Changes of synovial fluid biomarker levels after opening wedge high tibial osteotomy in patients with knee osteoarthritis.

OBJECTIVE: The purpose of this study was to evaluate the effects of high tibial osteotomy (HTO) on the biological status of knee osteoarthritis (OA) using joint markers in synovial fluid (SF). METHODS: Fifty patients with medial compartmental OA of the knee who underwent opening wedge HTO were enrolled. Paired SF samples from the affected knee and arthroscopic evaluation of articular cartilage were collected at the time of HTO surgery and the time of plate removal (postoperative 17 ± 4 months). The concentrations of the following SF biomarkers were measured: interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumour necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, MMP-13, vascular endothelial growth factor (VEGF), and cartilage oligomeric matrix protein (COMP). The Knee Society Score (KSS) and hip-knee-ankle (HKA) angle were assessed before and 2 years after HTO. RESULTS: The KSS knee and function scores were significantly improved after HTO (mean changes of 36.4 and 23.7, respectively). The mean HKA angle was altered from mechanical varus (-8.6°) to valgus (5.2°). Concentrations of IL-6, IL-8, MMP-2, MMP-3, MMP-13, VEGF, and COMP in SF were significantly decreased after HTO (mean changes of -49.1%, -30.2%, -31.1%, -26.3%, -30.8%, -42.5%, and -13.7% from preoperative baseline, respectively). The cartilage status was improved in 19 cases (38%) after HTO. However, changes of all biomarkers were not significantly different between subjects with and without an improved cartilage status. CONCLUSIONS: SF levels of biochemical markers for cartilage degradation and synovial inflammation were altered after HTO, suggesting an improvement in the OA disease state.

Neural correlates of a nonjammable electrolocation system.

The detection of objects by the electrosensory system of weakly electric fish is subject to electrical interference such as that produced by the electric organ discharges emitted by neighboring electric fish. Most electric fish species have a behavioral reflex, the jamming avoidance response, which protects their electrolocation system against jamming. Sternopygus is unique in that it has no jamming avoidance response, yet can electrolocate even in the presence of jamming. It appears that Sternopygus protects electrolocation not by a behavioral strategy but by first-order central processing mechanisms that can distinguish between localized changes in the amplitudes of electric organ discharges caused by objects and large-field amplitude modulations caused by jamming. This mechanism acts as a local contrast detector and is functionally similar to the one used by retinal cells to respond to local contrast in light but not to overall changes in illumination.

Chemosensitivity of patients with recurrent esophageal cancer receiving perioperative chemotherapy.

Perioperative chemotherapy (CT) and chemoradiotherapy are widely used for advanced esophageal cancer. We evaluated the chemosensitivity of patients displaying recurrent esophageal cancer after esophagectomy with perioperative CT. From the database at National Cancer Center Hospital in Tokyo, we extracted recurrent esophageal cancer cases after perioperative CT and evaluated the effectiveness of the first CT against the recurrent disease according to the duration between termination of the original perioperative CT and recurrence with treatment-free intervals (TFIs) 6 months. Systemic CT for their recurrent disease was performed for 30 esophageal cancer patients after perioperative CT. All patients received 5-fluorouracil and cisplatin as perioperative CT, with relapses occurring at TFIs 6 months in 19 patients (all received platinum-containing regimens). The response rate of patients experiencing a recurrence at TFIs 6 months was 0 and 37% (P = 0.029), the median progression-free survival was 2.8 and 4.8 months (log-rank P = 0.001) and the median overall survival was 6.1 and 10.2 months (log-rank P = 0.012), respectively. Recurrence at the TFI

Metabolic cost of lateral stabilization during walking in people with incomplete spinal cord injury.

People with incomplete spinal cord injury (iSCI) expend considerable energy to walk, which can lead to rapid fatigue and limit community ambulation. Selecting locomotor patterns that enhance lateral stability may contribute to this population's elevated cost of transport. The goal of the current study was to quantify the metabolic energy demands of maintaining lateral stability during gait in people with iSCI. To quantify this metabolic cost, we observed ten individuals with iSCI walking with and without external lateral stabilization. We hypothesized that with external lateral stabilization, people with iSCI would adapt their gait by decreasing step width, which would correspond with a substantial decrease in cost of transport. Our findings support this hypothesis. Subjects significantly (p<0.05) decreased step width by 22%, step width variability by 18%, and minimum lateral margin of stability by 25% when they walked with external lateral stabilization compared to unassisted walking. Metabolic cost of transport also decreased significantly (p<0.05) by 10% with external lateral stabilization. These findings suggest that this population is capable of adapting their gait to meet changing demands placed on balance. The percent reduction in cost of transport when walking with external lateral stabilization was strongly correlated with functional impairment level as assessed by subjects' scores on the Berg Balance Scale (r=0.778) and lower extremity motor score (r=0.728). These relationships suggest that as functional balance and strength decrease, the amount of metabolic energy used to maintain lateral stability during gait will increase.

Tangential organization of callosal connectivity in the cat's visual cortex.

Cells and/or terminals of corticocortical pathways in mammalian visual cortex often have a discontinuous distribution across the surface of the cortex. A modular organization of cortical function has been shown to underlie the tangential segregation of many inputs and outputs. Here, we present evidence that the callosal pathway in the visual cortex of the cat follows these general principles. Large injections of wheat germ agglutinin-horseradish peroxidase or biotinylated dextran amine were made in areas 17 and 18, and callosal labeling was analyzed in tangential sections. The band of callosal cells and terminals straddling the border of areas 17 and 18 was not uniform but varied in density in a complicated fashion. Fluctuations in density of callosal connections became more clear 2-3 mm lateral or medial to the 17/18 border, as the callosal labeling became less dense. Here, regular fluctuations with a periodicity of about 1 mm in area 17, and slightly greater than 1 mm in area 18 were apparent. Cytochrome oxidase staining in areas 17 and 18 showed a pattern of dense blobs with the same spacing as the callosal labeling in these areas, and the blobs were found to align with the patches of callosal labeling. Larger, more irregularly spaced stripes of callosal labeling extended from the lateral part of area 18 across area 19 and into more lateral visual areas. These results suggest that the callosal pathway in the cat's visual cortex has a patchy distribution similar to many ipsilateral corticocortical projections, and that the columnar system marked by cytochrome oxidase is important for the organization of (interhemispheric) corticocortical connectivity in cats.

Intracortical connections and their physiological correlates in the primary auditory cortex (AI) of the cat.

We studied the functional and anatomical properties of the intrinsic connections in the primary auditory cortex (AI) of the cat by using physiological mapping and retrograde tracing methods. Our results revealed that a focal microinjection of tracer labeled as many as five intracortical patches in AI. The patches contained labeled pyramidal and non-pyramidal cell types, most of which were clustered in the middle layers. A densely distributed anterograde-like reaction product was present in the superficial layers above the labeled cells. The distribution of the patches was anisotropic, with most patches occurring dorsal, ventral, and anterior to the injection site. We examined the correlation between the characteristic frequency (CF) and binaural response properties of the injected and labeled regions. We found local labeling in regions possessing CFs equivalent to or slightly greater than that of the injected area. This appears to be a specific connection since we were able to predict the general location of many of the patches on the basis of the organization of the isofrequency domains. Patches were more numerous dorsoposterior to the injection site when the isofrequency contours ran obliquely (i.e., dorsoposterior to ventroanterior) across AI. The binaural response properties of the injected and labelled regions, however, were unrelated.

Light and electron microscopical studies on the spherical neurons in the electrosensory lateral line lobe of the gymnotiform fish, Sternopygus.

Spherical cells are a principal cell type of the electrosensory lateral line lobe (ELLL) and play a crucial role in the jamming avoidance response (JAR) behavior. Since Sternopygus, a low frequency gymnotiform genus, does not display a JAR we searched for spherical cells in its ELLL. While present in Sternopygus, spherical cells differed remarkedly from those in the high-frequency gymnotiforms, Eigenmannia and Apteronotus. This study reveals species-characteristic differences in the morphology and synaptology of the spherical cell, a projection neuron located in the deep neuropil layer (DNL) of the ELLL. In contrast to the adendritic spherical cell of other species, the spherical neuron in Sternopygus exhibits an extensive basilar dendrite that extends into the primary electroreceptive afferent zone, the deep fiber layer (DFL). In Sternopygus, these neurons are distributed evenly across the full length of each tuberous subdivision, with cell densities highest in the centrolateral subdivision. At the ultrastructural level, the contacts on the soma, proximal, and distal dendrite of the spherical neuron in Sternopygus are asymmetrical chemical synapses, quite distinct from the electrotonic gap junctions found on the spherical neurons of other species.

Laminar and columnar patterns of geniculocortical projections in the cat: relationship to cytochrome oxidase.

We examined the laminar and columnar arrangement of projections from different layers of the lateral geniculate nucleus (LGN) to the visual cortex in the cat. In light of recent reports that cytochrome oxidase blobs (which in primates receive specific geniculate inputs) are also found in the visual cortex of cats, the relationship between cytochrome oxidase staining and geniculate inputs in this species was studied. Injections of wheat germ agglutinin-conjugated horseradish peroxidase were made into the anterior "genu" of the LGN, where isoelevation contours of the geniculate layers are distorted due to the curvature of the nucleus. Consequently, anterograde labeling from the various LGN layers was topographically separated across the surface of the cortex, and labeling in a particular isoelevation representation of the cortex could be associated with a specific layer of the LGN. Labeling from the A layers, which contain X and Y cells, was coextensive with layers 4 and 6 in both area 17 and area 18, as previously reported. Labeling from the C layers, which contain Y and W cells, occupied a zone extending from the 4a/4b border to part way into layer 3 in area 17. The labeling extended throughout layer 4 in area 18. There was also labeling in layer 5a and layer 1 in both area 17 and area 18. Except in layer 1, labeling from the C layers was patchy. In the tangential plane, adjacent sections stained for cytochrome oxidase showed that the patches of labeling from the C laminae aligned with the cytochrome oxidase blobs. The cytochrome blobs were visible in layers 3 and 4a, but not in layer 4b in both areas 17 and 18. These results suggest that W cells project specifically to the layer 3 portion of the blobs, while Y cells, at least those of the C layers, project specifically to the layer 4a portion of the blobs in area 17. The heavy synaptic drive of the Y cells is probably the cause of the elevated metabolism, and thus, higher cytochrome oxidase activity, of the blobs.

Comparative morphology of three types of projection-identified pyramidal neurons in the superficial layers of cat visual cortex.

The morphology and dendritic organization of corticocortical neurons in the superficial layers of area 18 that project to area 17 were studied by intracellular injection of lucifer yellow in the fixed-slice preparation. This corticocortical population contains primarily standard pyramidal cells, but occasional nonpyramidal, modified, fusiform, star, and inverted pyramidal cells were also seen. All cell types were present throughout layer 2 and in the upper and middle parts of layer 3. Standard pyramidal cells were found exclusively in lower layer 3. The mean somatic area of the area 17 projecting neurons was 251 microns 2. The width of basal dendritic fields was correlated to cell size for standard pyramidal cells but not for the other cell types. Next, the morphology and dendritic organization of the area 17 projecting neurons were compared to the pyramidal cells of the local horizontal patch networks and of the callosal system. The depth profile of the area 17 projecting and callosal pyramidal groups was virtually identical, peaking at 400 microns from the pial surface, whereas the local patch pyramidal group peaked at 281 microns. The local patch, area 17 projecting, and callosal pyramidal cells displayed increasingly larger mean somatic areas and basilar dendritic field width measurements. The number of basal dendritic branch points was greatest for callosal cells, and it was indistinguishable between local patch and area 17 projecting neurons. In the tangential plane, circular dendritic fields were observed on all callosal cells, but they were found on only approximately half of the local patch and area 17 projecting neurons. The remaining local patch and area 17 projecting neurons displayed mediolaterally and anteroposteriorly elongated basal dendritic fields, respectively.

Efferent projections of the posterior lateral line lobe in gymnotiform fish.

The posterior lateral line lobe (PLLL) of gymnotoid fish has efferent projections to two midbrain regions: the nucleus praeeminentialis dorsalis (n.P.d.) and the torus semicircularis dorsalis (T.Sd.). Both ipsilateral and contralateral connections are present; the n.P. d. receives nearly equal input from both sides while the T.Sd. receives a stronger contralateral input. The PLLL projection to n.P.d. merely maps medial PLLL to ventral n.P.d. and lateral PLLL to dorsal n.P.d., thus preserving the separate topography and relative orientation of the four electrosensory maps found in the PLLL. Only PLLL pyramidal cells (basilar and nonbasilar pyramids) contribute to this projection. The four PLLL electrosensory maps converge onto T.Sd. so that they map the dorsal body surface onto medial T.Sd. and the ventral body surface onto lateral T.Sd. Pyramidal cells, spherical cells, and multipolar cells contribute to this projection. A small commissural connection links homologous segments of the PLLL; these fibers arise from polymorphic cells of the PLLL.

Application of a simple culture of Plasmodium berghei for assessment of antiparasitic activity.

Mouse erythrocytes infected with Plasmodium berghei were incubated for a short period in microplate wells. The parasites changed morphologically from the immature ring form to mature schizonts, and free merozoites were released. However, reinvasion of the erythrocytes appeared not to be possible in this system. This intraerythrocytic one-step growth of the parasite could be determined quantitatively by counting incorporation of 3H-hypoxanthine. The incorporation was markedly decreased by addition of certain antiparasitic agents to the culture. The sensitivity of this growth inhibition test was comparable to or higher than the mouse protection test. The results suggested the practical utility of this simple assay in screening antimalarial activity.

Immunohistochemical investigations of neurofilament M' and alphabeta-crystallin in the magnocellular layers of the primate lateral geniculate nucleus.

The magnocellular and parvocellular pathways are two major processing streams in the primate visual system. Using high-density grid arrayed cDNA clones to hybridize to cDNA probes from cortical regions of each pathway, a list of candidate differentially expressed genes was produced [Mol. Brain Res. 82 (2000) 11-24]. Magnocellular pathway candidates include neurofilament M' and alphabeta-crystallin. Using antibodies generated against these proteins, immunohistochemical analysis revealed preferential staining of the magnocellular layers in the primate lateral geniculate nucleus, providing verification of two candidate magnocellular-enriched genes.

Metallothionein induction as a potent means of radiation protection in mice.

A striking resistance to lethal damage from a single dose of 6-8 Gy of X rays has been found in mice which had received various pretreatments to induce metallothionein (MT) synthesis in the liver prior to irradiation. Mice were injected with manganese (10 mg Mn/kg) or cadmium (3 mg Cd/kg) salt subcutaneously, or a patch of dorsal skin (2 X 2 cm2) was excised 1 or 2 days prior to irradiation. The increased tolerance of these mice to radiation was established by a marked decrease of mortality rate, an increase of mean survival time, a reduction of weight loss, and a smaller decrease in the number of leukocytes as compared with the control group. The LD50/30 for control mice was 6.3 Gy, while the corresponding values for the groups pretreated with Mn, Cd, and skin excision were 7.5, 7.7, and 7.9 Gy, respectively. The normal level of MT in mouse liver was approximately 25 micrograms/g tissue. This level increased 2.5- to 3-fold 24 h after 6.3 Gy irradiation. The MT levels of mice pretreated with Cd, Mn, and skin excision were increased 8-, 5-, and 7-fold, respectively, prior to irradiation as compared with the preirradiation control. These results indicate that the induction of MT in mouse liver is a significant factor in the mechanism of protection against radiation.

Immune effects of low-dose radiation: short-term induction of thymocyte apoptosis and long-term augmentation of T-cell-dependent immune responses.

We and others have shown that low-dose X or gamma irradiation of mice leads to an increase in their survival after a subsequent lethal high-dose irradiation. The greatest increase in radioresistance appears at a fixed window of dose and time, e.g. 8 weeks after 5-10 cGy or 2 weeks after 50 cGy preirradiation. We show that low-dose irradiation induces thymocyte apoptosis with a maximal level at 6 h postirradiation that returns to background levels after 24 h. At the same time, we observed no morphological alteration of splenocytes and no early modification of the intensity of T-cell-dependent immune responses as measured by plaque-forming cell (PFC) counts. Nevertheless, we found that PFCs were increased 2 weeks after 50 cGy irradiation, which is the same time at which mice expressed the optimal increase in survival after a second lethal irradiation. We also examined thymocyte apoptosis and spleen PFCs in mice subjected to other stress-inducing pretreatments. Our results emphasize the existence of a lag time between the time of low-dose irradiation in vivo and the appearance of radioresistance. A mechanism that interconnects an environmental stimulus with the response of the animal is proposed based on the evidence presented here and reported in the literature.

Traumatic aneurysm of the abdominal aorta with acute thrombosis of bilateral iliac arteries.

A traumatic aneurysm of the abdominal aorta resulting in acute peripheral thrombosis is rare. A 29-year-old man suffered a sudden occlusion of the terminal abdominal aorta and bilateral iliac arteries. An infrarenal abdominal aortic aneurysm was found, along with destruction of lumbar vertebrae and an aberrant renal artery. The pathogenesis of this false aneurysm was thought to be traumatic rather than inflammatory because the patient's history and laboratory findings showed no signs of inflammatory reactions. He had been in an automobile accident five years previously, resulting in lumbar vertebral injury. Arterial reconstruction and intraoperative perfusion of the aberrant renal artery were performed successfully. To our knowledge, our case is the seventh one reported in the English literature of a traumatic aneurysm of the abdominal aorta successfully repaired by surgery.

Calbindin D-28K immunoreactivity in the cat's superior olivary complex.

The calcium binding protein, calbindin D-28K (CaBP), was identified immunohistochemically in the cat's superior olivary nuclei. Intense somatic labeling was observed in the medial and lateral nucleus of the trapezoid body. The lateral superior olive contained dense, perisomatic, terminal bouton labeling surrounding unlabeled somata, while the medial superior olive exhibited the least amount of labeling, comprised only of a few fiber fragments.

Intrinsic connections in cat visual cortex: a combined anterograde and retrograde tracing study.

Area 18 of cat visual cortex was examined for intrinsic axons following small, columnar injections of an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L). Locally projecting axons radiated from the injection site and branched to form 10-15 discrete, approximately circular patches 500-750 microns in diameter consisting of many bouton-studded terminal arborizations. Labeled fibers and boutons ramified densely in layers I, II/II, V, and VI, and were noticeably less dense in layer IV. Afferent and efferent pathways originating from the same cortical columns were studied by injecting a mixture of PHA-L and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Between 10 and 15 patches of cells retrogradely labeled by WGA-HRP surrounded each injection site. Within a patch, labeled cells were found in all layers and included both pyramidal and non-pyramidal cells. The distribution of PHA-L labeling was similar to that obtained when PHA-L was injected alone. Most often, the labeled patches resulting from injections of such mixtures contained both anterograde and retrograde labeling. However, patches consisting of retrograde labeling alone and of anterograde labeling alone were also observed, indicating that the local connections linking neighboring cortical columns were not always reciprocal.

Presence of GABA-immunoreactive neurons within intracortical patches in area 18 of the cat.

In cat visual cortex, horizontal, intracortical connections spread laterally to link together specific columnar sites. When visualized by retrograde tracers, these intracortical connections appear as periodic, columnar patches of dense cellular labeling interspersed with areas of much less dense labeling. We looked for anatomical evidence for direct inhibition among the patchy, horizontal connections in area 18, by combining retrograde labeling using wheat germ agglutinin (WGA) conjugated to horseradish peroxidase (HRP) with immunohistochemistry using an antiserum against the inhibitory neurotransmitter gamma-amino butyric acid (GABA). We found numerous double-labeled cells associated with some, but not all, of the local patches nearest to the injection site. In the superficial layers, the GABA-immunoreactive cells also labeled with WGA-HRP were confined to a zone approximately 1.0 mm from the center of the injection, while the double-labeled cells in the deeper layers spanned greater distances, up to 3.0 mm from the injection center. These more distant, double-labeled cells in the deeper layers were located on the edges or outside of the patches of dense labeling. Thus, all of the more distant intracortical patches, as well as some of the more proximal patches were devoid of double-labeled cells--a finding which suggests that direct inhibition may occur among only a selected group of the 'short range' intracortical patches and among none of the long-range patches.

Input to the medullary pacemaker nucleus in the weakly electric fish, Eigenmannia (sternopygidae, gymnotiformes).

In order to identify which brain centers are involved in the control of electric organ discharge in electric fish, HRP was injected into the medullary electromotor (pacemaker) nucleus in the gymnotoid Eigenmannia. Neurons were retrogradely labeled in only a small nucleus of the mesencephalic tegmentum, herein called the prepacemaker nucleus. The prepacemaker nucleus lies just caudal and ventral to the posterior commissure and comprises at least two types of neurons.

Differential expression of neurofilament protein in the visual system of the vervet monkey.

It has been previously reported that the monoclonal antibody SMI-32 reveals a characteristic pattern of immunostaining which may be used to delineate various cortical modules in the monkey visual system. We wished to examine staining patterns with this antibody at both the lateral geniculate nucleus (LGN) and cortical levels with regard to magno- and parvocellular processing schemes in the vervet monkey. Using standard immunohistochemical procedures, we have found that the M-layers of the LGN were intensely stained in comparison to P-layers and that there were regional variations in staining within the visual cortex that reflected this input. The transition between areas V1 and V2 was especially prominent due to differences in the laminar staining profiles. Another striking result was found within the superior temporal sulcus where heavy SMI-32 immunostaining confined to the floor of the sulcus coincided with a similar zone of intense myelin staining. We have also found a number of other areas within the intraparietal and lateral sulci that show foci of heavy SMI-32 staining. As with Cat-301 immunostaining, the regional variabilities that are observed with SMI-32 in the visual cortex reflect molecular distinctions that may provide further criteria for functional segmentation.