Anion modulation of taste responses in sodium-sensitive neurons of the hamster chorda tympani nerve

Beidler's work in the 1950s showed that anions can strongly influence gustatory responses to sodium salts. We have demonstrated "anion inhibition" in the hamster by showing that the chorda tympani nerve responds more strongly to NaCl than to Na acetate over a wide range of concentrations. Iontophoretic presentation of Cl- and acetate to the anterior tongue elicited no response in the chorda tympani, suggesting that these anions are not directly stimulatory. Drugs (0.01, 1.0, and 100 microM anthracene-9-carboxylate, diphenylamine-2-carboxylate, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonate, and furosemide) that interfere with movements of Cl- across epithelial cells were ineffective in altering chorda tympani responses to 0.03 M of either NaCl or Na acetate. Anion inhibition related to movements of anions across epithelial membranes therefore seems unlikely. The chorda tympani contains a population of nerve fibers highly selective for Na+ (N fibers) and another population sensitive to Na+ as well as other salts and acids (H fibers). We found that N fibers respond similarly to NaCl and Na acetate, with spiking activity increasing with increasing stimulus concentration (0.01-1.0 M). H fibers, however, respond more strongly to NaCl than to Na acetate. Furthermore, H fibers increase spiking with increases in NaCl concentration, but generally decrease their responses to increasing concentrations of Na acetate. It appears that anion inhibition applies to taste cells innervated by H fibers but not by N fibers. Taste cells innervated by N fibers use an apical Na+ channel, whereas those innervated by H fibers may use a paracellularly mediated, basolateral site of excitation.     

Ultrastructural and biochemical changes of hepatocytes during ether and fluothane anesthesia under experimental conditions

A study was made of a possibility of using Soviet made membranes "Vladipor" with a pore diameter of 16--17 nm for the purpose of concentration and purification of antigenic extracts from stab cultures of S. typhi obtained by the action of typsin, hydrogen peroxide and detergents. Preparations, complete by antigenic structure, were obtained by ultrafiltration, with a good yield. The maximal rate of ultrafiltration was noted in case of "peroxide" antigenic preparations. The use of diafiltration provided a significant reduction of the ash content in the end products.     

Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase

The four isomers of 4-aminopyrrolidine-2,4-dicarboxylate (APDC) were prepared and evaluated for their effects at glutamate receptors in vitro. (2R,4R)-APDC (2a), an aza analog of the nonselective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3R)-ACPD, 1), was found to possess relatively high affinity for metabotropic glutamate receptors (mGluRs) (ACPD-sensitive [3H]glutamate binding IC50 = 6.49 +/- 1.21 microM) with no effects on radioligand binding to NMDA, AMPA, or kainate receptors up to 100 microM. None of the other APDC isomers showed significant mGluR binding affinity, indicating that this interaction is highly stereospecific. Both 1 and 2a were effective in decreasing forskolin-stimulated cAMP formation in the adult rat cerebral cortex (EC50 = 8.17 +/- 2.21 microM for 1; EC50 = 14.51 +/- 5.54 microM for 2a); however, while 1 was also effective in stimulating basal tritiated inositol monophosphate production in the neonatal rat cerebral cortex (EC50 = 27.7 +/- 5.2 microM), 2a (up to 100 microM) was ineffective in stimulating phosphoinositide hydrolysis in this tissue preparation, further supporting our previous observations that 2a is a highly selective agonist for mGluRs negatively coupled to adenylate cyclase. Microelectrophoretic application of either 1 or 2a to intact rat spinal neurons produced an augmentation of AMPA-induced excitation (95 +/- 10% increase for 1, 52 +/- 6% increase for 2a). Intracerebral injection of 1 (400 nmol) produced characteristic limbic seizures in mice which are not mimicked by 2a (200-1600 nmol, ic). However, the limbic seizures induced by 1 were blocked by systemically administered 2a in a dose-dependent manner (EC50 = 271 mg/kg, ip). It is concluded that (2R,4R)-APDC (2a) is a highly selective, systemically-active agonist of mGluRs negatively coupled to adenylate cyclase and that selective activation of these receptors in vivo can result in anticonvulsant effects.     

Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory

Osteoporotic fractures, and in particular, hip fractures result in significant morbidity and mortality. Low bone mass is the main risk factor of enhanced bone fragility, resulting in an increased risk for hip fracture. Bone density of osteoporotic women with and without hip fractures show a considerable overlap. Therefore, other bone-independent factors also play an important role for the development of hip- and other osteoporotic fractures. One other important factor is falling. In 90% of hip fractures falling was involved [10-15], but only 5% or less of these falls resulted in a subsequent fracture. The view that adequate exercise is beneficial for skeletal health of children and for prevention and treatment of osteoporosis in adults is supported primarily by two lines of evidence: longitudinal and cross-sectional trials in children and young adult athletes showing a significant increase of muscle- and bone mass after strenuous (children) or chronic exercise (athletes) as compared to normally active (children) or sedentary control subjects. What are the potential benefits and limits of specific exercise programs with respect to bone mass, prevention of falls and fractures? In this review these questions are discussed and a specific exercise program in osteoporotic patients with fractures is delineated.     

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes

Twenty-two cases of ameloblastoma and ten cases of adenomatoid odontogenic tumour (AOT) were analyzed comparatively by the AgNOR technique. Ameloblastomas were distributed into three groups according to their clinical behaviour: primary lesions without recurrences (PLWTR), 5 cases; primary lesions with recurrences (PLWR), 4 cases; and recurrences, 13 cases. The cases were also regrouped according to their histological pattern: follicular (9 cases), plexiform (7 cases), acanthomatous (4 cases) and unicystic (2 cases). Considering histological patterns, there was a significant statistical difference only between follicular and plexiform types. There were no significant differences between the group of ameloblastomas and the group of AOTs or between the three groups of ameloblastomas with different clinical behaviour. Our results strongly suggest that the distinct clinical behaviour of ameloblastomas and AOT is not correlated with their cellular proliferation ratio. Thus, the infiltrative ability of the ameloblastomas is probably not related to the cellular proliferation index of these tumours.     

A study of the diagnostic accuracy and reliability of the Scoliometer and Adam's forward bend test

STUDY DESIGN: Study of the diagnostic accuracy and interexaminer reliability of scoliosis diagnostic tests. OBJECTIVES: To estimate the sensitivity, specificity, and predictive value of the Scoliometer (National Scoliosis Foundation, Watertown, MA) and Adam's forward bend test in diagnosing scoliosis, and to determine the interexaminer reliability of the Scoliometer and Adam's forward bend test. SUMMARY OF BACKGROUND DATA: Exposure to diagnostic radiation in patients with adolescent idiopathic scoliosis may result in a small but significant increase in cancer rates. The full-spine radiographic examination remains the standard procedure for the assessment of scoliosis. There is a need for a valid and reliable noinvasive test to assess scoliosis. METHODS: Two examiners independently assessed 105 patients presenting to a scoliosis clinic for trunk asymmetry with Adam's forward bend test and axial trunk rotation with the Scoliometer. The Cobb method served as the gold standard. RESULTS: The interexaminer agreement for the Scoliometer is excellent in the thoracic spine and substantial in the lumbar spine. The interexaminer measurement error shows poor precision for thoracic and lumbar Scoliometer measurements. The interexaminer agreement for Adam's forward bend test is substantial in the thoracic spine and poor in the lumbar spine. Adam's forward bend test is more sensitive than the Scoliometer in detecting thoracic curves measuring 20 degrees or more by the Cobb method. Receiver operating characteristic curve analysis suggests that the use of the Scoliometer marginally improves the ability of diagnosing a scoliosis in the thoracic spine. CONCLUSIONS: The Scoliometer and Adam's forward bend tests have adequate interexaminer reliability for the assessment of thoracic curves. The Scoliometer has better interexaminer agreement in the lumbar spine. However, the Scoliometer has a high level of interexaminer measurement error that limits its use as an outcome instrument. Because Adam's forward bend test is more sensitive than the Scoliometer, the authors believe that it remains the best noninvasive clinical test to evaluate scoliosis.     

Anti-laminin reactivity and glomerular immune deposition by in vitro recombinant antibodies

Growing evidence suggests that recombinatorial events prior to antigen contact can generate pathogenic autoantibodies in the nonautoimmune individual, thus providing potential disease mediators if conditions arise that permit bypass of tolerance and activation of autoreactive lymphocytes. To examine the disease potential of selected germline antibody genes, Ig were created de novo by in vitro recombination of Ig H and L chains. H chain loss variant (i.e., L-chain only) cell lines were transfected with a DNA construct encoding the variable region and regulatory sequences (LamH) of a nephrotropic murine lupus anti-laminin Ig, and the resultant Ig were examined for in vitro antigen reactivity and in vivo glomerular immune deposition. The results indicate that two light chains, LamL (Vk8, Jk5) and 238L (Vk4, Jk5), expressing unrelated germline V1 genes, combine with LamH to generate Ig that bind basement membrane laminin in vitro, diverge in their capacity to bind ssDNA, and produce two distinct patterns of glomerular immune deposits in vivo: dense mesangial matrix (LamH/LamL) and dramatic linear glomerular basement membrane (LamH/238L) deposits. The Ig genes used by both LamH and 238L are present in nonautoimmune mice as well as in lupus-prone strains. We conclude that certain unmutated Ig genes can contribute to multiple distinct disease associated specificities, including binding to intrinsic kidney antigens, and that mutation is not essential to generate these Ig. Collectively, these observations suggest that pathogenic autoantibodies can be generated in the normal preimmune repertoire by random recombinatorial and somatic events in the absence of mutation.     

The role of a single N-linked glycosylation site for a functional epitope of herpes simplex virus type 1 envelope glycoprotein gC

High altitude (HA) living produces physiological changes for adaptation to chronic hypobaric-hypoxemic conditions. Although much is known about these physiologic adaptations, no clear separation has been made regarding what is "native" or "genetic" adaptation and what is "acquired." In this review, we describe the genetic vs. acquired adaptation and only include studies performed in a population native to HA and not in an acclimatized population or trekkers. The changes encountered in animals and humans living at HA in terms of hematology, muscular, respiratory, cerebral, cardiovascular, hormonal, fluid and electrolytes and reproduction, strongly suggest that genetics play a very important role in HA adaptation. Unfortunately, the characteristic physiology of HA natives has not been systematically defined to established specific measurable parameters of adaptation in comparison to the acquired ambient adaptation of the non-native population. Once the parameters are established, we can compare non-native populations exposed to HA that must emulate the HA physiology for a definite adaptation to be present. With measurable parameters, especially in the management of fluids and electrolytes, we can define how long it will take for a sea level native to adapt to an HA altitude. Until these studies are performed, speculation will continue and no rational medical intervention can be offered to HA newcomers who may experience HA difficulties.