Ganglioside or sialic acid attenuates ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature.

1. This laboratory has previously reported that pretreatment with ganglioside, or even with its constituent, sialic acid (SA), can attenuate certain intoxicating effects of ethanol. It was important to see if these findings could be replicated, particularly by using other measures of ethanol effects. Herein we report that pretreatment with either gangliosides or SA attenuated ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature. 2. An ethanol dose of 4 gm/kg caused a temperature drop of about 3 degrees C, which was unaffected by any pretreatment. The onset to sleep, however, was delayed an average of 18 or 36 secs in mice pretreated with ganglioside or SA, respectively. Ethanol-only (4 gm/kg) depressed mean cumulative locomotor activity to 31% of normal, whereas the depression was 83% of normal with beef brain ganglioside pretreatment. At 2 gm/kg ethanol alone decreased nose poking in a hole-board test to 29% of normal, but the depression was only 55-63% of normal with SA or ganglioside pretreatment. In a staircase climbing anxiety test, this dose of ethanol had no effect by itself, but both ganglioside and SA pre-treatment increased climbing by 22%. Ethanol did depress rearing to only 11% of normal, whereas rearing was 51 and 99% of normal with SA and ganglioside pretreatment, respectively. In a dark-preference test, ethanol-only caused mice to spend 64% of the time in the light, compared to 31% for controls. Time in the light was only 39 and 46% with ganglioside and SA pretreatment, respectively. 3. Blood levels of ethanol were not significantly affected by pretreatment. 4. When given alone, gangliosides significantly stimulated locomotion and staircase climbing. SA significantly decreased rearing in the staircase test. Both gangliosides and SA tended to increase nose poking, number of crossings in the dark-preference test, and time in a lighted compartment. Thus, it is possible that some of the attenuation of intoxication is attributable to non-specific stimulant properties of gangliosides and SA.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Isolation of a rat S100 alpha cDNA and distribution of its mRNA in rat tissues.

In order to clarify the reported discrepancies in S100 alpha protein and mRNA distribution in rat tissues, a rat S100 alpha cDNA has been isolated and this species homologous probe along with a rat S100 beta cDNA probe has been used to examine S100 mRNA expression in rat tissues. Although the rat S100 alpha cDNA was missing approximately 30 nucleotides of coding sequence, only 4 conservative changes in amino acid sequence were observed when the deduced amino acid sequence was compared to the bovine S100 alpha amino acid sequence. Thus, S100 alpha proteins, like S100 beta proteins, are highly conserved among species. All nineteen of the tissues examined (including cerebrum and cerebellum) contained S100 alpha mRNA. In addition, S100 beta mRNA was detected in thirteen of the nineteen tissues examined. These results are in agreement with previous protein distribution studies and further demonstrate that S100 proteins are not brain-specific and are expressed in a large number of tissues. Although S100 alpha and S100 beta mRNAs were detected in rat tissues which had previously been reported to contain S100 alpha and S100 beta protein, a direct correlation between the protein and mRNA levels were not observed, suggesting that different mechanisms regulate S100 expression in various tissues. S100 alpha exhibited a single similar size mRNA species (0.5 Kb) in all tissues examined, as did S100 beta (1.5 Kb), suggesting that the individual S100 proteins are expressed as single mRNA and protein products in rat tissues.     

Physiological responses of typical versus heavy weight triathletes to treadmill and bicycle exercise.

A physiological comparison of the responses of typical weight (less than 90 kg) versus heavy weight (greater than 90 kg) male triathletes to maximal treadmill and maximal bicycle exercise was performed to better understand the effects of weight on endurance performance. The heavy triathlete group (90.9 +/- 3.2 kg, mean +/- SD) had significantly (p less than .01) greater percent body fat (11.9 +/- 3.6 vs 7.4 +/- 1.8%) while having significantly (p +/- .01) lower VO2max values expressed in ml.kg-1.min-1 on both the treadmill (55.6 +/- 4.1 vs 69.9 +/- 5.5) and bicycle ergometer (51.9 +/- 3.9 vs 60.5 +/- 6.2) than the typical triathlete group (66.6 +/- 5.9 kg). Analysis of covariance using body fat as the covariate resulted in persistent significant (p less than .02) VO2max (ml.kg-1.min-1) differences between the groups. Statistically significant (p less than .05) differences in running economy existed between the groups (33.7 +/- 2.7 vs 37.1 +/- 1.5 ml.kg-1.min-1; typical vs heavy). The heavy triathletes also had a significantly (p less than .01) shorter treadmill performance time (9.6 +/- 2.3 vs 13.2 +/- 1.7 min) and significantly (p less than .01) lower power per weight ratio on the bicycle ergometer (5.37 +/- 0.48 vs 6.47 +/- 0.59 watts/kg). These findings indicate that the heavy triathlete is at a physiological disadvantage when competing in endurance events and supports the inclusion of a weight category in these events. The reported triathlon results support these physiological findings.     

Temporomandibular joint eminence augmentation by down-fracture and inter-positional cartilage graft. A new surgical technique.

A new surgical technique for the treatment of recurrent temporomandibular joint subluxation or dislocation is described. Following a horizontal osteotomy and down-fracture of the articular eminence an inter-positional bovine cartilage xenograft is inserted in order to augment the vertical height of the eminence. The procedure combines simplicity with minimal post-operative morbidity. The increase in eminence height is both predictable and stable.     

Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggests no spontaneous activity of cochlear origin

Deafness mutant mice show no stimulus-related cochlear potentials as well as abnormal electrically-evoked responses recorded from the inferior colliculus. Abnormal spontaneous activity in the auditory periphery could result in abnormal development and/or maintenance of the central auditory pathways. We therefore assessed spontaneous activity of cochlear origin in the central nuclei of the mutants by ablating one cochlea and subsequently using the 2-deoxyglucose (2DG) technique to study metabolic activity. Any asymmetries in labeling in a given nucleus should be due to spontaneous activity in the cochlear nerve on the unoperated side. In control animals (+/dn mice undergoing unilateral cochlea ablation), statistically significant decreased 2DG labeling was observed in the ipsilateral PVCN and AVCN, and contralateral MNTB and IC; all receive primary excitatory input from the ablated ear. No significant differences in labeling between right and left sides were observed in any of the nuclei studied in the mutant animals. These findings suggest that there is no spontaneous activity of cochlear origin in these mutants, even though many cochlear nerve fibers and spiral ganglion cells survive.     

Microscopic endonasal surgery of the paranasal sinuses and the parasellar region

The anatomic principles and operative techniques currently applied to functional endoscopic endonasal surgery have allowed for significant refinements in another approach to regional pathology that uses the operating microscope, newly designed sinus instruments, and a self-retaining nasal speculum system. The main benefits of this method are the superb widefield stereoscopic vision and the distinct freedom to work bimanually. Additionally, direct bipolar cautery of bleeders is afforded while use of the observer tube or video allows for excellent teaching. The precise nature of this surgery affords less fear of serious complications in the treatment of periorbital, paranasal sinus, and parasellar diseases. We describe technical aspects of the surgery and associated complications in 219 patients treated from 1984 to 1987.     

Family history evaluation as a predictive screen for childhood hypercholesterolemia. Pediatric Practice Research Group

A study was conducted to evaluate the efficacy of family history factors as screening criteria for childhood hypercholesterolemia. When they were seen for routine care at one of eight office practices, 1005 prepubertal children underwent random serum cholesterol determinations. Parental and grandparental histories of cardiovascular risk factors and atherosclerotic complications prior to 55 years of age were also obtained. Of the initial group, 274 children had total cholesterol levels greater than or equal to 175 mg/dL, and 175 of these children returned for retesting after an overnight fast. A total of 88 children were found to have low-density lipoprotein-cholesterol (LDL-C) values greater than or equal to 90th percentile for age and sex. Maternal and paternal histories of hypercholesterolemia were significantly associated with elevated LDL-C (odds ratio = 7.3 and 2.9, respectively), but had extremely low sensitivities (0.09, 0.15) despite modest positive predictive values (0.42, 0.22). Grandparental histories of sudden death, peripheral vascular disease, and gout were associated with elevated LDL-C, but sensitivities and positive predictive values for all of these factors were less than 0.22. Family history factors most commonly recommended as criteria for cholesterol screening in children did not identify half of all the children with elevated LDL-C and did not selectively identify the most severely affected children. Adding information concerning the presence of childhood obesity did not result in appreciable improvement in LDL-C detection beyond that achieved by family history factors alone. It was concluded that if thorough identification of young children with elevated LDL-C is desired, inclusive population screening rather than a family history-based strategy would be the most effective approach.     

Epidemic measles in an isolated unvaccinated population, India

Between June and September, 1986, an outbreak of measles occurred in Pilkhi Primary Health Centre area (population 56,000) in Tehri Garhwal district, Uttar Pradesh, India. Overall, 1092 cases were identified and 62 died; case-fatality ratio was 5.7%. Illness was restricted primarily to children below 15 years of age; 38% cases were in children under 5 and 58% between 5-14 years of age. To better characterize the outbreak, a survey was conducted in 13 affected villages. The age of the cases ranged from 5 months to 19 years (median = 7.0 years). The age-specific attack rates were 22.4%, 54.5%, 46.2% and 35.3% for children under 1, 1-4, 5-9, 10-14 years of age respectively. In as many as four villages, the attack rate in children below ten was 80% or more. Secondary attack rate among family members was 70%. Overall, 82% of children with measles developed complications which consisted mainly of pneumonia, diarrhoea and dysentery. The age-specific case-fatality ratios in infants and children 1-4 years of age were 23.1% and 11.5% respectively; thereafter the rates tended to decline with increasing age and was higher in females than in males (less than 0.05). Pneumonia which was a complication in 39% of measles cases contributed to 56% of deaths. Traditional beliefs and customs in the area were strong and did not encourage treatment of measles cases. Although a measles vaccination programme has been launched in India since 1985, only 30 districts could be covered during the first year and another 90 during 1986.(ABSTRACT TRUNCATED AT 250 WORDS)