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Displaced intra-articular fractures of the tarsal navicular.

Between 1980 and 1987, twenty-one patients who had a displaced fracture of the body of the tarsal navicular were treated with open reduction and internal fixation. A classification system was devised on the basis of the direction of the fracture line, the pattern of disruption of the surrounding joints, and the direction of displacement of the foot. In a Type-1 injury, the fracture line is in the coronal plane and there is no angulation of the fore part of the foot. In a Type-2 fracture, the primary fracture line is dorsal-lateral to plantar-medial, and the major fragment and the fore part of the foot are displaced medially. In a Type-3 injury, there is a comminuted fracture in the sagittal plane of the body of the tarsal navicular, and the fore part of the foot is laterally displaced. Satisfactory reduction, which was defined as restoration of more than 60 per cent of the joint surface in the anteroposterior and lateral planes, was achieved in all Type-1 injuries, 67 per cent of the Type-2 fractures, and 50 per cent of the Type-3 fractures. Radiographic evidence of healing was seen at an average of 8.5 weeks after injury. At an average follow-up of forty-four months (range, twelve to 106 months), a good result was noted in fourteen patients (67 per cent); a fair result, in four (19 per cent); and a poor result, in three (14 per cent). Both the type of fracture and the accuracy of the operative reduction directly correlated with the final clinical outcome.

Adolescent↗

[Effect of acute and chronic deprivation of catecholaminergic system activity induced by 6-hydroxydopamine on the behavior of the rat].

On 202 male rats of Wistar line, a study was carried out of the effect of chronic and acute deprivations of the brain CA-systems activity resulting from administration of 6-OHDA on investigating behaviour and learning. Chronic deprivation of CA-systems activity by neonatal administration of 6-OHDA (100 mg/kg subcutaneously) and their acute deprivation by intracerebral administration of 6-OHDA to adult rats (150 mkg in each lateral ventriculus) was accompanied by similar deep changes of behaviour. Both forms of deprivation reduced the investigating activity of the animals in the open field. In both cases, the above 6-OHDA dozes sharply impeded the learning of animals with emotionally negative reinforcement, with no significant influence on learning with emotionally positive reinforcement. Both forms of deprivation of CA-systems activity weakened the reaction of frustration elicited by a sharp reduction of food reinforcement.

Animals↗

Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells.

Nestin is a recently described member of the intermediate filament (IF) protein family that is especially abundant in neuroepithelial stem cells of the rat. The studies described here examine this class VI IF protein in the normal human developing central nervous system (CNS), human brain tumor-derived cell lines, and tissue samples of human CNS tumors. Human nestin exhibited biochemical and immunochemical properties similar to those of rat nestin. Further, as in the rat, nestin was detected immunohistochemically in several different types of immature human CNS cells, i.e. germinal matrix cells, neuroepithelial cells lining the central canal, radial glia and vascular cells. Nestin appeared in these cells at the earliest gestational age (i.e., 6 weeks) examined here and then it declined in all but the vascular cells at later embryonic stages. Nestin also was detected by immunocytochemistry in 6 of 7 primitive neuroectodermal tumor cell lines and in both of 2 malignant glioma cell lines examined. In these cell lines, nestin co-localized incompletely with bundles of IFs containing other IF proteins (i.e., vimentin, glial filament, neurofilament). Nestin was ubiquitous in a wide variety of brain tumors, but was most prominent in gliomas. The transient expression of nestin in primitive neuroepithelial cells at early stages of human embryogenesis and its abundance in neuroepithelial tumors suggest a role for nestin IFs in cellular events that precede the exit of embryonic CNS stem cells from the cell cycle and the commitment of the progeny of these stem cells to a specific lineage. The subsequent induction of different members of the IF protein family in phenotypically distinct CNS cells (i.e. neurons, glia) and the elimination of nestin from almost all differentiated CNS cells, imply that different classes of IFs subserve functions that are closely linked to the maturational state, as well as the lineage, of CNS cells.

Adolescent↗

Treatment of AIDS-related primary central nervous system lymphoma with zidovudine, ganciclovir, and interleukin 2.

AIDS-related primary central nervous system lymphoma (AIDS PCNSL) is a rapidly fatal disease. Conventional therapeutic modalities offer little and new approaches are needed. Previous work has shown that zidovudine (AZT) in combination with other agents is active in retroviral lymphomas. Epstein-Barr virus (EBV) is detected in tumor tissue and cerebrospinal fluid of AIDS PCNSL patients. In a preliminary in vitro study we found that an Epstein-Barr virus-positive B cell line underwent apoptosis on coculture with AZT. This effect was accentuated by the addition of ganciclovir (GCV). We treated five patients with AIDS PCNSL with a regimen consisting of parenteral zidovudine (1.6 g twice daily), ganciclovir (5 mg/kg twice daily), and interleukin 2 (2 million units twice daily). Four of five had an excellent response. Two patients are alive and free of disease 22 and 13 months later; another responded on two separate occasions, 5 months apart, and the last patient responded with a 70-80% regression of tumor but could not be maintained on therapy owing to myelosuppression. We conclude that parenteral zidovudine, ganciclovir, and interleukin 2 is an active combination for AIDS-related central nervous system lymphoma.

Adolescent↗

Antitumor efficacy of interleukin-2 alone and in combination with adriamycin and dacarbazine in murine solid tumor systems.

Recombinant interleukin-2 (IL-2)/chemotherapy combinations have recently entered clinical trial. The rationale for sequencing has primarily been empiric or based on in vitro data. To establish in vivo models for chemoimmunotherapy trials, we investigated IL-2 alone and in combination with dacarbazine (DTIC) and adriamycin. IL-2 (as a single agent given i.v. at 1-3 x 10(5) Cetus units once daily for 5 days, repeated 7-10 days later), was highly active against an immunogenic line of colon adenocarcinoma no. 11/A [tumor growth inhibition (T/C) = 0% with cures]. It was modestly active against colon adenocarcinoma no. 38 (T/C = 39%), mammary adenocarcinoma no. 16/C (T/C = 18%), and B16 melanoma (T/C = 21%). IL-2 was inactive against colon adenocarcinoma no. 7/A (T/C = 83%). Combination trials were done using DTIC and IL-2 against colon no. 7/A and upstaged colon no. 11/A. The combination of adriamycin and IL-2 was tested against mammary adenocarcinoma no. 16/C. In the DTIC/IL-2 combination trials, the combination was superior over either agent used alone. In the IL-2/adriamycin trials, the combination was no better than adriamycin alone at optimum dosages.

Adenocarcinoma↗

Morphology and histology of the male reproductive system in two species of internally inseminating South American catfishes, Trachelyopterus lucenai and T. galeatus (Teleostei: Auchenipteridae).

As part of an effort to characterize reproductive modifications in internally inseminating catfishes, ovaries and male reproductive systems were examined histologically in two species of auchenipterid catfishes, Trachelyopterus lucenai and T. galeatus, from southeastern Brazil. Internal insemination was documented in both species by the presence of sperm within ovaries. Although there is some variation in gross morphology of the male reproductive systems between the two species, both have four main regions: spermatogenic lobes, sperm storage regions, and secretory and storage regions of the seminal vesicle. In both species, the anterior portion of the reproductive system is spermatogenic and divided into numerous finger-like lobes. Posterior to the spermatogenic area is the storage region of the seminal vesicle, a large median structure with a honeycomb-like appearance. This region is consistently larger in T. lucenai. Attached to the storage region of the seminal vesicle in both species are secretory lobes comprised of tubules lined by secretory cells. These lobes in T. lucenai are small and located on the anterior aspect of the storage region of the seminal vesicle, whereas in T. galeatus the lobes are much larger and located laterally. The sperm storage regions of T. lucenai consist of two large lobes located ventral to the storage region of the seminal vesicle. Highly compact sperm packets (spermatozeugmata) fill the lumina of the ramifying tubules of these regions. Each spermatozeugma consists of elongate nuclei tightly arranged parallel to one another. In T. galeatus two distinct sperm storage regions are present. Just posterior to the spermatogenic lobes a series of small lobes serve as anterior sperm storage regions. Posterior to the secretory lobes of the seminal vesicle is a series of lobes, at the most posterior aspect of the reproductive tract, that serve as posterior sperm storage regions. Both are identical, histologically, to the sperm storage regions of T. lucenai. An absence of compact spermatozeugmata in the T. galeatus specimens may be related to variations in their sexual activity. The descriptions presented here allow for consistent terminology for comparison of regions of the male reproductive system based on presumed function.

Animals↗

Transition from self tilt to object tilt during maintained lateral tilt in parabolic flight.

19 young healthy subjects were subjected to parabolic rollercoaster flight. A horizontal luminous line was seen by the subjects in a headfixed goggle device. During the hypergravic phases of parabolic flight the luminous line seemed to rotate into and during the hypogravic phase against the direction of static head tilt. Ocular counter rotation and activity of the neck position receptors cannot explain these subjective rotations. We conclude that information from the otolith system, converging with visual information within the brain, dislocated the headfixed visual target line. While the retinal image of the luminous line remains unchanged, loading and unloading the otoliths in parabolic flight changes the sensation of self tilt into object tilt, hereby subjectively rotating visual targets such as the luminous line.

Eye Movements↗

Near and far visual space in unilateral neglect.

A 24-year-old right-handed woman with a right temporal hematoma showed marked left visual neglect for far but not near space in a variety of tasks systematically given in near and far distance conditions. This case thus provides the dissociation opposite to Halligan and Marshall's patient, who had neglect for near but not far space after a right parietal stroke. Furthermore, although she made rightward errors in bisecting far-distant lines, our patient made smaller opposite leftward errors for near-distant lines. The evidence that unilateral neglect of far and near visual space may exist independently supports a division in the neural systems subserving attention to different compartments of the extrapersonal space in humans.

Adult↗

GABA-immunoreactive terminals synapse on primate spinothalamic tract cells.

Gamma-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the vertebrate nervous system. Several lines of evidence suggest that GABA plays an important role in the processing and modulation of sensory input in the spinal cord dorsal horn. In the present study, the relationship between GABA-immunoreactive (GABA-IR) terminals and spinothalamic tract (STT) cells in the monkey lumbar cord was investigated. Physiologically characterized STT cells, one located in lamina V and two located in lateral lamina IV, were intracellularly injected with horseradish peroxidase (HRP). A fourth STT cell, located in lamina I, was retrogradely labeled following injection of HRP into the contralateral thalamus. Immunogold labeling of ultrathin sections through the cell bodies and proximal dendrites of the STT neurons demonstrated that the percentage of the GABA-IR terminals in contact with these profiles was 24.7% and 36%, respectively. The average STT surface length contacted by GABA-IR terminals for cell bodies and proximal dendrites was 18.2% and 26.7%, respectively. For the lamina I cell, 7 out of 35 (20%) of the terminals were GABA-IR and they covered 9.6% of the surface analyzed. These data demonstrate that GABA-IR terminals synapse directly on STT cells, constituting a substantial proportion of the terminal population on these cells. Furthermore, compared to the cell bodies, a greater percentage of the input on the proximal dendrites is GABAergic. These anatomical data are consistent with the findings of a previously published iontophoretic study that demonstrated that GABA can exert a strong inhibitory influence on STT cells. These findings are discussed in relation to GABAergic involvement in tonic and phasic inhibition of STT neurons.

Animals↗

A Cre recombinase transgene with mosaic, widespread tamoxifen-inducible action.

Cre-mediated site-specific recombination allows conditional transgene expression or gene knockouts in mice. Inducible Cre recombination systems have been developed to bypass initial embryonic lethal phenotypes and provide access to later embryonic or adult phenotypes. We have produced Cre transgenic mice in which excision is tamoxifen inducible and occurs in a widespread mosaic pattern. We utilized our Cre excision reporter system combined with an embryonic stem (ES) cell screen to identify ES cell clones with undetectable background Cre activity in the absence of tamoxifen but efficient excision upon addition of tamoxifen. The CreER transgenic mouse lines derived from the ES cells were tested using the Z/AP and Z/EG Cre reporter lines. Reporter gene expression indicated Cre excision was maximal in midgestation embryos by 2 days after tamoxifen administration, with an overall efficiency of 5-10% of cells with Cre excision. At 3 days after tamoxifen treatment most reporter gene expression marked groups of cells, suggesting an expansion of cells with Cre excision, and the proportion of cells with Cre excision was maintained. In adults, Cre excision was also observed with varying efficiencies in all tissues after tamoxifen treatment.

Animals↗

Implantation of polymer-encapsulated human nerve growth factor-secreting fibroblasts attenuates the behavioral and neuropathological consequences of quinolinic acid injections into rodent striatum.

Delivery of neurotrophic molecules to the central nervous system has gained considerable attention as a potential strategy for the treatment of neurological disorders. In the present study, a DHFR-based expression vector containing the human nerve growth factor gene (hNGF) was transfected into a baby hamster fibroblast cell line (BHK). Using an immunoisolatory polymeric device, encapsulated BHK-control cells and those secreting hNGF (BHK-hNGF) were transplanted unilaterally into rat lateral ventricles. Three days later, the same animals received unilateral injections of quinolinic acid (QA, 225 nmol) or the saline vehicle into the ipsilateral striatum. Approximately 2 weeks following surgery, animals were tested for apomorphine-induced rotation behavior. Animals which received BHK-hNGF cells rotated significantly less than those animals receiving BHK-control cells or QA alone. Histological analysis 29-30 days following capsule implantation demonstrated that BHK-hNGF cells attenuated the extent of host neural damage produced by QA as assessed by a sparing of ChAT- and NADPH-d-positive neurons. Moreover, a lessened GFAP reaction was apparent within the striatum of animals receiving BHK-hNGF cells. As measured by ELISA, hNGF was released by the encapsulated BHK-hNGF cells prior to implantation and following removal. Morphology of retrieved capsules revealed numerous viable and mitotically active BHK cells. These results suggest that implantation of polymer-encapsulated hNGF-releasing cells can be used to protect neurons from excitotoxin damage.

Animals↗

Pathogenesis of experimental rabies in mice: an immunohistochemical study.

The spread of rabies virus in the central nervous system of mice was examined after hindlimb footpad and intracerebral inoculation of the CVS strain of fixed rabies virus. All mice developed paralytic rabies. After intracerebral inoculation there was early simultaneous infection of neurons in the cerebral cortex and pyramidal neurons of the hippocampus, and later there was spread to the cerebellum. After high-dose intracerebral inoculation there was early infection in ependymal cells lining the lateral ventricles and neurons adjacent to the central canal of the spinal cord, suggesting that rabies virus entry into the CNS occurs, at least in part, by a cerebrospinal fluid pathway. The sequence of involvement was different after hindlimb footpad inoculation. Infection became established in the cerebellum on day 5, in the cerebral cortex on day 6, and in the hippocampus on day 8. CA3 was initially affected, CA1 became infected 2 days later, and there was much less involvement of the dentate gyrus. Hippocampal infection occurred late relative to the rest of the brain after peripheral inoculation, but not after intracerebral inoculation. The hippocampus is not a good location for the detection of early brain infection after peripheral inoculation, although it may be involved when a natural rabies vector has the ability to transmit infection. These findings also raise questions about the mechanisms for the limbic dysfunction observed in clinical rabies.

Animals↗

Ion-channel activities regulate transmembrane signaling in thymocyte apoptosis and T-cell activation.

Several examples have shown that plasma membrane ion channels (e.g., Ca2+ and K+ channels) make an important contribution to lymphocyte activation or thymocyte apoptosis. Here we report on the importance of these ion channels in the sensitivity or resistance of lymphoid cells to extracellular ATP-induced apoptosis. Thymocytes of Balb/c mice responded to extracellular ATP (ATPex) sensitively, with an immediate increase in the intracellular calcium level and later with an increased membrane permeability to low MW markers. Mature (medullary) thymocytes showed a higher sensitivity than did cortical thymocytes. Three human lymphoma cell lines, including SUPT13, a cell line reported to be sensitive to TcR/CD3 activation-induced apoptosis, showed a high resistance to ATPex action. These observations suggest that maturation/differentiation state-dependent activity or disappearance of early ATP-receptor operated signaling systems (including ion channels) are critical for the cells in developing towards apoptosis. Using the patch-clamp technique we demonstrated that bretylium tosylate (a particular K(+)-channel blocker) known as inhibitor of T-lymphocyte proliferation also influences the single-channel properties of voltage-gated K+ channels through depressing whole-cell K+ currents. This finding is yet another example underlying the importance of K+ channel activity in T-lymphocyte proliferation.

Adenosine Triphosphate↗

In vivo dynamics and distribution of intracerebroventricularly administered gadodiamide, visualized by magnetic resonance imaging.

Direct injections into the cerebroventricles have been extensively utilized in neurophysiological studies. Mapping the distribution of injectate after intracerebroventricular injection has been made only by post mortem analysis, and the dynamic distribution of injectate within the brain has not been well characterized. In this report, we apply contrast-enhanced magnetic resonance imaging to study the pharmacokinetics and extent of non-ionic gadodiamide transport into brain tissue in vivo after intracerebroventricular administration. The results indicate that intracerebroventricular injectate travels quickly throughout the ventricular system from the lateral ventricular site of injection to the fourth ventricle and foramina of Luschka and Magendie within 2 min. After this, the signal intensity begins to increase in the periventricular and paraventricular brain parenchyma. Contrast enhancement is visible 2 mm into the brain tissue from the ventricles. Quantitative analysis of the data shows that the transport of gadodiamide across the ependymal layer that lines the cerebrospinal fluid space characterized a rate constant of 0.066+/-0.017 min(-1). These results provide a better understanding of chemical transport and diffusion following direct injection into the cerebroventricles. They provide information on the in vivo dynamics of injectate after intracerebroventricular administration, and show that contrast enhanced magnetic resonance imaging may be used to more precisely define the target sites of chemicals after intracerebroventricular administration into the brain.

Animals↗

SCL/tal-1-dependent process determines a competence to select the definitive hematopoietic lineage prior to endothelial differentiation.

Hematopoiesis in most vertebrate species occurs in two distinct phases, primitive and definitive, which diverge from FLK1(+)VE-cadherin(-) mesoderm and FLK1(+)VE-cadherin(+) endothelial cells (EC), respectively. This study aimed at determining the stage at which hematopoietic lineage fate is determined by manipulating the SCL/tal-1 expression that is known to be essential for the early development of the primitive and definitive hematopoietic systems. We established SCL-null ES cell lines in which SCL expression is rescued by tamoxifen-inducible Cre recombinase-loxP site-mediated recombination. While no hematopoietic cells (HPC) were detected in SCL-null ES cell differentiation cultures, SCL gene reactivation from day 2 to day 4 after initiation of differentiation could rescue both primitive and definitive hematopoiesis. SCL reactivation at later phases was ineffective. Moreover, generation of VE-cadherin(+) EC that can give rise to definitive HPC required SCL reactivation prior to VE-cadherin expression. These results indicated that the competence to become HPC is acquired at the mesodermal stage by a SCL-dependent process that takes place independently of determination of endothelial fate.

Animals↗

An on-line look at automatic contrast and correction of behavior categorizations and dispositional inferences.

The current study examined on-line behavior recategorization as a mechanism underlying corrections for contextual influences in dispositional inferences. After watching an initial comparison video that portrayed either a successful or unsuccessful performance on a spatial ability task, cognitive load and no load participants watched and made real-time ratings of a target performance. The comparison video was expected to exert a contrastive influence on participants' automatic impressions of the performance (behavior categorizations) and the child's intelligence (dispositional inferences). Load participants' on-line and post-video performance and ability ratings showed this expected effect, as did no load participants' initial on-line performance ratings. However, no load participants' later on-line and post-video ratings did not. These findings support the notion that corrections for contextual influence can occur at the level of behavior identification as perceivers encode behavioral cues.

Analysis of Variance↗

Angle-independent motion measurement by correlation of ultrasound signals assessed with a single circular-shaped transducer.

In medicine, pulsed ultrasound is a widespread noninvasive technique that measures motion in the direction of the ultrasound beam, i.e., axial motion. The magnitude of the actual motion can be determined only if the angle between the ultrasound beam and the direction of motion (transducer-to-motion angle) is known. For blood flow measurements, current pulsed ultrasound systems assume this angle to be equal to the angle between the ultrasound beam and the longitudinal direction of the vessel, as can be estimated from a two-dimensional brightness-mode (B-mode) image that is obtained prior to the blood flow measurement. For tissue motion measurements, current pulsed ultrasound systems are mostly unable to determine the transducer-to-motion angle. Recently, a model has been derived for the correlation of(analytic) radiofrequency (rf) signals, assessed with a circular-shaped ultrasound transducer along the same line of observation. In the present paper, this model is used to derive estimators, requiring only the calculation of a few correlation coefficients, for the motion components (axial, lateral and actual) and for some of the signal parameters (center frequency, bandwidth and signal-to-noise ratio) of the assessed rf signals. The transducer-to-motion angle can be derived from the estimated motion components. For the evaluation of the estimators, rf signals were acquired with a motion-controlled experimental arrangement. The results of the evaluation study show that the transducer-to-motion angle can be estimated with a mean standard deviation of less than 2 degrees.

Algorithms↗

[Interhemisphere neurochemical differences in the brain of silver foxes selected for behavior and the problem of directed asymmetry].

The study deals with the mechanisms that bring about a directional asymmetry in the expression of some morphological traits observed in some animals subjected to experimental domestication. The key role in the integration of development is attributed to the genetic systems controlling the activity of brain neurotransmitter systems. Therefore, the investigation of directional asymmetry of morphological traits began with the analysis of interhemispheral differences in neurotransmitter activity in animal lines selected for domestic and aggressive behavior. Experiments on silver foxes reveal interhemispheral differences in the dopaminergic system emerging in the striatum. An increased dopamine level is observed in the right half of the striatum of aggressive foxes and in both right and left halves of the striata of domestic foxes. On the basis of the literature data, it is suggested that the considerable increase in the dopamine level in the right halves of the striata of both aggressive and domestic animals is related to a genetic increase in the manifestation of emotional response in both lines, whereas its increase in the left half of the striatum of domesticated foxes may be related to a correlated deterioration of the function of the pituitary-adrenal system.

Animals↗