Cerebral Nervous System Research Articles

Abstract WMP55: Vessel Wall Characteristics using High Resolution Magnetic Resonance Imaging in Reversible Cerebral Vasoconstriction Syndrome and Central Nervous System Vasculitis

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) and central nervous system (CNS) vasculitis often have similar initial clinical presentation, laboratory findings and imaging features creating a diagnostic dilemma. High-resolution-3-Tesla Magnetic Resonance Imaging with Gadolinium contrast (HR-MRI) is a non-invasive method to look at intracranial vessel wall characteristics. Methods: A retrospective analysis of all patients with a diagnosis of RCVS or CNS vasculitis that underwent HR-MRI at our institution was performed. Inclusion criteria for RCVS were clinical presentation, no aneurysmal subarachnoid hemorrhage, normal cerebrospinal fluid and reversible multifocal intracranial vessel stenosis whereas criteria for CNS vasculitis were cases with positive brain biopsy or typical clinical presentation, course and laboratory markers with rheumatology and stroke neurology agreement in diagnosis. Demographics, clinical presentation, laboratory testing, imaging studies and outcomes were collected. Results: Eleven patients with RCVS [10 (90.9%) females, mean age 45.2] and 8 with CNS vasculitis [6 primary CNS vasculitis, 6 (75%) males, mean age 43.5] were included in the study. No abnormal vessel wall enhancement or thickening was seen in any of the RCVS patients in areas of vessel stenosis. Six (75%) of CNS vasculitis patients had vessel wall thickening or enhancement (p=0.001 for comparison to RCVS) and the remaining 2 patients had HR-MRI performed 6 and 10 years after diagnosis and chronic treatment. All RCVS patients who had follow up HR-MRI demonstrated resolution of the multifocal stenosis. Two out of 4 CNS vasculitis patients with subsequent HR-MRI imaging had decrease in vessel wall thickening and enhancement after immunosuppressive therapy. Conclusion: In acute stages of presentation, HR-MRI may be useful in differentiating RCVS from CNS vasculitis. It may also be useful in following the disease course to look for resolution of intracranial vessel stenosis in RCVS or treatment response in vasculitis. Further studies are needed to confirm the utility of HR-MRI in diagnosis and disease progression in RCVS and vasculitis.

Cutaneous γδ T-cell Lymphomas

We reviewed our multicenter experience with gamma-delta (γδ) T-cell lymphomas first presenting in the skin. Fifty-three subjects with a median age of 61 years (range, 25 to 91 y) were diagnosed with this disorder. The median duration of the skin lesions at presentation was 1.25 years (range, 1 mo to 20 y). The most common presentation was deep plaques (38 cases) often resembling a panniculitis, followed by patches resembling psoriasis or mycosis fungoides (10 cases). These lesions tended to ulcerate overtime (27 cases). Single lesions or localized areas of involvement resembling cellulitis or pyoderma were reported in 8 cases. The most common anatomic site of involvement was the legs (40 cases), followed by the torso (30 cases) and arms (28 cases). Constitutional symptoms were reported in 54% (25/46) of the patients, including some with limited skin involvement. Significant comorbidities included autoimmunity (12 cases), other lymphoproliferative disorders (5 cases), internal carcinomas (4 cases), and viral hepatitis (2 cases). Lymphadenopathy (3/42 cases) and bone marrow involvement (5/28 cases) were uncommon, but serum lactose dehydrogenase (LDH) was elevated in 55% (22/39) of the patients. Abnormal positron emission tomography and/or computed tomography scans in 20/37 subjects mostly highlighted soft tissue or lymph nodes. Disease progression was associated with extensive ulcerated lesions resulting in 27 deaths including complications of hemophagocytic syndrome (4) and cerebral nervous system involvement (3). Median survival time from diagnosis was 31 months. Skin biopsies varied from a pagetoid pattern to purely dermal or panniculitic infiltrates composed of intermediate-sized lymphocytes with tissue evidence of cytotoxicity. The most common immunophenotype was CD3+/CD4⁻/CD5⁻/CD8⁻/BF1⁻/γ-M1+/TIA-1+/granzyme-B+/CD45RA-/CD7-, and 4 cases were Epstein-Barr virus positive. This is the largest study to date of cutaneous γδ T-cell lymphomas and demonstrates a variety of clinical and pathologic presentations with a predictable poor outcome.

Human Skin Hypoxia Modulates Cerebrovascular and Autonomic Functions

Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor.

Atherosclerotic Renal Artery Stenosis, the Oculostenotic Reflex, and Therapeutic Nihilism

Fifteen years ago, Topol and Nissen1 described the oculostenotic reflex as an “irresistible temptation … to perform angioplasty on any significant residual stenosis,” highlighting a widely held misperception that an angiographically severe stenosis must cause ischemia and that revascularization results in clinical benefit. Although quantitative angiography improves the accuracy of stenosis severity, it does not improve the accuracy of diagnosing ischemia. In fact, more than one third of angiographically severe coronary stenoses are hemodynamically insignificant by fractional flow reserve (FFR), and FFR results are highly correlated with findings of ischemia by myocardial perfusion imaging.2 Similarly, angiographic renal artery stenosis (RAS) severity correlates poorly with hemodynamic significance.3 Article see p 537 Five randomized trials4–8 demonstrated that a strategy of renal revascularization based on the oculostenotic reflex was not associated with improvement in blood pressure or renal function or reduction in clinical events compared to medical therapy alone. These results lead some to recommend a nihilistic approach …

A Wasp Manipulates Neuronal Activity in the Sub-Esophageal Ganglion to Decrease the Drive for Walking in Its Cockroach Prey

BackgroundThe parasitoid Jewel Wasp hunts cockroaches to serve as a live food supply for its offspring. The wasp stings the cockroach in the head and delivers a cocktail of neurotoxins directly inside the prey's cerebral ganglia. Although not paralyzed, the stung cockroach becomes a living yet docile ‘zombie’, incapable of self-initiating spontaneous or evoked walking. We show here that such neuro-chemical manipulation can be attributed to decreased neuronal activity in a small region of the cockroach cerebral nervous system, the sub-esophageal ganglion (SEG). A decrease in descending permissive inputs from this ganglion to thoracic central pattern generators decreases the propensity for walking-related behaviors.Methodology and Principal FindingsWe have used behavioral, neuro-pharmacological and electrophysiological methods to show that: (1) Surgically removing the cockroach SEG prior to wasp stinging prolongs the duration of the sting 5-fold, suggesting that the wasp actively targets the SEG during the stinging sequence; (2) injecting a sodium channel blocker, procaine, into the SEG of non-stung cockroaches reversibly decreases spontaneous and evoked walking, suggesting that the SEG plays an important role in the up-regulation of locomotion; (3) artificial focal injection of crude milked venom into the SEG of non-stung cockroaches decreases spontaneous and evoked walking, as seen with naturally-stung cockroaches; and (4) spontaneous and evoked neuronal spiking activity in the SEG, recorded with an extracellular bipolar microelectrode, is markedly decreased in stung cockroaches versus non-stung controls.Conclusions and SignificanceWe have identified the neuronal substrate responsible for the venom-induced manipulation of the cockroach's drive for walking. Our data strongly support previous findings suggesting a critical and permissive role for the SEG in the regulation of locomotion in insects. By injecting a venom cocktail directly into the SEG, the parasitoid Jewel Wasp selectively manipulates the cockroach's motivation to initiate walking without interfering with other non-related behaviors.

Thrombose veineuse cérébrale et polyradiculonévrite aiguë révélant un lupus érythémateux disséminé

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. In 40% of cases, lupus can be revealed by neurological symptoms. Cerebral nervous system complications predominate and can be a negative factor for prognosis. Peripheral features are rare and various and can compromise functional prognosis, sometimes with fatal outcome. We report the case of a 30-year-old woman who presented a cerebral venous thrombosis of the superior longitudinal sinus. Outcome was favorable with antibiotics and anticoagulants. Four months later, she developed an acute polyradiculoneuritis associated with an inflammatory syndrome and positive tests for antinuclear antibody and antinuclear anti-DNA. The diagnosis of neurolupus was retained on the basis of four criteria of the American college of Rheumatology. The patient was given steroid therapy associated with a course of intravenous immunoglobulin. She has fully recovered her deficit. Cerebral venous thrombosis and acute polyradiculonévrites are rare events in systemic lupus erythematosus. Early diagnosis and management are crucial.

Activity of Pemetrexed on brain metastases from Non-Small Cell Lung Cancer

Brain metastases from Non-Small Cell Lung Cancer are usually associated with poor prognosis and up to now chemotherapy has shown a modest activity upon cerebral localizations. We investigated the role of Pemetrexed, a new, well tolerated multi-target antifolate, on brain metastases. Patients and methods We collected 39 patients with evidence of cerebral nervous system (CNS) localizations from Non-Small Cell Lung Cancer (NSCLC) before starting treatment with Pemetrexed as second-line or further-line therapy. Results We confirmed the good tolerability of Pemetrexed even in that setting of patients and we reported a progressive disease (PD) in 12 patients (30.8%), a stable disease (SD) and partial response (PR) in 12 (30.8%) and 15 (38.4%) patients respectively, with an overall clinical benefit obtained in 69% of patients. The cerebral response to Pemetrexed was interesting with a cerebral radiological benefit obtained in 32 patients (82%), while 7 patients only showed brain progressive disease. Overall median survival was 10 months. All irradiation-naïve patients and those with clear radiological evidence of cerebral progression after brain radiotherapy and before Pemetrexed, overall 22 patients, were included in one group, in order to avoid overlapping effects between brain radiotherapy and Pemetrexed over CNS localizations. Within that setting, we demonstrated an overall clinical benefit (SD + PR) and cerebral benefit in 63% and 68%, of patients respectively. Distribution of patients by overall response to Pemetrexed and CNS response was highly suggestive of activity of Pemetrexed on brain metastases. Conclusion We demonstrated the good tolerability of Pemetrexed even in patients with advanced NSCLC and brain metastases, and we found a very good overall response rate with evidence of activity on brain localizations.

Recommendations for the treatment of established fungal infections

Evidence-based guidelines for the treatment of established fungal infections in the adult haematology/oncology setting were developed by a national consensus working group representing clinicians, pharmacists and microbiologists. These updated guidelines replace the previous guidelines published in the Internal Medicine Journal by Slavin et al. in 2004. The guidelines are pathogen-specific and cover the treatment of the most common fungal infections including candidiasis, aspergillosis, cryptococcosis, zygomycosis, fusariosis, scedosporiosis, and dermatophytosis. Recommendations are provided for management of refractory disease or salvage therapies, and special sites of infections such as the cerebral nervous system and the eye. Because of the widespread use newer broad-spectrum triazoles in prophylaxis and empiric therapy, these guidelines should be implemented in concert with the updated prophylaxis and empiric therapy guidelines published by this group.

Effects of N-nitrosofenfluramine, a component of Chinese dietary supplement for weight loss, on CD-1 mice

Many cases of hepatopathy including deaths have frequently occurred after ingestion of Chinese dietary supplements for weight loss containing N-nitrosofenfluramine (N-fen), a nitroso derivative of fenfluramine (Fen), which was used for the treatment of obesity in the United States. Since Fen decreases appetite by decreasing the serotonin level and exhibits an antibiotic effect, N-fen may have been added, expecting a similar effect. Thus, we synthesized N-fen and orally administered it to mice, and investigated its effect on the liver as well as on the cerebral serotonin nervous system to investigate whether N-fen exhibits an anorectic effect. Three doses of N-fen were orally administered once daily to mice for 1 week. No significant changes in body weight, food intake, and general condition were noted. The liver and kidney weights were significantly increased. On blood chemistry, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities were increased, and total bilirubin and albumin were slightly decreased. On histopathological examination, acidophilic changes and mild cellular swelling were noted in the liver. The liver drug-metabolizing enzyme (P-450) level was significantly higher. The effect of N-fen on the serotonin (5HT) nervous system was examined by quantitative autoradiography of the mouse brain, and it was found that N-fen did not decrease the 5HT nerve activity. Effects of reuptake and release of monoamine neurotransmitters [dopamine (DA), 5HT, and norepinephrine (NE)] were investigated. N-fen inhibited a little 5HT reuptake, and did not inhibit reuptakes of DA and NE. Moreover, N-fen did not affect release of the three monoamines. The above findings suggested that N-fen did not exhibit a serotonin nerve fiber-mediated anorectic effect in mice, but induced hepatopathy.

Molecular Analysis of Immunoglobulin Genes in Primary Intraocular Lymphoma

To analyze somatic hypermutations in clonally rearranged IgH chain variable (V) genes of primary intraocular lymphoma (PIOL), to identify the differentiation stage of B-PIOL cells. Sixteen cases of PIOL were diagnosed on the basis of morphology and immunohistology. In six patients, simultaneous cerebral lymphomatous involvement was known; stereotactic biopsy specimens were investigated in three cases. A polymerase chain reaction (PCR) was performed on DNA extracted from vitrectomy specimens or from paraffin-embedded sections, to amplify the clonally rearranged heavy-chain immunoglobulin (IgH) genes. The isolated PCR products were sequenced and compared with published VH germ-line segments to determine the VH usage and number of somatic mutations in the complementarity-determining region (CDR)2 and framework region (FR)3. All tumors exhibited clonal IgH rearrangements. Of the eight sequenceable cases, four had the VH4-34 gene segment, two the VH3-23, one the VH3-7, and another the VH3-30. The pattern of somatic mutations indicated selection of PIOL cells for expression of a functional antibody. The mean frequency of somatic mutations detected for the IgH gene was very high (14.5%). In three oculocerebral lymphomas, the identical B-cell clone was demonstrated in ocular and cerebral tissues. The data suggest that PIOLs (1) are derived from mature B-cells that have undergone the germinal center reaction and (2) are closely related to primary cerebral nervous system lymphoma (PCNSL), due to their high mutation frequency of VH region genes. The close relationship between PIOL and PCNSL is underlined by demonstration of the same VH segment (VH4-34) in three of six cases of oculocerebral lymphoma.

143 Estrogen Attenuates Oligodendrocyte Apoptosis Caused by Hyperoxia

Background: In the developing human brain, periventricular leukomalacia (PVL) is the predominant white matter injury underlying the development of cerebral palsy. Our group recently showed that a rise of oxygen tissue tension is a powerful trigger to initiate apoptosis in premature and immature, but not in mature oligodendrocytes (OL). Estrogen plays an important role in the development and function of the cerebral nervous system, and estrogen receptors show a specific distribution with high density arround the third ventricle, the region where OL progenitors are generated. We therefore examined the effects of estrogen on hyperoxia-induced cell death in cultured rat immature oligodendroglia cells. Methods: OLN-93 cells, derived from spontaneously transformed cells of 5- to 10-day-old primary rat brain oligodendrocytes were subjected to 24–72 h of hyperoxia (80% O2) in the presence or absence of estrogen (17beta-estradiol) at various concentrations. These immature oligodendrocytes resemble an intermediate stage between oligodendrocyte precursors and mature oligodendrocytes. Flow cytometry was used to assess apoptosis via annexin-V, anti-activated caspase-3 antibody, and propidium iodide staining. Oligodendrocyte maturation status and caspase-3 activation were confirmed by immunochemistry. Results: In immature rat oligodendrocytes (OLN-93), apoptosis was detected at various stages (early: annexin-V, effector: caspase-3) after 24–72 h of hyperoxia (80% O2). Cell death was reduced up to 30% by preincubation with estrogen at a concentration optimum of 10–7 M estrogen. Conclusion: Estrogen reduces apoptosis in immature oligodendrocytes exposed to hyperoxia. The sudden drop in circulating estrogen of placental origin after mammalian birth may aggravate the susceptibility of immature oligodendrocytes to increased oxygen tension. Supported by grants from the German Federal Department of Education and Research (BMBF, # 01 ZZ 0101), Bonn, and the Ernst Schering Research Foundation, Berlin.

Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features

Primary intraocular lymphoma (PIOL) is a rare non-Hodgkin lymphoma which arises in the retina or the vitreous. It can occur either together with or independently of primary cerebral nervous system lymphoma (PCNSL); the incidence of the latter has significantly increased over the past three decades. PIOL remains one of the most difficult diagnoses to establish, particularly due to its ability to mimic other diseases in the eye and to the limited material which is often available for examination. The article reviews the clinical, histopathological, molecular biological and biochemical approaches to the diagnosis of PIOL. The differential diagnoses, including other lymphomatous manifestations in the eye, e.g. primary uveal lymphoma, as well as non-neoplastic uveal diseases are addressed. Furthermore, the treatment strategies for PIOL are summarised. Diagnostic progress has been made in various fields, including flow cytometry and immunocytology, cytokine analysis, and as well as molecular biological analysis of the immunoglobulin heavy and light chains using polymerase chain reaction on both fixed and non-fixed material. The optimal therapy of PIOL remains to be determined: the current trends suggest that combined radiotherapy and chemotherapy, as well as intravitreal chemotherapy, are of value. Novel therapies which may have a role in the future include oral trofosfamide. Our understanding of the pathogenesis of PIOL/PCNSL remains far from complete. Intensified efforts must be made to determine the cell of origin of PIOL, as well as to establish "molecular signatures", which could be used to decrease diagnostic delay. Further studies, possibly prospective ones, are required to establish the optimal therapy for initial and recurrent disease.

The development of the serotonergic and FMRF-amidergic nervous system in Antalis entalis (Mollusca, Scaphopoda)

The morphogenesis of serotonin- and FMRF-amide-bearing neuronal elements in the scaphopod Antalis entalis was investigated by means of antibody staining and confocal laser scanning microscopy. Nervous system development starts with the establishment of two initial, flask-like, serotonergic central cells of the larval apical organ. Slightly later, the apical organ contains four serotonergic central cells which are interconnected with two lateral serotonergic cells via lateral nerve projections. At the same time the anlage of the adult FMRF-amide-positive cerebral nervous system starts at the base of the apical organ. Subsequently, the entire neuronal complex migrates behind the prototroch and the six larval serotonergic cells lose transmitter expression prior to metamorphic competence. There are no strictly larval FMRF-amide-positive neuronal structures. The development of major adult FMRF-amide-containing components such as the cerebral system, the visceral loop, and the buccal nerve cords, however, starts before the onset of metamorphosis. The anlage of the putative cerebral system is the only site of adult serotonin expression in Antalis larvae. Establishment of the adult FMRF-amidergic and serotonergic neuronal bauplan proceeds rapidly after metamorphosis. Neurogenesis reflects the general observation that the larval phase and the expression of distinct larval morphological features are less pronounced in Scaphopoda than in Gastropoda or Bivalvia. The degeneration of the entire larval apical organ before metamorphic competence argues against an involvement of this sensory system in scaphopod metamorphosis. The lack of data on the neurogenesis in the aplacophoran taxa prevent a final conclusion regarding the plesiomorphic condition in the Mollusca. Nevertheless, the results presented herein shed doubts on general theories regarding possible functions of larval "apical organs" of Lophotrochozoa or even Metazoa.

A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature.

The mechanisms mediating leukocyte recruitment into the cerebral nervous system during inflammation are still poorly understood. The objective of this study was to investigate the leukocyte recruitment in the brain microcirculation by intravital microscopy. Superfusion of the brain with artificial cerebrospinal fluid did not induce leukocyte rolling or adhesion. However, intraperitoneal tumor necrosis factor-alpha (TNF-alpha) caused marked leukocyte rolling and adhesion in the brain microcirculation. Histology revealed that the recruitment was primarily of neutrophils. Both E- and P-selectin were required for TNF-alpha-induced leukocyte recruitment, as rolling was reduced after treatment with either anti-E- or anti-P-selectin antibody and eliminated in E- or P-selectin-deficient mice. A significant increase in brain P- and E-selectin expression was seen after TNF-alpha treatment, but both were an order of magnitude less than in any other tissue. We observed significant platelet paving of TNF-alpha-stimulated endothelium and found that anti-platelet antibody reduced leukocyte rolling and adhesion, as did acetylsalicylic acid (aspirin). However, depletion of platelets did not reduce cerebral P-selectin expression. Moreover, chimeric mice lacking P-selectin on endothelium but not platelets had significantly decreased P-selectin expression and reduced leukocyte recruitment in the brain. This suggests a role for endothelial P-selectin in cerebral leukocyte recruitment. In conclusion, TNF-alpha-induced neutrophil recruitment into the brain requires both endothelial E-selectin and P-selectin as well as platelets, but platelet P-selectin was not a major contributor to this process.

Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats.

Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.

3L1415 ホヤ幼生の脳神経系で特異的に発現しているGタンパク質遺伝子

3L1415 ホヤ幼生の脳神経系で特異的に発現しているGタンパク質遺伝子

Neurosyphilis in an eight-year-old child: Usefulness of the SPECT study

An 8-year-old boy with symptomatic late-onset congenital syphilis is reported. The child had been undertreated when he was 78 days of age, but his clinical and serologic follow-up did not occur until he was 3 years of age. At that time, he was asymptomatic, and cerebrospinal fluid disclosed not only hypercellularity but also a reactive Venereal Disease Research Laboratories test. Although he was then retreated at 4 years of age, he developed seizures. Cranial computed tomography scans and magnetic resonance imaging were normal, but two single photon emission computed tomography scans performed when he was 5 years of age and then 7 years of age demonstrated areas of hypoperfusion that closely agreed with the alterations on electroencephalograph. Brain single photon emission computed tomography was able to detect cerebral nervous system abnormalities in this young patient with neurosyphilis, whereas other image studies did not.

Late effects of ionizing radiations on central nervous system, spinal cord and peripheral nerves

Despite the lack of characteristic features, demyelination is the dominant feature of radiation induced late effects observed in cerebral nervous system and spinal cord. Acute, subacute and chronic changes are described in terms of pathological, clinical and radiological observations. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, while imaging changes are observed with lower doses. The most widely observed dose limit for the spinal cord is 45 Gy, in the absence of dose modifying chemotherapy. Tumor progression may be hard to distinguish from radiochemotherapy effects. The potential protective role of hyperfractionation is not yet clearly established. Peripheral nerves late effects, although rare, are described.

Ueda Method of the Treatment for Patients with Motor Disturbance in Disease of Cerebral Nervous System

Ueda Method of the Treatment for Patients with Motor Disturbance in Disease of Cerebral Nervous System

A mosquito neuropeptide in a moth larva ( Helicoverpa zea): Relation to FMRF-amide immunoreactivity

The cerebral nervous and midgul endocrine systems of the larval corn earworm, Helicoverpa zea, were examined using light microscopy and immunocytochemistry for RF-amide family peptides. Immunoreactivity for a mosquito neuropeptide, Aedes Head Peptide-I (Aea-HP-I, pERPhPSLKTRFa), is widely distributed in this lepidopteran. Immunostaining for Aea-HP-I is localized (1a) in perikarya and axons of the brain, the subesophageal ganglion, and the first thoracic ganglion, (b) in peripheral axons innervating muscles of the midgut, and (2) in numerous midgut endocrine cells. Aea-HP-I-associated activity generally occurs as a subset of FMRF-amide (FMRFa; a molluscan cardioactive peptide) immunoreactivity. Crossreactivity studies indicate that Aca-HP-I and FMRFa immunoreactivities are heterogeneous in the cerebral nervous system and in axons innervating the muscles of the midgut, but may be homogeneous in midgut endocrine cells. Radiommunoassay for Aea-HP-I reveals immunoreactivity in hemolymph, as well as in extracts of midguts and heads.