Comparisons of dorsal and ventral hippocampus cornu ammonis region 1 pyramidal neuron activity during trace eye-blink conditioning in the rabbit.

Previous studies demonstrating a critical role of the hippocampus during trace eye-blink conditioning have focused primarily upon the dorsal portion of the structure. However, evidence suggests that a functional differentiation exists along the septotemporal axis of the hippocampus. In the present study, the activity of 2588 single cornu ammonis region 1 pyramidal neurons of the dorsal hippocampus and ventral hippocampus were recorded during trace and pseudo-eye-blink conditioning of the rabbit. Learning-related increases in dorsal hippocampus neuron firing rates were observed immediately prior to behavioral criterion, and increased over the course of training. Activation of dorsal hippocampus neurons during trace conditioning was also greater than that of ventral hippocampus neurons, including during the trace interval, in well-trained animals. An unexpected difference in the patterns of learning-related activity between hemispheres was also observed. Neurons of the dorsal hippocampus ipsilateral and contralateral to the trained eye, exhibiting significant increases in firing rate [rate increasing neurons], demonstrated the greatest magnitude of activation early and late in training, respectively. Rate increasing neurons of the dorsal hippocampus also exhibited a greater diversity of response profiles, with 69% of dorsal hippocampus rate increasing neurons exhibiting significant increases in firing rate during the conditioned stimulus and/or trace intervals, compared with only 8% of ventral hippocampus rate increasing neurons (the remainder of which were significantly responsive during only the unconditioned stimulus and/or post-unconditioned stimulus intervals). Only modest learning-related activation of ventral hippocampus neurons was observed, reflected as an increase in conditioning stimulus-elicited rate increasing neuron response magnitudes over the course of training. No differences in firing rate between dorsal hippocampus and ventral hippocampus neurons during a 1-day pre-training habituation session were observed. Thus, dorsal hippocampus activation is more robust, suggesting a more substantial role for these neurons in the processing of temporal information during trace eye-blink conditioning.

Soft-tissue sarcomas of the shoulder girdle: factors influencing local recurrence distant metastases, and survival.

BACKGROUND: Prognostic factors and the role of radiotherapy have not been well characterized for soft-tissue sarcomas (STS) of the shoulder girdle. METHODS: The cases of 70 patients with primary shoulder STS were reviewed for the following information: size, grade and histology of tumors, extent of resection, and use of adjuvant radiotherapy. The influence of these factors on local disease-free survival (LDFS), distant disease-free survival (DDFS), and overall survival (OS) rates was analyzed using univariate analysis. RESULTS: With a median follow-up of 108 months, the overall 5- and 10-year survival rates for patients with shoulder girdle STS were 82% and 80%, respectively, whereas the 5-year disease-free survival rate was 63%. There were 25 (35%) tumor recurrences: 12 (17%) distant and 13 (18%) local regional. Tumors > 5 cm in size were associated with a significantly decreased 5-year OS rate compared with lesions < 5 cm, and high-grade tumors were associated with significantly decreased DDFS and OS rates. Because most of the patients who underwent amputation had large, high-grade tumors, they had significantly decreased 5-year DDFS and OS rates compared with wide local excision. Radiotherapy produced a significant improvement in LDFS rates, particularly in patients with tumors > 5 cm in size. CONCLUSIONS: The results indicate that both tumor size and grade are important prognostic factors in shoulder girdle STS. Adjuvant radiotherapy should be considered in large tumors to improve the LDFS and to decrease the need for radical ablative surgery.

The N30 component of somatosensory evoked potentials in patients with dystonia.

We recorded short-latency median nerve somatosensory evoked potentials (SEPs) in 10 patients with dystonia (6 with focal dystonia, 3 with generalized dystonia, and 1 with segmental dystonia) and compared them with those of 10 normal controls. The EEG was recorded from 29 sites on the scalp with linked earlobe electrodes for reference. Latencies and amplitudes of P15, postcentral N20 and P45, and frontal N30 were evaluated. The latencies of all potentials were the same in patients and controls. The amplitudes of P15, N20 and P45 were also the same in both groups, but the N30 amplitude of the patients was larger than of the controls. The amplitude of N30 did not vary from the affected side to the unaffected side. Previous work has shown decreased N30 amplitude in patients with Parkinson's disease. Changes in N30 amplitude may be indicative of abnormal excitatory effects on cortex resulting from disorders of the basal ganglia.

Small intestinal transit in the portal hypertensive rat.

The purpose of this study was to determine the effects of portal hypertension on gastrointestinal transit. Portal hypertension was induced in a group of 15 rats by the staged portal vein ligation technique. A control group of 15 rats underwent a sham operation. Ten days later, a 51Cr-labeled Krebs' buffer solution was instilled into the duodenum and the distribution or radioactivity along the length of the small intestine was determined after 15, 30, and 60 minutes. Portal hypertension was consistently established in the study group; splenic pulp pressure (mm Hg, mean +/- SD, portal hypertensive vs. control) was 20.0 +/- 3.9 vs. 12.7 +/- 3.9, P less than 0.002. Various measures of intestinal transit revealed delayed transit in the portal hypertensive group. Retention of radioactivity in the most proximal quartile of the intestine was greater [percentage retained (portal hypertensive vs. control) was 57.9 +/- 17.3 vs. 31.2 +/- 15.3, P less than 0.02, 49.1 +/- 15.5 vs. 28.3 +/- 4.8, P = 0.03, and 42.4 +/- 17.6 vs. 29.0 +/- 8.8, P = 0.08, at 15, 30, and 60 minutes, respectively] and the geometric mean of transit was located more proximally (P less than 0.02) at each study interval in the portal hypertension group. It was concluded that portal hypertension is associated with delayed intestinal transit. This abnormality could predispose to bacterial overgrowth and contribute to altered digestion and absorption.

Pervasiveness and magnitude of context effects: evidence for the relativity of absolute magnitude estimation.

To test the assertion that absolute magnitude estimation serves to minimize context effects, two experiments were conducted in which area stimuli were judged under differing conditions. In Experiment 1, four groups of subjects made magnitude estimations of triangles ranging in area from 1.5 to 3,072 cm2. No standard or modulus was used, and instructions were similar to those used in absolute magnitude estimation experiments. Each group first judged a different subrange of the stimuli (1.5-24; 48-768; 6-96; or 192-3,072 cm2) before making judgments of the remaining stimuli. In Experiment 2, two groups of subjects made magnitude estimations of triangles ranging in area from 1.5 to 12,288 cm2, with each group first judging a different subrange of stimuli (1.5-24 cm2 or 768-12,288 cm2). The design and instructions were virtually identical to those used in absolute magnitude estimation experiments. Our results indicate that the wording of the instructions is not crucial and that judgments are influenced in two ways that are not predicted by proponents of absolute magnitude estimation. First, the power functions fit to the initially presented subranges (e.g., 1.5-24 cm2), which were judged without contextual effects produced by previously presented stimuli, were inconsistent with one another. Second, judgments of the remaining stimuli were influenced by the subrange of stimuli judged initially. The prevalence of context effects in both experiments, in spite of instructional differences, suggests that although one should avoid using a standard and modulus, there is little else to be gained by adopting the absolute magnitude estimation procedure.

Topography of movement-related cortical potentials is abnormal in Parkinson's disease.

We studied the scalp-recorded, movement-related cortical potentials occurring immediately before and after the onset of movement in 5 patients with asymmetric Parkinson's disease. The topographic distribution of the initial slope of motor potential (isMP) was diffuse for voluntary finger movements of the more affected hand but normal for movements of the less affected hand. The frontal peak of motor potential (fpMP) was located more posterior in patients than in normal subjects. The peak amplitudes of the potentials were normal in all patients. The topographic abnormalities might reflect inadequate excitatory activity from the basal ganglia to the primary motor cortex and the supplementary motor area.

Gastric emptying of liquids and solids in the portal hypertensive rat.

The effects of portal hypertension on gastric motor function were investigated using the rat staged portal vein ligation model. Gastric emptying of liquids and solids was studied separately following meals labeled with 51Cr or 99Tc by whole stomach scintillation counting. Portal hypertension was consistently established in experimental rats (splenic pulp pressure: mean +/- SEM, portal hypertension versus control, 16.8 +/- 0.7 vs 11.8 +/- 0.7 mm Hg, P less than 0.0001). Although liquids were emptied in an exponential manner and solids in a linear fashion, gastric emptying of both meals was more rapid in the experimental rats. Ten minutes after the liquid meal, more than 50% of the meal had emptied from the stomachs of portal hypertensive rats while only one third of the meal had cleared in the control group (P less than 0.02). Gastric emptying of the solid meal was significantly accelerated in experimental rats at 60 and 120 min (percent meal remaining: portal hypertension versus control, 41.9 +/- 4.0 vs 55.4 +/- 3.5 and 21.5 +/- 4.9 vs 32.6 +/- 4.3, P less than 0.05). Stomachs of portal hypertensive animals were heavier (P less than 0.009) and histologic examination revealed submucosal edema. Thus, a possible mechanism of the disrupted gastric motor function in portal hypertension is decreased gastric wall compliance secondary to edema.

Energy-related neurotoxicity at the NMDA receptor: a possible role in Alzheimer's disease and related disorders.

Using rat cerebellar granule cells in primary culture as our model system, we have shown that excitatory amino acids (EAAs) become neurotoxic via the NMDA (N-methyl-D-aspartate) receptor when neuronal energy levels are compromised. Omission of glucose, exclusion of oxygen, or inclusion of inhibitors of oxidative phosphorylation or of Na+/K+-ATPases enables NMDA receptor agonists to express their neurotoxic potential. Both competitive and noncompetitive NMDA receptor antagonists are potent blockers of EAA neurotoxicity, with MK-801 fully effective at 20 nM. We interpret these results as indicating that glucose metabolism, ATP production, and functioning ion pumps are necessary to generate a resting potential sufficient to maintain the voltage-dependent Mg++ block of the NMDA receptor channel; relief of the block enables EAAs to act persistently at the NMDA receptor causing an excessive ion influx which leads to neuronal death by a mechanism not yet understood. These findings are discussed in the context of the potential role for NMDA receptor-mediated neurotoxicity in Alzheimer's disease and related disorders.

Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor appears to play a pivotal role in enabling glutamate to express its neurotoxic potential in a variety of neurological disorders. Our results show that the transition of glutamate from neurotransmitter to neurotoxin is facilitated when cellular energy is limited in cultured cerebellar neurons. Omission of glucose, exclusion of oxygen, or inclusion of inhibitors of oxidative phosphorylation or of the sodium/potassium pump, enables the excitatory amino acids glutamate or NMDA to express their neurotoxic potential. We interpret these results as demonstrating that glucose metabolism, ATP production, and functioning Na+,K+-ATPases are necessary to generate a resting potential sufficient to maintain the voltage-dependent Mg2+ block of the NMDA receptor channel; relief of the Mg2+ block enables the excitatory amino acids to act persistently at the NMDA receptor, resulting in the opening of ion channels and subsequent neuronal damage. These findings are discussed in the context of perturbations or abnormalities which lead to decreased availability or utilization of glucose and oxygen in the brain which may trigger endogenous excitatory amino acids to become neurotoxic by this mechanism.

Antigens of Streptococcus mutans implicated in virulence--production of antibodies.

The present studies assayed antibody activities in serum and saliva of animals immunized by different routes, with cells of S. mutans or cell-free preparations containing GTF, FTF, LTA and/or dextranase synthesized by S. mutans. The results show that the type of immunogenic preparation and the route of its administration can elicit different antibody response and may in part explain the disparity of results achieved by different investigators. The results further emphasize the need to use standardized preparations and carefully described protocols for vaccination.

Adsorption of Streptococcus mutans lipoteichoic acid to hydroxyapatite.

Lipoteichoic acid extracted from cells of S. mutans strain BHT exhibited a high affinity for hydroxyapatite. Phosphate ions, fluoride ions and to a lesser extent human saliva inhibited or reversed this adsorption. Extracellular lipoteichoic acid preparations obtained from the supernatant of cultures of the same bacteria exhibited similar properties. It is suggested that lipoteichoic acids could play a significant role in the colonization of teeth by Gram-positive bacteria and thereby contribute to the formation and pathogenicity of dental plaque.

Granulocyte harvest for transfusion: donor response to repeated leukapheresis.

Leukapheresis of normal donors with the NCI-IBM Continuous Flow Blood Cell Separator was compared with the method of filtration leukapheresis. An average of 5.7 times 10-9 (range 1.4 to 10.9 times 10-9) granulocytes were collected on 25 occasions with the blood cell separator compared with an average of 36.6 times 10-9 (range 20.1 to 61.3 times 10-9) obtained by filtration leukapheresis on 85 occasions. Donor platelet counts decreased following donation by an average of 29,000/mul (14%) with continuous flow centrifugation (CFC) and an average of 40,000/mul (17%) with filtration leukapheresis (FL). Estimated donor packed red blood cell loss, including blood obtained for investigative purposes, was 80 ml per donation with CFC and 67 ml per donation when FL was used. FL resulted in at least a 25 per cent increase in the granulocyte count of donors by donation completion in 61 per cent of donors, although postdonation granulocytosis did not correlate with increased cell harvest. CFC donors generally displayed a postdonation decrease in granulocyte count. Normal numbers of granulocytes were maintained in donors undergoing frequent leukapheresis and no donor's health was compromised by the removal of large numbers of granulocytes. Repeated donations were possible with both systems. Although platelet counts dropped more with FL, the procedure was performed as frequently as eight times in a ten-day period without development of severe donor thrombocytopenia. Donor red blood cell loss appears to be the limiting factor in the repeated use of either system. Blood loss could be significantly decreased under routine conditions if fewer samples were obtained for investigational purposes. Filtration leukapheresis offers the advantage of significantly greater granulocyte yields than is possible with CFC unless modifications such as arterio-venous shunts or the use of steroids and/or rouleaux-inducing agents are employed.