First manifestation of lambda positive plasmacytoma in the orbital apex with acute unilateral loss of vision.

INTRODUCTION: An intracranial plasmacytoma is a rare form, which can involve the calvarium, dura or the cranial base. Only few case reports describe the manifestation of plasmacytoma of the skull base with affection of visual acuity. CASE REPORT: We describe the case of a 43-year-old woman, presenting with an acute unilateral loss of vision. The presumption diagnosis was retrobulbar neuritis as first manifestation of multiple sclerosis. MR imaging disclosed a tumour in the left orbital region and a meningioma was suspected. After complete resection with decompression of the optic nerve, the neuropathological examination revealed a lambda positive plasmacytoma. Additional work-up disclosed an involvement of multiple vertebral bodies. Due to the diagnosis of multiple myeloma, oncological therapy had been initiated. CONCLUSION: Skull base plasmacytoma is a rare disease. Solitary lesions causing neurological deficits should be treated aggressively including surgery for histological diagnosis and decompression of neural structures. Prognosis and further therapy depends on the systemic stage of disease, which has to be defined by diagnostic work-up.

Progressive biological behavior of a dysembryoplastic neuroepithelial tumor.

We present the case of a 13-month-old girl with a right occipital cortical alteration on MRI that proved to be a growing lesion. Tumor growth had been observed over a period of 15 months before total resection was performed, revealing a dysembryoplastic neuroepithelial tumor WHO grade I. This case shows that dysembryoplastic neuroepithelial tumors can present as growing neoplasias. It underlines the importance of obtaining histologic diagnosis and close follow-up examinations using MRI, even in so-called stable lesions that are only unveiling through epileptic seizures.

Molecular characterization of signalling pathways in cancer stem cells.

To avoid artefacts introduced by culturing cells for extended periods of time, it is crucial to use low-passage patient-derived tumour cells. The ability to enrich, isolate and assay sub-populations of cells that behave as cancer stem cells (CSCs) from these primary cell lines is essential before performing characterizations such as gene-expression profiling. We have isolated cells from glioblastomas which show characteristics of CSCs. Although glioblastomas contain only a relatively small amount of putative CSCs, these cells express many genes which seem to be worthy targets for future therapies.

[Cervical myelopathy in a newborn with achondroplasia]. / Diagnostik der zervikalen Myelopathie bei einem Neugeborenen mit Achondroplasie.

BACKGROUND: Patients with achondroplasia have an increased risk of apnoea due to cervical myelopathy. The indication for operative decompression can not be made by MRI alone, because signal alteration and osseous compression of the cervico-medullary region without functional relevance are frequent in this disease. CASE REPORT: We report on a male new-born with achondroplasia who displayed apnoeas from the first day of life. Two times, mask ventilation had to be performed. After exclusion of other diseases potentially causing apnoeas, an MRI of the skull and cervical spine revealed cervico-medullary compression due to foramen magnum stenosis, but no signal alterations of brain stem and cervical mark. Recording of somato-sensory evoked potentials (SSEP) of the median nerve showed normal potentials at Erb's point. By contrast, cortical potentials were distinctly abnormal during left-sided stimulation and could not be recorded during right-sided stimulation. Based on these findings, operative decompression of the craniocervical region was performed which led immediately to complete remission of clinical symptoms. At follow-up, MRI revealed a normal width of the foramen magnum and SSEP were markedly improved. CONCLUSION: In newborns with Achondroplasia, SSEP can confirm the functional relevance of osseous compression of the cervico-medullary region, and facilitate the decision for operative decompression.

Real-time integration of ultrasound into neuronavigation: technical accuracy using a light-emitting-diode-based navigation system.

BACKGROUND: In brain surgery, intraoperative brain deformation is the major source of postimaging inaccuracy of neuronavigation. For intraoperative imaging of brain deformation, we developed a platform for the integration of ultrasound imaging into a navigation system. METHOD: A commercially available ultrasound system was linked to a light-emitting-diode- (LED) based neuronavigation system via rigid fixation of a position localiser to the ultrasound probe and ultrasound image transfer into the navigation system via a S-VHS port. Since the position of the ultrasound image co-ordinate system is not readily defined within the navigation reference co-ordinate system (REF CS), a transformation which links both co-ordinate systems has to be defined by a calibration procedure. Calibration of the ultrasound probe within the REF CS was performed via a cross-wire phantom. The phantom target was defined within the navigation co-ordinate system (by pointer under microscopic control) and imaged by ultrasound. Ultrasound presets were optimised (digital beam focusing, gain intensity) to attain a small echoic target for manual target definition. The transformation was derived from 150 ultrasound measures and iteration. Accuracy was calculated as mean linear error (LE; in X(REF), Y(REF), or Z(REF) direction), overall mean LE (linear errors of all axes X(REF) to Z(REF)) and Euclidean error (EE; vectorial distance from the physical target). FINDINGS: Optimised ultrasound presets (8 MHz frequency, digital beam focusing, 20% gain intensity) enabled a low interobserver error (mean: 0.5 mm, SD: 0.28) for target definition within the 2-D ultrasound image. Mean accuracy of pointer-based physical target definition in the REF CS was 0.7 mm (RMSE; SD: 0.23 mm). For navigated ultrasound, the overall mean LE was 0.43 mm (SD: 1.36 mm; 95%CL: 3.13 mm) with a mean EE of 2.26 mm (SD: 0.97 mm; 95%CL: 4.21 mm). INTERPRETATION: Using a single target cross-wire phantom, a highly accurate integration of ultrasound imaging into neuronavigation was achieved. The phantom accuracy of integration lies within the range of application accuracy of navigation systems and warrants clinical studies.

Comparison of different life-cycle impact assessment methods for aquatic ecotoxicity.

Human and ecotoxicity impact categories are problematic to quantify within life-cycle impact assessment (LCIA) because their local scope makes them difficult to aggregate with the traditional global-impact categories used in life-cycle assessment (LCA). For being able to assess local impacts such as toxicity, LCIA developers increasingly include fate modeling into LCA. This article follows this development by comparing different LCIA methods for aquatic ecotoxicology and by investigating the importance of fate within LCIA, the necessity of considering freshwater and seawater compartments separately, and the key degradation and intermedia transfer processes involved. The methods are compared by assessing an example study of domestic clothes washing in former West Germany. Four LCIA methods are selected and applied to four substances emitted during the washing process. The conclusion is that the consideration of environmental fate does matter and that aquatic ecotoxic impacts can differ significantly for the same substance in freshwater and in marine ecosystems. The way (bio)degradation, photolysis, volatilization, and transfer from agricultural soils are considered plays an important role as do the system boundaries chosen. This means that the LCIA methodology should remain flexible so that appropriate methods can be chosen for different applications. Fate models being developed in the environmental risk assessment of chemicals can contribute to the further improvement of LCIA methods.

[Delayed traumatic CSF-fistulas: a retrospective analysis]. / Verzögernd auftretende Liquorfisteln - eine retrospektive Analyse.

Immediate posttraumatic CSF-fistulas are a well known entity after severe head injury. Delayed onset of rhinorrhea is considered to be rare. In the last 5 years 7 patients were treated in our department, who developed rhinorrhea 2-25 years after trauma. All patients went through episodes of meningitis. In 4 cases intermittent rhinorrhea was reported. In all cases a bony defect of the anterior skull base was detected by coronal bone window CT-scan. In three of them an encephalocele was revealed by MR-scanning. Treatment consisted in reconstruction of anterior skull base with a pedicled galeal-pericranial flap via a bifrontal craniotomy and went out without any complications. Delayed rhinorrhea after severe head injury is not a rare curiosity. In cases of bony defects after head injury reconstruction of anterior skull base is recommended to prevent episodes of recurrent meningitis.

Boswellic acids inhibit glioma growth: a new treatment option?

Conventional malignant glioma therapy (surgery, radiation therapy and chemotherapy) does not yield satisfying results. The prognosis of the glioma patient depends more on the histological grading of the tumor and patient's age than on the therapy. Especially the adjuvant chemotherapy failed to date to influence survival time in glioma patients significantly. To improve results in malignant glioma therapy additional therapeutic regimes are necessary. In an earlier study we were able to show a significant reduction on perifocal edema by an extract from gum resin (EGR) accompanied with a clinical improvement in patients with malignant glioma. Also a decrease of urinary LTE4-excretion as a metabolite of leukotriene synthesis in brain tumors was observed. Furthermore we had found a proliferation inhibiting activity of the extract form EGR, the boswellic acids in cell cultures. The purpose of this experimental study was to elucidate the effects of the boswellic acids, which are constituents of an extract from gum resin on tumor growth in vivo. Female wistar rats weighing 200-250 g were treated with the drug 14 days after inoculation of C6 tumor cells into their right caudate nucleus and randomization into 4 groups. The treatment groups received different dosages and were compared to a control group without any additional treatment. Survival time of the rats in the highest dosage group (3 x 240 mg/kg body weight) was more than twice as long as in the control group (P < 0.05). In a second experiment the inhibition of tumor cell proliferation was examined. The C6 tumor cells were implanted into the caudate nucleus. Drug treatment was started immediately after implantation and stopped after 14 days. The animals were sacrificed and the brains were examined microscopically. Comparing low and high dosage of EGR treatment a significant difference in tumor volume was detected (P < 0.05). The proportion of apoptotic tumor cells in animals with high dose treatment was significantly larger than in the low dose (treatment) group (P < 0.05). These data demonstrate an influence of EGR in rat glioma growth and might represent a new therapeutic option on glioma treatment in man in future. Further experimental work on human gliomas is needed to definitively answer this question.

Microvascular decompression as treatment of trigeminal neuralgia in the elderly patient.

Elderly patients with idiopathic trigeminal neuralgia are commonly referred to percutaneous treatment if medical therapy has failed. Due to elaborated microsurgical techniques and perioperative care, minimal invasive neurosurgical operations like microvascular decompression (MVD) can be offered increasingly to elderly patients. We operated upon 8 elderly patients (median 70.5 years) suffering from trigeminal neuralgia using MVD in a one-year period (1995). Seven patients were free of pain at release. At a two year follow-up, 2 patients reported of slight dull pain in the trigeminal area, one of these had been pretreated with retrogasserian glycerol rhizolysis and an initial MVD procedure four years before this decompression. All patients were still off medication (analgetics and anticonvulsants), indicating that all patients experienced an excellent (6/8) or a good (2/8) result two years after MVD. One CSF fistula requiring reoperation was the only complication. After failure of medical therapy for symptomatic trigeminal neuralgia, we encourage elderly patients to undergo MVD if the general medical condition is stable and complete pain relief without medication is the requested aim of treatment.

Postoperative headache after the lateral suboccipital approach: craniotomy versus craniectomy.

The lateral suboccipital approach to the cerebellopontine angle is typically performed as a small craniectomy. Incisional pain and headache following cerebellopontine angle surgery have been reported. Adherence of the cervical muscles to the dura, which is richly innervated, with consequent traction has been suggested to be responsible for postoperative headache. Therefore, postoperative headache probably could be reduced by replacing the bone flap between the muscles and the dura. In a prospective non-randomized study this hypothesis was tested by comparing craniectomy and craniotomy. 40 patients underwent removal of an acoustic neuroma via the retrosigmoid approach. Patients with a history of migraine, with additional intracerebral tumors or recurrencies as well as patients who developed a CSF fistula postoperatively were excluded. 29 patients were eligible for further evaluation. 13 patients underwent a craniotomy, 16 patients a craniectomy. All patients were subject to a standardized telephone interview three months and one year after surgery. Comparing the craniotomy group to the craniectomy group no difference was observed regarding age, sex, tumor size and duration of operation. 3 months as well as 12 months postoperatively headache was significantly (p < 0.05) less frequent in the craniotomy group as compared to the craniectomy group. In conclusion, an osteoplastic craniotomy significantly reduces postoperative headache and is therefore highly recommended.

Somatosensory evoked potential monitoring during positioning of the patient for posterior fossa surgery in the semisitting position.

OBJECTIVE: Midcervical flexion myelopathy is a rare but well-known complication of posterior fossa surgery. To reduce the risk, we routinely used somatosensory evoked potential (SSEP) monitoring during positioning of the patient. METHODS: Fifty-five consecutive patients were operated on for posterior fossa lesions in the semisitting position via a median (5 patients) or a lateral (50 patients) suboccipital approach. During positioning, monitoring of SSEPs by stimulation of the tibial nerve (T-SSEP) as well as by stimulation of the median nerve (M-SSEP) was established. In the case of pronounced SSEP changes, the head was repositioned. Surgery was started after SSEP recordings were unchanged as compared to the baseline investigation. RESULTS: Effective monitoring was possible in all cases. Whereas M-SSEP recordings showed no changes while placing patients in the sitting position, T-SSEP recordings were altered in 14 cases (25%). In cases using the midline approach, SSEP changes were never so pronounced to require repositioning of the head. Head flexion and rotation resulted in significant changes of T-SSEP recordings in eight patients (14.5%), requiring repositioning. In two cases, an amplitude loss was noted. In only two of these eight patients were M-SSEP recordings markedly changed. SSEP recordings after repositioning disclosed recovery of spinal cord function. In no patient were clinical signs of myelopathy observed postoperatively. CONCLUSION: We observed a high incidence of pronounced changes of T-SSEP recordings when the patient's head was flexed and rotated for lateral suboccipital craniotomy in the semisitting position. Despite the low specificity monitoring of T-SSEPs during positioning of the patient for posterior fossa surgery, the semisitting position is strongly recommended.

[Leukotriene synthesis after intracerebral hemorrhage: a further indicator for their pathophysiologic significance in the CNS]. / Leukotriensynthese nach intracerebralen Blutungen: Ein weiterer Indikator für ihre pathophysiologische Bedeutung im ZNS.

Blood brain cell contact activates lipid peroxidation and arachidonic acid metabolism as shown in animal experiments. Previous studies in tumor patients have shown that enhanced cysteinyl-leukotriene (cys-LT) formation leads to increasing perifocal edema. This suggests their involvement in CNS pathology. The purpose of this study is to measure the amounts of cys-LT released during blood-brain cell contact in patients with spontaneous intracerebral hemorrhage (ICH). Seventeen patients were divided into two groups. One of them was treated conservatively, the other group received a local rTPA therapy after stereotactic puncture and hematoma reduction by aspiration. Before treatment as well as during the following 5 days cerebral cys-LT release was measured analyzing the metabolites in patients urine. The mean cys-LT release before treatment ranged at 14.51 +/- 1.13 pg/mg creatinine/ml hematoma volume. In the conservative treatment group urinary cys-LT release dropped to 14.05 +/- 1.1 pg/mg creatinine/ml hematoma volume by the fifth day of treatment. The change of urinary cys-LT release in the operatively treated patients was much more distinct: Five days after rTPA therapy urinary cys-LT release was 11.23 +/- 0.6 pg/mg creatinine/ml tumor volume. The urinary cys-LT excretion at the end of the measurement was significantly lower in the operatively treated group (p < 0.05). In an additional experimental approach using dissociated rat brain cells plasmin was excluded as an activator for cerebral cys-LT formation. Variation in incubation time as well as the concentration of plasmin exhibited no difference in cys-LT release in comparison to the incubation of dissociated rat brain cells without any external stimulus. These results emphasize that rTPA does not influence cys-LT formation in a direct way. After experimental evidence, these results indicate now in a clinical evaluation that cerebral cys-LT formation is activated during blood-brain cell contact also in patients suffering from intracerebral hemorrhage. The amounts of cys-LT release depend on hematoma volume. Hematoma reduction by aspiration and rTPA treatment is followed by a distinct reduction of cys-LT release.

Intraoperative three-dimensional ultrasonography: an approach to register brain shift using multidimensional image processing.

Neuronavigation uses the skull as a reference system for transfer of image-space data to physical space during brain surgery. This requires a stable spatial relation between the skull and intracranial structures. However, especially dura opening and preparation for lesion removal causes brain shift. This shift may mislead the surgeon unless preoperatively defined image-space data are corrected for shifting online intraoperatively. Since a real-time modality is required intraoperatively, we propose three-dimensional (3 D) ultrasonography for detection of brain shift. By coupling common ultrasound probes (3.5/6.5 MHz) to a magnetic digitizer receiver 2 D-ultrasound scans were obtained intraoperatively along with their spatial orientation. 3 D-ultrasonography was achieved by alignment of sequentially obtained 2 D-scans. For multimodal matching, preoperative MRI data was segmented for landmarks (cerebral ventricles, lesion) automatically. The 3 D-ultrasonography data set scanned intraoperatively was contoured and matched with the MRI data set. Intraoperative 3 D-ultrasonography revealed excellent delineation of landmarks in almost real time in six patients studied. Matching of MRI data and intraoperative 3 D-ultrasonography data was successful with good correspondence of landmarks. Intraoperative 3 D-ultrasonography is proposed as a promising tool for on-line detection of brain shift during intracranial operations.

Time-dependent expression of donor- and host-specific major histocompatibility complex class I and II antigens in allogeneic dopamine-rich macro- and micrografts: comparison of two different grafting protocols.

Neural transplantation, as a therapeutic approach to Parkinson's disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-microliter macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3-6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.

Human MxA protein confers resistance to Semliki Forest virus and inhibits the amplification of a Semliki Forest virus-based replicon in the absence of viral structural proteins.

Mx proteins form a small family of interferon (IFN)-induced GTPases with potent antiviral activity against various negative-strand RNA viruses. To examine the antiviral spectrum of human MxA in homologous cells, we stably transfected HEp-2 cells with a plasmid directing the expression of MxA cDNA. HEp-2 cells are permissive for many viruses and are unable to express endogenous MxA in response to IFN. Experimental infection with various RNA and DNA viruses revealed that MxA-expressing HEp-2 cells were protected not only against influenza virus and vesicular stomatitis virus (VSV) but also against Semliki Forest virus (SFV), a togavirus with a single-stranded RNA genome of positive polarity. In MxA-transfected cells, viral yields were reduced up to 1,700-fold, and the degree of inhibition correlated well with the expression level of MxA. Furthermore, expression of MxA prevented the accumulation of 49S RNA and 26S RNA, indicating that SFV was inhibited early in its replication cycle. Very similar results were obtained with MxA-transfected cells of the human monocytic cell line U937. The results demonstrate that the antiviral spectrum of MxA is not restricted to negative-strand RNA viruses but also includes SFV, which contains an RNA genome of positive polarity. To test whether MxA protein exerts its inhibitory activity against SFV in the absence of viral structural proteins, we took advantage of a recombinant vector based on the SFV replicon. The vector contains only the coding sequence for the viral nonstructural proteins and the bacterial LacZ gene, which was cloned in place of the viral structural genes. Upon transfection of vector-derived recombinant RNA, expression of the beta-galactosidase reporter gene was strongly reduced in the presence of MxA. This finding indicates that viral components other than the structural proteins are the target of MxA action.

[Long-term socioeconomic outcome of lumbar disc microsurgery]. / Sozioökonomisches Langzeitergebnis nach lumbaler mikrochirurgischer Bandscheibenoperation.

Lumbar disc surgery is frequently performed but only few long-term outcome studies have been published. To assess the socioeconomic long-term outcome after lumbar disc surgery this study was performed using the Functional Economic Rating scale developed by Prolo et al. in 1986. The study group, mailed a questionnaire, consisted of 663 patients (18 to 60 years) operated on in 1983 or 1984. 23 patients (3.5%) died in the follow-up period. 406 (66% male and 34% female) patients answered the questionnaires (61%), therefore being eligible for further investigation. Mean age at the time of operation was 43 +/- 9.5 years. Preoperatively 29% of patients did sedentary work, 46% were employed in less strenuous and 25% in strenuous occupations. A motor deficit was present in 59% of patients preoperatively. In 51% the L4/5 level and in 38% the L5/S1 level was operated; 5% were operated in more than one level. In 45% an intraspinal sequester was found intraoperatively. Intra- and postoperative complications occurred in 14 patients (complication rate 3.4%). Six weeks after surgery all patients were examined in our outpatient department. 93% were more or less relieved of their complaints. 10 years after lumbar disc surgery a good outcome defined as Prolo scale 8-10 was achieved in 38%, a moderate outcome (Prolo scale 6-7) in 40% and a poor outcome (Prolo scale < 5) in 22%, respectively. Patients with strenuous occupations had a significantly (p < 0.001) less favorable outcome than patients with less strenuous or sedentary occupations. 32% were able to work in the previous profession with no restrictions. 42% were able to work part time at the previous occupation or with limited status and 9% had to change their profession. 17% were not able to gain any occupation postoperatively and retired. Vocational consequences depended on the preoperative type of occupation. 54% of patients with strenuous occupations had to change the profession or to retire compared to 15% of patients with sedentary occupations. During the 10-year follow-up period, 125 patients (31%) underwent at least another lumbar disc operation 4.8 +/- 3.8 years after their first surgery. Recurrence at the same level and the same side occurred in 14%. Reoperated patients had a significantly (p < 0.001) less favorable outcome than patients not operated on again. The results of this study indicate the recommendation of a prolonged postoperative course of treatment, especially in patients with strenuous occupations.

Improved graft survival and striatal reinnervation by microtransplantation of fetal nigral cell suspensions in the rat Parkinson model.

A microtransplantation approach has been used in order to achieve more complete reinnervation of the dopamine denervated rat striatum by fetal nigral cell suspensions injected into multiple striatal sites. A total of 450,000 cells, obtained from the ventral mesencephalon of embryonic day 14 rat fetuses, were implanted either in the conventional way as two 1.8-microliters deposits centrally in the head of the caudate-putamen ('Macro grafts'), or as eighteen 0.2-microliter deposits disseminated over six needle penetrations in the same area using a 50-70 microns glass capillary tip ('Micro grafts'). Non-grafted lesioned rats served as controls. Dopamine neuron survival (as assessed by tyrosine hydroxylase immunohistochemistry at 4 months after transplantation) was 2.8-fold greater in the Micro grafts as compared to the Macro grafts. Striatal dopamine tissue levels (determined in a separate group of rats) was increased 2.5-fold in the head of the caudate-putamen (from 12.5% of normal in the Macro graft group to 30% of normal in the Micro graft group). Consistent with this, the overall graft-derived tyrosine hydroxylase positive fiber outgrowth was more extensive in the Micro graft group and covered larger areas of the previously denervated caudate-putamen. The results show that distribution of the fetal nigral tissue in multiple small deposits provides for increased dopamine neuron survival, probably because of a closer contact between the implanted cells and the surrounding host striatal tissue in the small-sized graft deposits. Less bleeding and necrosis at the implantation site may also have contributed to this effect. The present microtransplantation procedure is an efficient means to increase overall dopamine neuron survival and to achieve more complete reinnervation of the denervated striatum in the rat Parkinson model. It also substantially increased the reproducibility of DA graft survival between animals.

Restoration of complex sensorimotor behavior and skilled forelimb use by a modified nigral cell suspension transplantation approach in the rat Parkinson model.

While intrastriatal transplants of dopamine-rich ventral mesencephalic tissue are effective in reversing a variety of drug-induced behaviors in the rat Parkinson model, previous studies have failed to obtain significant graft-induced effects on deficits in certain aspects of complex sensorimotor behaviors. In the present study we have applied a modified cell suspension transplantation procedure, which allows more reproducible and consistent ventral mesencephalic transplants of large size, as well as more wide-spread distribution of the ventral mesencephalic tissue over multiple graft sites within the denervated caudate-putamen. Using this approach it has for the first time been possible to obtain significant amelioration of the lesion-induced deficits in skilled forelimb use and in the rats ability to switch from one behavior (eating) to another (orientation towards tactile stimuli), so-called disengage behavior. Rats with unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine pathway received a total of 450,000 fetal ventral mesencephalic cells, implanted either as two large deposits along a single injection tract ("Macro" grafts), or as 18 small deposits along six injection tracts in the head of the denervated caudate-putamen ("Micro" grafts) and the behavioral changes were studied up to three months after transplantation. On the drug-induced tests, both types of transplants reversed amphetamine- and D1-receptor agonist-induced turning, and produced a partial (50-75%) reduction in apomorphine-induced and D2-receptor agonist-induced turning. On the spontaneous sensorimotor tests, both types of grafts reversed the deficit in simple sensorimotor orientation. In addition, the Micro-grafted animals (which produced the most extensive reinnervation of the denervated striatum) showed a significant improvement in skilled forelimb use and in response latency in the disengage behavior test. Although the large sized Macro-grafted animals showed a similar trend, it did not reach significance. Moreover, the Micro grafts had a more pronounced effect on spontaneous turning behavior in a conditioned response test. The improvement in response latency in the disengage test was significantly correlated with the dopamine level in the nucleus accumbens, whereas the magnitude of the conditioned turning response was significantly correlated with the dopamine levels in the head of the caudate-putamen. The results show that intrastriatal nigral transplants, despite their ectopic placement, can ameliorate lesion-induced deficits also in more complex sensorimotor behaviors. This improved graft effect is likely to depend on both extensive dopaminergic reinnervation throughout the head of the caudate-putamen, as well as on closer integration of the grafted nigral tissue with the host striatal circuitry.

MxA-dependent inhibition of measles virus glycoprotein synthesis in a stably transfected human monocytic cell line.

The alpha/beta (type I) interferon-inducible human MxA protein confers resistance to vesicular stomatitis virus (VSV) and influenza A virus in MxA-transfected mouse 3T3 cells (3T3/MxA). We investigated the inhibitory effects of the MxA protein on measles virus (MV) and VSV in the human monocytic cell line U937. In transfected U937 clones which constitutively express MxA (U937/MxA), the release of infectious MV and VSV was reduced approximately 100-fold in comparison with control titers. Transcription of VSV was inhibited similar to that observed for 3T3/MxA cells, whereas no difference was detected for MV in the rates of transcription or the levels of MV-specific mRNAs. In contrast, analysis of MV protein expression by immunofluorescence and immunoprecipitation revealed a significant reduction in the synthesis of MV glycoproteins F and H in U937/MxA cells. These data demonstrate a virus-specific effect of MxA which may, in the case of MV, contribute to the establishment of a persistent infection in human monocytic cells.