Inhibitory synaptogenesis in mouse somatosensory cortex

It is widely believed that inhibitory synapses are not present or present in only small numbers in the rodent cerebral cortex during the early postnatal period when the cortex is being innervated by thalamocortical fibers. Quantitative electron microscopy was carried out on the posteromedial barrel subfield of mouse somatosensory cortex from postnatal day 4 (P4) when thalamocortical innervation of the barrels is becoming established, through to sexual maturity (>P32), and in adulthood. Both asymmetrical (putatively excitatory) and symmetrical (putatively inhibitory) synapses were present in all layers from P4. The symmetrical synapses were immunoreactive for GABA at all ages. There was a progressive increase in both asymmetrical and symmetrical synapses up to P32, density in all layers increasing 16-fold, with the production of asymmetrical synapses leading and greatly outstripping that of symmetrical. From P32 to P120, the oldest age studied, synaptic numbers declined by 18% to 13 times the P4 level, but this affected predominantly layers II/III, IV and V, and mainly involved asymmetrical synapses. The relative percentage of asymmetrical to symmetrical synapses from P4 to P8 was 57%/43% but at P32 it was 89.5%/10.5% and in adulthood 85.4%/14.6%. These data indicate that inhibitory synaptogenesis in the rodent cortex begins earlier than previously thought, a basis for inhibition being present from the earliest period. Pruning of all synapses occurs well after thalamocortical innervation is established and inhibitory synapses are less affected by the pruning process.      

Comparison of chewing cycles in 2-, 3-, 4-, and 5-year-old normal children

Chewing movements of normal 2-, 3-, and 4-year-old children were measured. Chewing movements of 2- and 3-year-olds were compared with those of 4- and 5-year-olds. Measures were taken on 56 children: 17 were 2 years old (8 female, 9 male); 19 were 3 years old (10 female, 9 male); and 20 were 4 years old (10 female and 10 male). Data of twenty 5-year-olds (10 males, 10 females) were taken from a previous study (9). Chewing movements were measured by time (seconds), number of cycles, and a time/cycle ratio. A chewing cycle was defined as an upward and downward movement of the chin. Total time from the moment food was placed in the mouth until the final swallow occurred was divided by the number of cycles counted for the same period. The type of food eaten affected time, cycles, and the time/cycle ratio, but age and sex did not. A comparison of younger (2- and 3-year-olds) and older children (4- and 5-year-olds) showed significant time differences. During maturation, time was shortened. It was shown earlier that under pathologic conditions (Down's syndrome) time was prolonged. Thus, the time/cycle ratio is an excellent indicator of the developmental status of a child.     

Functional Oral-Motor Skills: Do They Change with Age?

Dysphagia, a difficulty eating or drinking, appears to increase with age and is a concern for our growing elderly population. Mastication, tongue mobility, and lip closure are skills of the oral phase of ingestion, and have been shown to deteriorate with age. However, it is not clear whether these changes affect functional feeding. It is also unclear whether dysphagia is the result of the aging process itself, or whether it is secondary to disease. Therefore, the purpose of this study was to identify changes during the oral phase of ingestion in a group of healthy seniors. Functional feeding skills and oral praxis abilities were measured in 79 healthy adults aged 60–97 years. The Modified Functional Feeding Assessment (FFAm) subscale of the Multidisciplinary Feeding Profile (MFP) and the Oral Praxis Subtest (OPS) of the Southern California Sensory Integration Test were administered respectively. An interview followed to obtain information on denture wear, use of hearing aids and glasses, and types of foods avoided. Seniors maintained functional feeding skills throughout the four decades studied. These skills were not age-dependent, but depended on whether or not subjects wore full dentures. Even though all of the seniors maintained functional feeding skills, more seniors in the younger group (7th decade 60%, 8th decade 67%) had difficulty with a variety of food textures such as soft, hard, fibrous, and some with tough skins, than the older group (9th decade 40%, 10th decade 44%). Oral praxis abilities were correlated significantly with age, but not with hearing aid use. Overall, healthy seniors maintained their functional feeding and oral praxis skills. Good health and natural dentition appear to be excellent indicators for functional feeding ability.     

Tailored hormonal therapy in secretory adrenocortical cancer

Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone     

Effect of oral sensorimotor treatment on measures of growth and efficiency of eating in the moderately eating-impaired child with cerebral palsy

Thirty-five children with cerebral palsy and moderate eating impairment were studied to determine the effect of oral sensorimotor treatment (OST) on eating efficiency and measures of growth (weight gain). After taking effects of maturation into account, 11 children who received OST (group A) exceeded their expected centile line by 1.7 percentile points after 10 weeks of treatment. Chewing exercises alone (group B) had no effect on weight gain. Although small decreases occurred in the time needed to eat three standard textures of food (solid, viscous, puree) in groups A and B, these were not significant. Children maintained their weight-for-age percentile line although at the lower end of expected norms. These children will be at risk of growth failure because of the increased energy demands once they enter their teenage growth spurt. The clinical implications of these findings are that prolonged mealtime and oralmotor therapies may be adequate through the childhood years. Thereafter, children's growth must be monitored carefully, and oral caloric supplementation is suggested to provide the necessary energy for growth.     

Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells

Human endothelial cells release two forms of a plasminogen activator- specific inhibitor: an active form that readily binds to and inhibits plasminogen activators and an inactive or latent form that has no anti- activator activity but which can be activated by denaturation. Latent and active forms of plasminogen activator-specific inhibitor were measured in cultures of human umbilical vein endothelial cells. Latent inhibitor was activated by treatment with 1% sodium dodecyl sulfate (SDS), and both forms were assayed by the 125I-fibrin plate method. After 16 hours, the conditioned medium contained 104.6 U/mL latent inhibitor activity and 2.6 U/mL active inhibitor. The level of each form in the culture medium increased with time although the activity associated with the latent form rose more rapidly: the ratio of latent to active inhibitor activity was 12 at four hours (10.3 U/mL v 0.86 U/mL) and reached 56 at 24 hours (155.3 U/mL v 2.80 U/mL). Intracellular inhibitor activity was associated with the active form only; no additional inhibitor activity was observed following SDS treatment of cell extracts. A decline in active inhibitor activity occurred during incubation at 37 degrees C with a 50% reduction in activity occurring in two hours. Treatment of conditioned medium with 10 U/mL thrombin also resulted in a loss of active inhibitor activity. The latent inhibitor, however, was not affected by either of these conditions. The inhibitor activity lost during incubation at 37 degrees C or thrombin treatment could be regenerated by SDS treatment, suggesting that the loss of the active inhibitor activity represented a conversion of this form to its latent counterpart. Thus, the concentration, stability, and regulation of these two forms of plasminogen activator inhibitor in human endothelial cell cultures differ significantly.     

Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients

Initial studies have shown that recombinant human interleukin-6 (rhIL- 6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment.     

Demonstration of single chain urokinase-type plasminogen activator on human platelet membrane

Fibrinolytic activity was found to be associated with sonicated platelet membranes after separation from cytosol by differential centrifugation. This fibrinolytic activity was attributed to the presence of a plasminogen activator, which was immunochemically identified as urinary-type plasminogen activator (uPA) by antibody neutralization assay, immunoblotting, and immunofluorescence. The molecular weight (mol wt) of this uPA was 54,000 and was present as the single chain form, although a small amount was detected in a higher mol wt complex indicative of a uPA-inhibitor complex. Treatment of membrane preparations with Triton X-100, 3 mol/L KCl, and 0.1 mol/L glycine, (pH 2.3), but not 10 mmol/L ethylenediamine tetraacetic acid (EDTA), removed the uPA from the membrane. This suggests that uPA is a peripheral membrane protein and that metal ions do not mediate protein- membrane association. Immunofluorescent staining revealed the presence of uPA on the outer surface of the platelet in preparations of intact unstimulated platelets. Thus, uPA is associated with the outer leaflet of the platelet membrane and may be involved with the acceleration of thrombus degradation observed with platelet-rich thrombi.