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Biomedical subjects

B Benz

Publications and source records attributed to B Benz.

16 recordsLinked to original sources

beta-Adrenergic stimulation promotes homocysteic acid release from astrocyte cultures: evidence for a role of astrocytes in the modulation of synaptic transmission.

The sulfur-containing amino acid homocysteic acid (HCA) is present in and released from nervous tissue, exerting excitatory effects on neurons by predominantly activating NMDA receptors. It is interesting that HCA appears to be exclusively localized in glial cells, not in neurons. This profile of glial localization and excitatory action on neurons has led to the hypothesis that HCA could participate in intercellular communication in the brain as a "gliotransmitter." To test this hypothesis further, we searched for specific, receptor-mediated stimuli that could induce release of HCA from cultured astrocytes. For this reason we tested the effect of noradrenaline and vasoactive intestinal peptide, two transmitters known to interact with specific receptors on astrocytes, on the release of HCA from these cells. Noradrenaline and the beta-adrenergic agonist isoproterenol induced an efflux of HCA from astrocyte cultures. Further stressing the beta-adrenergic mediation of this effect is the blockade by atenolol of the HCA release evoked by isoproterenol. The stimulation of HCA release from astrocytes was not observed with the alpha-noradrenergic agonist methoxamine and with vasoactive intestinal peptide. These results taken together further strengthen the role of HCA as a gliotransmitter. Its efflux from glia could be controlled by noradrenaline, activating beta-adrenergic receptors on astrocytes. The present study provides the first evidence for an influence of beta-adrenergic receptor activation on the release of an excitatory amino acid from astrocytes and further supports the notion that glial-neuronal interactions play a role in synaptic transmission.

Adrenergic alpha-Agonists↗

Glutamate-induced release of the nitric oxide precursor, arginine, from glial cells.

Arginine, the nitric oxide precursor, is predominantly localized in glial cells, whereas the constitutive nitric oxide synthase is mainly found in neurons. Therefore, a transfer of arginine from glial cells to neurons is needed to replenish the neuronal precursor pool. This is further supported by the finding that arginine is released upon selective pathway stimulation both in vitro and in vivo. We investigated the mechanism underlying this glial-neuronal interaction by analysing the effect of glutamate receptor agonists on the extracellular [3H]arginine level in cerebellar and cortical slices and in cultures of either cortical astroglial cells or neurons. We present data indicating that arginine is released from cerebellar and cortical slices and astroglial cell cultures upon activation of ionotropic non-NMDA glutamate receptors. Glutamate had no effect on the extracellular [3H]arginine level in neuronal cultures. Moreover, the effect of glutamate in cerebellar slices was tetrodotoxin-insensitive, and the calcium ionophore A23187 evoked the release of [3H]arginine from astroglial cell cultures. Thus, nitric oxide synthesis and nitric oxide transmission may be based on the glial-neuronal transfer of arginine which is induced by activation of excitatory amino acid receptors on glial cells.

Animals↗

Nitric oxide precursor arginine and S-nitrosoglutathione in synaptic and glial function.

In the last few years, there has been an important increase in interest in nitric oxide (NO) as an intercellular messenger, and its putative role in numerous CNS functions is being continually updated. Arginine, the nitric oxide precursor, has been found in our laboratory to be released following stimulation of the white matter in the cerebellum and of sensory afferents in the thalamus. Since arginine is localized in glial cells while the nitric oxide synthesizing enzyme is localized in different cells (predominantly in neurons), these findings may represent a transfer of arginine from glia to neurons in order to supply the nitric oxide synthase with its substrate. The mechanism underlying this glial-neuronal interaction seems to involve the activation of excitatory amino acid receptors present on glial cells. Our results speak for an intense crosstalk between neurons and glia (activation of glial receptors by neurotransmitter released from neurons) and between glia and neurons (supply of the nitric precursor arginine from glia to neurons). The form in which NO is released from cells has been much debated. The chemical identity of the endothelial-derived relaxing factor in particular is still a matter of dispute, the major contender being NO. and a S-nitrosothiol compound. Based on the strong reactivity of NO for thiols and on the presence of cysteine and glutathione at the mM level intracellularly and microM level extracellularly, we have investigated whether S-nitrosothiols, i.e. S-nitrosoglutathione, may be the potential "package" form in which NO could be stored. We demonstrated, with HPLC coupled to mass spectrometry techniques, the presence of endogenous nitrosoglutathione in rat brain tissue. This packaging of NO in the form of nitrosothiols might serve to facilitate its transfer, prolong its life, and target its delivery to specific effectors. That could confer a specificity of action to the widely diffusable messenger NO, may determine the range of effectiveness of NO and mitigate its adverse cytotoxic effects.

Animals↗

DNA replication specificity of TYLCV geminivirus is mediated by the amino-terminal 116 amino acids of the Rep protein.

Geminiviruses are plant DNA viruses replicating by a rolling circle mechanism. We have investigated the specificity of replication origin recognition of two different isolates of tomato yellow leaf curl virus (TYLCV). Here, we show that TYLCV-Sardinian and -Israeli replication proteins display a high degree of specificity for their respective origins. The DNA sequences recognized are located on the left part of the intergenic region whereas the amino-terminal 116 amino acids of the Rep protein determine the specificity of origin recognition.

Bacterial Proteins↗

Effects of verapamil enantiomers and major metabolites on the cytotoxicity of vincristine and daunomycin in human lymphoma cell lines.

Verapamil, a calcium channel blocker, is used as the racemate. Recently, racemic verapamil has been shown to increase the cytotoxicity of vinca alkaloid and anthracycline derivatives in several resistant tumour cell lines. With respect to its cardiovascular activity S-verapamil is an order of magnitude more potent than R-verapamil. Since it was not known whether the effect on multi-drug resistance was also enantioselective a comparison has been made of the potency of the R and S enantiomers and racemic verapamil in their ability to increase the cytotoxicity of vincristine and daunomycin in sensitive (MOLT 4B) and drug resistant human T-lymphoma cell lines (MOLT/VCR-5 x 9, MOLT/DAU-8 and VCR 1000, a highly resistant subline of CCRF-CEM). Two major metabolites, norverapamil and D617 were tested in the same system. (+)-R, (-)-S-, racemic verapamil, norverapamil and D617 alone had no effect on cell growth in sensitive or resistant cell lines in concentrations up to 20 microM. In combination with vincristine, verapamil and norverapamil but not D617 produced a concentration dependent increase in the sensitivity of the resistant lines. Racemic verapamil, its individual enantiomers and norverapamil were equipotent. The concentration of the modifiers required to elicit 50% of the maximum effect (EC50) was of the order of 0.5 microM. No significant difference in the slopes of the concentration-effect curves were observed. The effect of verapamil and norverapamil was additive. In the sensitive MOLT 4B cell line both enantiomers and norverapamil increased sensitivity towards vincristine. However, the EC50 values were at least an order of magnitude higher (2.5-8 microM) than in the resistant cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Daunorubicin↗

[A new instrument for dilatation of esophageal stenoses].

A new system for dilatation of the esophagus is presented. It combines the advantages of both the conventional semi-rigid dilator and the newer balloon method. The variable length of the new balloon provides more strength and a smoother surface. The device is easy to handle, even by the patient himself.

Catheterization↗

Effect of protein synthesis inhibitors and metabolic blockers on the production of placental proteins by the in vitro perfused human placenta.

The capacity of the freshly delivered human term placenta to produce and release placental proteins during in vitro dual perfusion was investigated. The organ was perfused in separate closed circulations and aliquots of medium were taken at regular intervals from both maternal and fetal circuits. The placental proteins human chorionic gonadotrophin (HCG), human placental lactogen (HPL), pregnancy-specific beta 1-glycoprotein (SP1), and pregnancy-associated plasma protein A (PAPP-A) were quantified in these media as well as in the placental tissue before and after the perfusion. It was found that the four above-mentioned proteins were synthesised during the perfusion interval (90 min to 3 h) while pregnancy-associated alpha 2-glycoprotein and prolactin were only washed out. The mean production of HCG, HPL, SP1, and PAPP-A was decreased when either cycloheximide, puromycin, iodoacetic acid, or 2,4-dinitrophenol had been added to the perfusing medium. Amongst these four antimetabolites iodoacetic acid most severely affected both the total release and net synthesis. It is concluded that the above four proteins are synthesised de novo by the perfused placenta in the absence of maternal tissue and that this synthesis is energy-dependent.

2,4-Dinitrophenol↗

The Hitselberger sign as a perception phenomenon.

In the Hitselberger test the patient has to estimate the magnitude of the tactile part of a compound audio-tactile stimulus. From this point of view it is doubtful, that the sign is a simple peripheral phenomenon based on the impairment of the facial nerve by tumor pressure. To investigate the process of audiotactile perception we developed a device which delivers a calibrated compound audio-tactile stimulus. In the tested 70 patients with different sensorineural lesions there was no significant difference between the percentage values of positive Hitselberger signs in the various diagnostic groups. Evaluation of the different factors influencing the Hitselberger test results in a new concept of audiotactile perception.

Acoustic Stimulation↗

A rubella outbreak among dental students: description of the outbreak and analysis of control measures.

From February to April 1982, rubella was diagnosed in 17 Washington University dental students. The affected students represented 4.8% of all dental students and 21% of susceptible students. Because a high likelihood of rubella transmission was perceived, three adjacent university hospitals undertook an emergency program to ensure immunity to rubella in all personnel. The program reached 84.6% of all target personnel, but only 36% of physicians (p less than 0.001). We estimated that the program increased the level of rubella immunity from 92.2% to 98.1%, at a total cost of $140,274 of which $29,990 was in excess of ordinary expenditures. Our experience indicates that schools training health professionals face the possibility of rubella outbreaks unless they ensure rubella immunity in all students. The experience also supports the value of ongoing programs to ensure rubella immunity in hospital personnel. Without such programs, hospitals may be forced to undertake emergency programs that are likely to be disruptive and expensive and may have relatively little immediate measurable impact.

Antibodies, Viral↗

Prevalence of hepatitis B antibodies in personnel at a children's hospital.

Antibody to hepatitis B core antigen and antibody to hepatitis B surface antigen were measured in serum samples from 825 personnel at St Louis Children's Hospital (702 were possibly at high risk of occupational hepatitis B virus (HBV) exposure and 123 were office personnel); 5.6% had positive findings for both antibodies, 5.6% had findings for antibody to hepatitis B surface antigens alone, and 1.3% had positive findings for antibody to hepatitis B core antigens alone. The group with positive findings for antibody to hepatitis B surface antigens alone did not have traditional risk factors for HBV infection, suggesting that this serologic finding may not be a reliable indicator of past HBV infection. After accounting for the effects of age, sex, and ethnicity, it was found that no occupational group had a significantly increased prevalence of HBV antibodies compared with prevalence in other personnel. In comparison with volunteer blood donors, only physicians older than 40 years of age had an increased HBV antibody prevalence. It is concluded that St Louis Children's Hospital has not been a high-risk environment for HBV exposure in recent years. However, caution is advised in generalizing these conclusions because other children's hospitals may serve a patient population at higher risk of HBV infection. Decisions regarding HBV immunization policy should take into consideration the fact that personnel at different hospitals may face markedly different risks of HBV exposure.

Adult↗

A mydriatic eye-drop combination without systemic effects for premature infants: a prospective double-blind study.

Eye drops used for diagnostic mydriasis may produce systemic side effects in preterm infants. Studies on the pupil dilating and systemic effect of various mydriatic agents yielded conflicting results. We conducted a prospective randomized double-blind study on the systemic effect of two mydriatic eye-drop combinations. Thirty-nine preterm infants were randomly assigned to two groups. An eye-drop combination of 2.5% phenylephrine and 0.5% tropicamide (group D) was compared with the combination of 0.5% cyclopentolate and 0.5% tropicamide (group F). Either eye-drop combination was followed by 0.5% tropicamide given 20 minutes later. Heart rate (HR) and the systolic, mean, and diastolic blood pressure (BP) were recorded before and after eye-drop instillation and after ophthalmoscopy. A control session with NaCl eye drops was added for each infant. A significant increase of BP and HR peak values was observed within 7 to 10 minutes after the cyclopentolate/tropicamide combination only. On the other hand, the mydriatic effect of the phenylephrine/tropicamide combination was significantly superior to that of the cyclopentolate/tropicamide combination. We recommend the combination of 2.5% phenylephrine and 0.5% tropicamide to achieve a sufficient diagnostic mydriasis without systemic side effects in preterm infants.

Blood Pressure↗