferential decompression was achieved in the majority of patients. The results for the MEDL group were as follows: operative time, 109 minutes per single level; blood loss, 68 ml; and postoperative stay, 42 hours. The results for the open-surgery group were as follows: operative time, 88 minutes; blood loss, 193 ml; and postoperative stay, 94 hours. The MEDL group needed significantly less narcotic medication after surgery. Overall, 16% of the MEDL patients reported resolution of their back pain, 68% improved symptomatically, and 16% remained unchanged. The outcome of the open group was very similar.

CONCLUSION

Compared with an equivalent open technique, MEDL appears to offer a similar short-term clinical outcome with a significant reduction in operative blood loss, postoperative stay, and use of narcotics. This lower surgical stress, decreased tissue trauma, and quicker recovery are particularly important in this elderly population of patients.
Is Laparoscopic Anterior Lumbar Interbody Fusion a Useful Minimally Invasive Procedure?
Authors: Liu John C. , Ondra Stephen L. , Angelos Peter , Ganju Aruna , Landers Misty L.
Published: July 2004

OBJECTIVE

Laparoscopic anterior lumbar interbody fusion (LALIF) has been demonstrated to be safe and effective. Its use as a standard surgical technique has been recommended for arthrodesis in the lumbosacral region. We reviewed our experience with LALIF for safety, effectiveness, and usefulness.

METHODS

Retrospective review of 14 patients who underwent LALIF was performed. All patients had a diagnosis of degenerative disc disease with medically retractable mechanical back pain.

RESULTS

No intraoperative vascular or neurological injury was encountered. An average operating time of 300 minutes with blood loss of 60 ml was found. The average hospital stay was 3.4 days. At 3 to 6 months after surgery, 80% fusion rates were achieved.

CONCLUSION

Although LALIF is a safe and effective procedure, it has many disadvantages, which make it a less than optimal procedure for routine use. Other minimally invasive approaches to the anterior lumbar spine result in similar beneficial results without the drawbacks associated with LALIF.
Minimally Invasive Percutaneous Posterior Lumbar Interbody Fusion
Authors: Khoo Larry T. , Palmer Sylvain , Laich Daniel T. , Fessler Richard G.
Published: July 2004

OBJECTIVE

The wide exposure required for a standard posterior lumbar interbody fusion (PLIF) can cause unnecessary trauma to the lumbar musculoligamentous complex. By combining existing microendoscopic, percutaneous instrumentation and interbody technologies, a novel, minimally invasive, percutaneous PLIF technique was developed to minimize such iatrogenic tissue injury (MIP-PLIF).

METHODS

The MIP-PLIF technique was validated in three cadaveric torsos with six motion segments decompressed and fused. Preoperative variables measured from imaging included interpedicular distance, pedicular height and width, interspinous distance, lordosis, intervertebral height, Cobb angle, and foraminal height and volume. Using the METRx and MD spinal access systems (Medtronic Sofamor Danek, Memphis, TN), bilateral laminotomies were performed using a hybrid of microsurgical and microendoscopic techniques. The intervertebral disc spaces were then distracted and prepared with the Tangent (Medtronic Sofamor Danek) interbody instruments. Either a 10 or 12 by 22 mm interbody graft was then placed. Using the Sextant (Medtronic Sofamor Danek) system, percutaneous pedicle screw-rod fixation of the motion segment was completed. We then applied MIP-PLIF in three patients.

RESULTS

For segments with preoperative intervertebral/foraminal height loss, MIP-PLIF was effective in restoring both heights in all cases. The amount of improvement (9.7 to 38% disc height increase; 7.7 to 29.9% foraminal height increase) varied directly with the size of the graft used and the original degree of disc and foraminal height loss. Segmental lordosis improved by 29% on average. Graft and screw placement was accurate in the cadavers, except for a single Grade 1 screw violation of one pedicle. The average operative time was 3.5 hours per level. In our three clinical cases, the MIP-PLIF procedure required a mean of 5.4 hours, estimated blood loss was 185 ml, and inpatient stay was 2.8 days, with no intravenous narcotic use after 2 days in any of the patients. All screw and graft placements were confirmed.

CONCLUSION

A complete PLIF procedure can be safely and effectively performed using minimally invasive techniques, thereby potentially reducing the pain and morbidity associated with standard open surgery. Prospective, randomized outcome studies will be required to validate the efficacy of this exciting new surgical technique.
Contributions of Striatal Subregions to Place and Response Learning
Authors: Yin Henry H. , Knowlton Barbara J.
Published: July 2004

The involvement of different subregions of the striatum in place and
response learning was examined using a T-maze. Rats were given NMDA lesions of
the dorsolateral striatum (DLS), anterior dorsomedial striatum (ADMS),
posterior dorsomedial striatum (PDMS), or sham surgery. They were then trained
to retrieve food from the west arm of the maze, starting from the south arm,
by turning left at the choice point. After 7 d of training, with four trials a
day, a probe test was given in which the starting arm is inserted as the north
arm, at the opposite side of the maze. A left turn would indicate a
“response” strategy; a right turn, a “place” strategy.
The rats were then trained for 7 more days, followed by a second probe test.
Unlike rats in the other groups, most of the rats in the PDMS group turned
left, using the response strategy on both probe tests. These results suggest
that the PDMS plays a role in spatially guided behavior.
The Roles of MAPK Cascades in Synaptic Plasticity and Memory in
Aplysia: Facilitatory Effects and Inhibitory Constraints: Figure 1
Authors: Sharma Shiv K. , Carew Thomas J.
Published: July 2004

Synaptic plasticity is thought to contribute to memory formation.
Serotonin-induced facilitation of sensory-motor (SN-MN) synapses in
Aplysia is an extensively studied cellular analog of memory for
sensitization. Serotonin, a modulatory neurotransmitter, is released in the
CNS during sensitization training, and induces three temporally and
mechanistically distinct phases of SN-MN synaptic facilitation. The role of
protein kinase A and protein kinase C in SN-MN synaptic facilitation is well
documented. Recently, it has become clear that mitogen-activated protein
kinase (MAPK) cascades also play a critical role in SN-MN plasticity. Here, we
summarize the roles of MAPK cascades in synaptic plasticity and memory for
sensitization in Aplysia.
Lichen Striatus: Description of 89 Cases in Children
Authors: Taniguchi Abagge Kerstin , Parolin Marinoni Leide , Giraldi Susana , Carvalho Vânia O. , De Oliveira Santini Cíntia , Favre Henrique
Published: July 2004

Abstract:  Lichen striatus (LS) is a benign, self‐limited, linear, inflammatory dermatosis of unknown etiology that usually affects children. We analyzed 89 cases in regard to age of appearance, sex, race, symptoms, seasonal incidence, localization of lesions and affected side of the body, and presence of atopy. Lesions predominated on the inferior limbs, with no preponderance of any age, and were asymptomatic in the majority of the instances. There was no difference in the incidence of LS in regard to the season of the year. A possible association of lichen sclerosus with atopy and pruritus was observed.
Unilateral Aplasia Cutis Congenita on the Leg
Authors: Bigliardi Paul Lorenzo , Braschler Claudia , Kuhn Peter , Sigrist Johannes , Buechner Stanislaw , Rufli Theo
Published: July 2004

Abstract:  We present the case of a newborn male with aplasia cutis congenita on the extensor side of the right leg, with unilateral absence of skin on the lower limb. There was no abnormality in pregnancy or birth and there was no associated malformation or skin disease such as blistering or nail pathology. The management of this large ulcer was conservative, using silver sulfadiazine ointment, and healing occurred within 3 months. The follow‐up after 21 months showed little scar formation and no handicap regarding function and appearance. The psychomotor development was normal. According to the classification outlined by Frieden, we classified this condition as type VII aplasia cutis congenita.
Palmoplantar Eccrine Hidradenitis: Seven New Cases
Authors: Rubinson Rebeca , Larralde Margarita , Santos‐Muñoz Andrea , Parra Viviana , De Parra Nelida Pizzi
Published: July 2004

Abstract:  Palmoplantar eccrine hidradenitis is a self‐limited disease characterized by painful erythematous papules and nodules of abrupt onset on the soles, and less frequently on the palms, of young individuals in good health. We describe seven children, four girls and three boys, between 4 and 12 years of age, with characteristic cutaneous and histopathologic findings of palmoplantar eccrine hidradenitis. All patients had complete resolution of their lesions within 2–4 weeks without treatment, however, one child experienced recurrences. All skin biopsy specimens showed a deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands, the histologic hallmark of the disease. Palmoplantar eccrine hidradenitis is a distinct clinical entity in which physical activity, excessive sweating, and prolonged wetness are possible triggering factors. The regression of the lesions is usually rapid, with complete clearance after 1 month, although there may be recurrent episodes.
Germline transcription of multiple TCR‐Vβ genes in cloned T‐cell lines
Authors: Abbey Janice L , O'Neill Helen C
Published: July 2004

The functional significance of germline transcription of T cell receptor (TCR) beta chain variable (V) region genes is under investigation. The accepted model is that transcriptional activation of germline TCR genes is associated with the rearrangement process during T‐cell development. By this model, germline expression of a subset of TCR‐Vβ genes might be expected in early T cells which have not yet undergone rearrangement. Germline transcription of TCR‐Vβ genes was analysed using the reverse transcriptase (RT)‐PCR in a clonal T‐cell precursor line C1‐V13D, a clonal pre‐B cell line RAW112 and a mature T helper cell line D10.G4.1. Evidence is presented for germline transcription of TCR‐Vβ8.2 and TCR‐Vβ2.1 genes in all three cell lines, although expression in RAW112 was very weak. C1‐V13D cells expressed very high levels of the whole range of transcripts including Vβ2.1, Vβ5.1, Vβ5.2, Vβ6.1, Vβ7.1, Vβ8.1, Vβ8.2, Vβ8.3 and Vβ13.1. However, D10.G4.1 cells expressed a subset of transcripts with apparently lower levels of expression, including Vβ2.1, Vβ5.1, Vβ5.2, Vβ6.1, Vβ8.2 and Vβ8.3. These results raise questions about the significance and possible function of germline transcripts and/or their encoded products in early lymphoid cells and in T cells at different stages of development.
Double‐stranded RNA enhances the expression of galectin‐9 in vascular endothelial cells
Authors: Ishikawa Akira , Imaizumi Tadaatsu , Yoshida Hidemi , Nishi Nozomu , Nakamura Takanori , Hirashima Mitsuomi , Satoh Kei
Published: July 2004

Treatment of cells with double‐stranded RNA (dsRNA) in vitro mimics viral infection and regulates expression of various genes. We addressed the mechanisms of leucocyte traffic across the vascular endothelium induced by dsRNA. The present study focused on the expression of galectin‐9, which is one of key molecules in the regulation of the interaction between vascular wall and white blood cells. Human umbilical vein endothelial cells (HUVEC) in culture were treated with polyinosinic‐polycytidylic acid (poly IC), and expression of mRNA and protein of galectin‐9 was analysed by reverse transcription polymerase‐chain reaction (RT‐PCR) and Western blotting. Poly IC enhanced the expression of galectin‐9 mRNA and protein in concentration‐ and time‐dependent manners. This effect of poly IC was almost completely suppressed by the pretreatment with 2‐aminopurine, an inhibitor of dsRNA‐dependent kinase. Poly IC treatment of HUVEC also enhanced the adherence of EoL‐1 cells to the cells, which was inhibited by co‐treatment with lactose. We conclude that poly IC upregulates galectin‐9 expression in the vascular endothelium and this may explain part of the mechanism for leucocyte traffic through the vascular wall.
On ‘reactivity’ versus ‘tolerance’
Authors: Zinkernagel Rolf M
Published: July 2004

In Burnet's review on ‘The impact of ideas on immunology’ he considers himself an observer of nature using biochemical and molecular analysis for more detailed understanding, a description that applies also to me. I use three examples − repertoire selection of T cells, rules of immune reactivity versus non‐reactivity and immunological memory − to illustrate the difficulties we all have in probing nature's immunological secrets and in critically testing immunologists’ ideas. At one end of the spectrum of biological research one may argue everything is possible and therefore all results are correct, if correctly measured. But perhaps it is more important to always ask again and again what is frequent and enhances survival versus what is rare and an exception. At the same time one must keep in mind that special situations and special tricks may well be applied for medical benefits, although they may have little impact on physiology and species survival. I will attempt to use disease in virus‐infected mice to obtain some answers to what I consider to be important immunological questions with the hope of improving the ratio of answers that are right for the right experimental reasons versus those that are right for the wrong reasons. Some of these experiments falsify hypotheses, previous experiments and interpretations and therefore are particularly important in correcting misleading concepts. They should help to find out which half of immunological ideas and truths in immunological text books written today are likely to be wrong. Ideas are important in immunology, but are often rather demagogically handled and therefore may cost us very dearly indeed. Evaluating immunity to infections and tumours in vivo should help prevent us from getting lost in immunology.
cAMP controls human renin mRNA stability via specific RNA‐binding proteins
Authors: Morris B. J. , Adams D. J. , Beveridge D. J. , van der Weyden L. , Mangs H. , Leedman P. J.
Published: July 2004

It is now recognized that post‐transcriptional mechanisms are pivotal to renin production. These involve factors that modulate renin mRNA stability. In 2003 new data has emerged from work in Australia and Germany that has identified several of the, as many as, 20 or so proteins involved. These include CP1 (hnRNP E1), HuR, HADHB, dynamin, nucleolin, YP‐1, hnRNP K and MINT‐homologous protein. Cyclic AMP (cAMP) is a crucial regulator of renin secretion as well as transcriptional and post‐transcriptional control of expression. Many of the RNA‐binding proteins that were identified responded to forskolin, increasing in amount by two to 10‐fold. The cAMP mechanisms that regulate renin mRNA target, at least in large part, other genes that presumably encode some of these proteins. The increase in the expression of these then facilitates, sequentially, renin mRNA stabilization and destabilization. Our data, using a battery of different techniques, confirm that CP1 and HuR stabilize renin mRNA, whereas HADHB causes destabilization. These proteins target cis‐acting C‐rich sequences (in the case of CP1) and AU‐rich sequences (HuR) in the distal region of the 3′‐untranslated region of renin mRNA. We found HADHB was enriched in juxtaglomerular cells and that that within Calu‐6 cells HADHB, HuR and CP1 all localized in nuclear subregions, as well as cytoplasm (HADHB and CP1) and mitochondria (HADHB) commensurate with the role each plays in control of renin mRNA stability. The specific proteins that bind to human renin mRNA have begun to be revealed. Cyclic AMP upregulates the binding of several of these proteins, which in turn affect renin mRNA stability and thus overall expression of renin.
Rapid non‐genomic effects of aldosterone on rodent vascular function
Authors: Uhrenholt T. R. , Schjerning J. , Rasmussen L. E. , Hansen P. B. , Nørregaard R. , Jensen B. L. , Skøtt O.
Published: July 2004

The main role of aldosterone is to maintain body sodium homeostasis by promoting salt reabsorption in the collecting ducts of the kidney. In the cardiovascular system, aldosterone may be harmful in a number of disease states by inducing fibrosis and vascular dysfunction. The present review describes novel results from several laboratories, which show that aldosterone also has beneficial effects in the cardiovascular system by stimulating the production of nitric oxide (NO) from the endothelium. The effect of aldosterone is seen within minutes, and is not inhibited by blockers of gene transcription, thus pointing to a non‐genomic mechanism. Furthermore, this potentially beneficial effect is observed at low physiological concentrations of aldosterone (0.1–10 pm). The effect is mediated by the classical mineralocorticoid receptor, and it involves heat shock protein 90, phosphatidylinositol (PI)‐3 kinase, protein kinase B, endothelial nitric oxide synthase, and liberation of NO. It is proposed that in healthy individuals with a functioning NO system, the detrimental effects of aldosterone on cardiovascular function are balanced by activation of the potentially beneficial effect of NO. However, in situations with endothelial dysfunction, such as congestive heart failure and hypertension, the negative effects of aldosterone are unopposed and inhibition of aldosterone is warranted.
Calcium handling in afferent arterioles
Authors: Salomonsson M. , Sorensen C. M. , Arendshorst W. J. , Steendahl J. , Holstein‐Rathlou N.‐H.
Published: July 2004

The cytosolic intracellular calcium concentration ([Ca2+]i) is a major determining factor in the vascular smooth muscle tone. In the afferent arteriole it has been shown that agonists utilizing G‐protein coupled receptors recruit Ca2+ via release from intracellular stores and entry via pathways in the plasma membrane. The relative importances of entry vs. mobilization seem to differ between different agonists, species and preparations. The entry pathway might include different types of voltage sensitive Ca2+ channels located in the plasmalemma such as dihydropyridine sensitive L‐type channels, T‐type channels and P/Q channels. A role for non‐voltage sensitive entry pathways has also been suggested. The importance of voltage sensitive Ca2+ channels in the control of the tone of the afferent arteriole (and thus in the control of renal function and whole body control of extracellular fluid volume and blood pressure) sheds light on the control of the membrane potential of afferent arteriolar smooth muscle cells. Thus, K+ and Cl− channels are of importance in their role as major determinants of membrane potential. Some studies suggest a role for calcium‐activated chloride (ClCa) channels in the renal vasoconstriction elicited by agonists. Other investigators have found evidence for several types of K+ channels in the regulation of the afferent arteriolar tone. The available literature in this field regarding afferent arterioles is, however, relatively sparse and not conclusive. This review is an attempt to summarize the results obtained by others and ourselves in the field of agonist induced afferent arteriolar Ca2+ recruitment, with special emphasis on the control of voltage sensitive Ca2+ entry. Outline of the Manuscript: This manuscript is structured as follows: it begins with an introduction where the general role for [Ca2+]i as a key factor in the regulation of the tone of vascular smooth muscles (VSMC) is detailed. In this section there is an emphasis is on observations that could be attributed to afferent arteriolar function. We then investigate the literature and describe our results regarding the relative roles for Ca2+ entry and intracellular release in afferent arterioles in response to vasoactive agents, with the focus on noradrenalin (NA) and angiotensin II (Ang II). Finally, we examine the role of ion channels (i.e. K+ and Cl− channels) for the membrane potential, and thus activation of voltage sensitive Ca2+ channels.
Compensation of proximal tubule malabsorption in AQP1‐deficient mice without TGF‐mediated reduction of GFR
Authors: Hashimoto S. , Huang Y. , Mizel D. , Briggs J. , Schnermann J.
Published: July 2004

Aim:  By crossing aquaporin 1 (AQP1)−/− and adenosine 1 receptor (A1AR)−/− mice, we generated an animal model that combines a proximal tubular absorption defect with absence of tubuloglomerular feedback (TGF) regulation of glomerular filtration rate (GFR). The aim of studies in these animals was to determine whether a TGF‐induced reduction of GFR is a prerequisite for preventing potentially fatal fluid losses.

Methods and Results:  In contrast to AQP1 deficient mice, AQP1/A1AR−/− mice were found to have a normal GFR. TGF responses were abolished in these animals, in contrast to AQP1−/− mice in which TGF responses of single nephron glomerular filtration rate (SNGFR) were left‐shifted. Proximal tubule fluid absorption in AQP1/A1AR−/− mice was reduced to levels previously reported for AQP1−/− mice. However, SNGFR was significantly higher in AQP1/A1AR−/− than AQP1−/− mice (10.6 ± 0.8 nL min−1 vs. 5.9 ± 0.7 nL min−1). As a consequence of the normal GFR and the reduced proximal reabsorption distal fluid delivery was markedly higher in the double knockout compared with normal or AQP1−/− mice (5.5 ± 0.5 nL min−1 vs. 2.35 ± 0.3 nL min−1 in AQP1−/−). Despite the approximate doubling of distal fluid and Cl delivery, AQP1/A1AR−/− mice have a normal salt excretion, normal arterial blood pressure, and only a small increase in plasma renin concentration.

Conclusion:  The ability to compensate for proximal tubule malabsorption without a TGF‐induced reduction of GFR attests to a remarkable adaptability of distal tubule transport mechanisms.
Current mechanisms of macula densa cell signalling
Authors: Komlosi P. , Fintha A. , Bell P. D.
Published: July 2004

Macula densa cells couple renal haemodynamics, glomerular filtration and renin release with tubular fluid salt and water reabsorption. These cells detect changes in tubular fluid composition through a complex of intracellular signalling events that are mediated by membrane transport pathways. Increases in luminal fluid sodium chloride concentration result in alterations in cell sodium chloride concentration, cytosolic calcium, cell pH, basolateral membrane depolarization and cell volume. Macula densa signalling then involves the production and release of specific paracrine signalling molecules at their basolateral membrane. Upon moderate increases in luminal sodium chloride concentration macula densa cells release increasing amounts of ATP and decreasing amounts of prostaglandin E2, thereby increasing afferent arteriolar tone and decreasing the release of renin from granular cells. On the other hand, further increases in luminal concentration stimulate the release of nitric oxide, which serve to prevent excessive tubuloglomerular feedback vasoconstriction. Paracrine signalling by the macula densa cells therefore controls juxtaglomerular function, renal vascular resistance and participates in the regulation of renin release.
Transgenic mice for studies of the renin–angiotensin system in hypertension
Authors: Lavoie J. L. , Bianco R. A. , Sakai K. , Keen H. L. , Ryan M. J. , Sigmund C. D.
Published: July 2004

Hypertension is a polygenic and multi‐factorial disorder that is extremely prevalent in western societies, and thus has received a great deal of attention by the research community. The renin–angiotensin system has a strong impact on the control of blood pressure both in the short‐ and long‐term, making it one of the most extensively studied physiological systems. Nevertheless, despite decades of research, the specific mechanisms implicated in its action on blood pressure and electrolyte balance, as well as its integration with other cardiovascular pathways remains incomplete. The production of transgenic models either over‐expressing or knocking‐out specific components of the renin–angiotensin system has given us a better understanding of its role in the pathogenesis of hypertension. Moreover, our attention has recently been refocused on local tissue renin–angiotensin systems and their physiological effect on blood pressure and end‐organ damage. Herein, we will review studies using genetic manipulation of animals to determine the role of the endocrine and tissue renin–angiotensin system in hypertension. We will also discuss some untraditional approaches to target the renin–angiotensin system in the kidney.
Genetic targeting of the brain renin‐angiotensin system in transgenic rats: Impact on stress‐induced renin release
Authors: Baltatu O. , Campos L. A. , Bader M.
Published: July 2004

The advance of genetic technologies to permit tissue‐specific targeted gene manipulation allowed the development of transgenic models with alterations of the renin‐angiotensin (RAS) solely in the brain. We have used such methodology to develop a transgenic rat with a brain specific alteration of the RAS [TGR(ASrAOGEN)], in order to elucidate a causative role for the brain RAS and its relevance in different pathophysiological processes. The TGR(ASrAOGEN) rats have decreased levels of angiotensinogen (AOGEN) throughout the brain because of an antisense inhibition of the astroglial AOGEN synthesis. In this review we aimed at summarizing the experience obtained from utilizing the TGR(ASrAOGEN) rat model to study the brain RAS and present novel results providing evidence for the involvement of this system in stress‐induced renin release.
Guidelines for the diagnosis and management of hereditary spherocytosis
Authors: Bolton‐Maggs P. H. B. , Stevens R. F. , Dodd N. J. , Lamont G. , Tittensor P. , King M.‐J. ,   General Haematology Task Force of the British Committee for Standards in Haematology
Published: July 2004

Hereditary spherocytosis (HS) is a heterogeneous group of disorders with regard to clinical severity, protein defects and mode of inheritance. It is relatively common in Caucasian populations; most affected individuals have mild or only moderate haemolysis. There is usually a family history, and a typical clinical and laboratory picture so that the diagnosis is often easily made without additional laboratory tests. Atypical cases may require measurement of erythrocyte membrane proteins to clarify the nature of the membrane disorder and in the absence of a family history, occasionally molecular genetic analysis will help to determine whether inheritance is recessive or non‐dominant. It is particularly important to rule out stomatocytosis where splenectomy is contraindicated because of the thrombotic risk. Mild HS can be managed without folate supplements and does not require splenectomy. Moderately and severely affected individuals are likely to benefit from splenectomy, which should be performed after the age of 6 years and with appropriate counselling about the infection risk. In all cases careful dialogue between doctor, patient and the family is essential. Laparoscopic surgery, when performed by experienced surgeons, can result in a shorter hospital stay and less pain.
High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation
Authors: Nilsson Therese , Lenhoff Stig , Rylander Lars , Höglund Mattias , Turesson Ingemar , Mitelman Felix , Westin Jan , Johansson Bertil
Published: July 2004

Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non‐neoplastic cells are more prone to divide in culture than neoplastic cells. Direct chromosome preparations (DCP) would be one way to circumvent this methodological problem. We have investigated 47 bone marrow samples from 39 patients by DCP. A median of 58 metaphases (range 9–158) was analysed per sample. Interphase FISH analyses using probes to detect IGH rearrangements, ‐13/13q‐, +3, +7, and +11 were also performed. Abnormal karyotypes were detected in 15 (63%) of 24 MM and in 4 (50%) of eight MGUS/smouldering MM (SMM) cases that could be successfully cytogenetically analysed. Age, sex, or degree of bone marrow plasma cell (PC) infiltration did not influence the karyotypic patterns (P > 0·05). However, the frequencies of aberrant karyotypes varied in relation to the Colcemide concentrations used – 7% (30 ng/ml) versus 69% and 67% (100 and 200 ng/ml, respectively) (P = 0·01). Combining the G‐banding and FISH results, abnormalities were detected in 29 of 31 (94%) MM and in six of eight (75%) MGUS/SMM patients. Thus, cytogenetic and FISH analyses after DCP using 100–200 ng Colcemide/ml identified aberrations in most MM/MGUS/SMM, irrespective of PC percentages.
Tolerance associated with cord blood transplantation may depend on the state of host dendritic cells
Authors: Liu Enmei , Law Helen K. W. , Lau Yu‐Lung
Published: July 2004

Allogeneic cord blood (CB) transplantation is associated with less severe graft‐versus‐host disease (GvHD), thought to be due to the immaturity of CB T cells, but how T cells interact with host and donor‐derived dendritic cells (DCs) to initiate GvHD has not been elucidated. We therefore investigated the responses of CB and adult blood CD4+ T cells co‐cultured with adult host DCs of different maturities. Primed by adult host DCs, CB and adult blood CD4+ T cells underwent similar changes in the expression of CD45RA/45RO, CD25, CD40L and CTLA‐4. However, CB CD4+ T cells, when primed by either immature or Bacillus Calmette‐Guerin mycobacteria‐treated adult host DCs, produced lower interferon‐γ (IFN‐γ) and higher interleukin‐10 (IL‐10), which is a regulatory T cell‐like cytokine profile, as compared with adult blood CD4+ T cells. In contrast, lipopolysaccharide (LPS)‐treated adult host DCs significantly up‐regulated IFN‐γ and down‐regulated IL‐10 production levels from CB CD4+ T cells to that from adult blood CD4+ T cells. The sustained low IFN‐γ and high IL‐10 production from CB CD4+ T cells co‐cultured with adult blood DCs might account for the less severe GvHD occurrence after CB transplantation, which could be reversed by LPS‐treated adult blood DCs.
Low expression of the putative tumour suppressor gene gravin in chronic myeloid leukaemia, myelodysplastic syndromes and acute myeloid leukaemia
Authors: Boultwood Jacqueline , Pellagatti Andrea , Watkins Fiona , Campbell Lisa J. , Esoof Noor , Cross Nicholas C. P. , Eagleton Helen , Littlewood Tim J. , Fidler Carrie , Wainscoat James S.
Published: July 2004

The putative tumour suppressor gene gravin is down‐regulated in several solid tumours and is implicated in tumorigenesis. We have evaluated the expression levels of the gravin gene in the CD34+/blast cells of a range of myeloid malignancies as compared with controls using real‐time quantitative polymerase chain reaction (PCR). Gravin was markedly down‐regulated in 41 of 41 patients with acute myeloid leukaemia (AML), nine of 10 patients with myelodysplastic syndromes (MDS) and 33 of 33 patients with chronic myeloid leukaemia (CML), of whom 24 were in blast crisis (BC). We have shown that gravin is consistently down‐regulated in the CD34+/blast cells of myeloid malignancies and may play a role in the molecular pathogenesis of these disorders.