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At least 109 records · Page 6Linked to original sources
PubMed1979

Forward masking of auditory nerve fiber responses.

1. Responses of single fibers were obtained from the auditory nerve of chinchillas. Tone-burst stimuli consisted of a masking stimulus followed by a probe stimulus. Forward masking of a fiber's response is defined as a reduction in the magnitude of the probe-evoked response caused by the addition of the masking stimulus. 2. The recovery of probe response magnitude as a function of the time interval between masker offset and probe onset (delta T) follows an exponential time course. A relationship between the time course or magnitude of poststimulus recovery and the characteristic frequency (CF) of a fiber was not detected. 3. The iso-forward masking contour near the threshold of the masking effect across masker frequencies approximates a fiber's frequency threshold curve (FTC). In other words, forward masking tuning curves are essentially the same as frequency threshold curves. 4. The frequency dependence of forward masking is compared to that of two-tone suppression. Tonal stimuli outside the boundaries of a fiber's FTC that produce two-tone suppression are ineffective forward maskers. Certain frequency/intensity combinations within the FTC may produce both suppression and forward masking and tones within the remaining area of the FTC produce no suppression but are effective forward maskers. 5. Both the time course and the magnitude of the forward masking effect are dependent on the discharge rate evoked by the masker regardless of the masker's absolute level or spectral content. An increase in masker-evoked excitation causes an increase in time constant and a greater reduction in probe response magnitude, rd. The function relating rd to masker level parallels the firing rate/masker level function up to 40 dB above response threshold. 6. A decrease in masker duration from 100 ms leads to a decrease in both rd and the time constant of recovery. There is no significant difference between the 100 and 200 ms duration conditions. 7. Forward masking in single fibers is related to the period of poststimulus recovery of spontaneous activity, a component of a fiber's response pattern to the masker, and this component is tentatively identified as a period of recovery from short-term adaptation.

Adaptation, Physiological↗
PubMed1976

Light-induced enzyme synthesis in cell suspension cultures of Petroselinum hortense. Demonstration in a heterologous cell-free system of rapid changes in the rate of phenylalanine ammonia-lyase synthesis.

The conditions for protein synthesis in vitro with polyribosomes from cell suspension cultures of parsel (Petroselinum hortense) and a wheat-germ extract were investigated. Two different criteria were used as estimated of the translational activity: (a) the total rate of incorporation of [35S]methionine into acid-insoluble material; (b) the ratio of large (molecular weight greater than 25000) to small (molecular weight less than 25000) peptide products. Depending on which of the criteria was employed, the pH optimum and the optimal concentrations for Tris=acetate, magnesium acetate, KCL, methionine and the wheat-germ extract differed considerably. The translational activity of the polyribosomes (both criteria) was effciently protected by 0.1 M Mg2+ against degradation during the isolation procedure. The rate of synthesis of phenylalanine ammonia-lyase in vitro with the polyribosomes was determined by measuring the incorporation rate of L-[35S]methionine into protein which was precipitable by a rabbit antiserum prepared for the purified enzyme. The immunoprecipitate was analyzed by disc gel electrophoresis in the presence of dodecylsulfate and was shown to contain small amounts of the complete enzyme subunits and relatively large amounts of shorter peptides which were also characteristic for the enzyme. The time course of light-induced changes in the rate of phenylalanine ammonia-lyase synthesis in vitro were investigated during a period of 15 h under two different conditions of induction: the cell cultures were irradiated with ultraviolet light eith (A) continuously or (B) for 2.5 h and then returned to darkness. Although the highest rate of enzyme synthesis was observed somewhat later inexperiment A than in experiment B, the periods of time during which the rate of synthesis increased rapidly were limited in both cases to only a few hours. The results obtained in vitro were identical within the limits of the experimental error with theoretical calculations of the changes in the rate constant of phenylalanine ammonia-lyase synthesis in vivo. These changes were calculated from the corresponding curves for the changes in the enzyme activity under the conditions of induction. The results are in agreement with previous observations suggesting that the induction of phenylalanine ammonia-lyase by light in the parsley cells was a short-term effect whose efficiency was greatly reduced within the 15 h of experimentation, even under continuous irradiation.

Ammonia-Lyases↗
PubMed1975

Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity.

Fenfluramine has been used for a number of years as a short-term adjunct to diet in the management of obesity. Controlled studies and clinical experience have shown that it possesses anorectic activity at least as good as that of other therapeutically useful drugs of its type, but like these drugs it has only a limited role in the overall management of obesity. Tolerance to the anorectic effects of fenfluramine may possibly develop more slowly than to other chemically related drugs in patients with refractory obesity. The mechanism of its anorectic action is probably by an effect on the appetite control centres in the hypothalamus, rather than by an effect on glucose and lipid metabolism. However, its effect in enhancing glucose uptake into skeletal muscle may be of advantage in diabetes mellitus, preliminary studies suggesting that it is of potential use in maturity-onset obese diabetics who cannot be adequately controlled by dietary measures alone. The starting dosage in obesity of 40mg daily should be increased gradually over 2 to 4 weeks to 60 to 120mg. In general, little extra benefit is gained by higher dosage. When a course of therapy is to be discontinued, fenfluramine dosage should be reduced gradually over a period of 2 to 4 weeks in order to avoid mood depression which has occurred in some patients on abrupt withdrawal of the drug. With these recommendations, the majority of patients tolerate fenfluramine satisfactorily, although some patients may have to discontinue the drug because of troublesome gastro-intestinal problems, diarrhoea, drowsiness or dizziness. Unlike other amphetamine-derived anorectics, fenfluramine is not a central stimulant in therapeutic doses, and it probably has little abuse potential.

Adult↗
PubMed1979

Influence of an intertrial interval on sequential effects related to preparatory period duration for reaction time-task.

In reaction time tasks, where the moment of occurrence of the response signal is uncertain, the temporal constraints of preparatory processes imply that subjects distribute their preparation during the preparatory period. The notion of cost of preparation has been proposed to explain the time course of these processes. This experiment was run to determine the effect of the cost of preparation on a serial-RT task and on a RT task where a rest interval of various possible durations (3, 6, or 9 sec.) is introduced. 12 subjects were tested. Data show that the amount spent on preparation during a trial affects the subject's performance during the next trials. But an hypothesis about memory search must also be advanced to explain the effect of the rest interval on the relationship of RT and the current preparatory period.

Humans↗
PubMed1977

A psychometric evaluation of the acute tremulous state.

The acute alcohol withdrawal state (tremulous state), with mainly vegetative symptoms and without evident loss of conciousness or confusion, was evaluated as to functional psychopathological disturbances aiming to present a complete and objective record of the clinical findings and to establish a control of the course and drug treatment. We tried to meet the inherent inability to cooperate by using proven and also new test devices (flicker fusion, simple reaction time on light and tone, reaction on multiple serial stimuli, visual motor coordination, tachistoscopic perception and memory test, test of concentration and sustained performance with simple arithmetical calculation by analogy with the Pauli test) to circumvent the difficulties arising when patients have to answer long questionnaires. The tests enabled a measurement of the disturbances as objective as possible and proved to have a discriminating sensitivity for different functions. The correlations between the results were found to be similar for alcoholics and controls. tthe degree of the established functional cerebral and cerebellar defects which was revealed was more severe than expected in this mild stage of withdrawal.

Adult↗
PubMed1978

Comparative studies of intracellular transport of secretory proteins.

The physiology of protein intracellular transport and secretion by cell types thought to be free from short-term control has been compared with that of the pancreatic acinar cell, using pulse-chase protocols to follow biosynthetically-labeled secretory products. Data previously obtained (Tartakoff, A.M., and P. Vassalli. J. Exp. Med. 146:1332-1345) has shown that plasma-cell immunoglobulin (Ig) secretion is inhibited by respiratory inhibitors, by partial Na/K equilibration effected by the carboxylic ionophore monensin, and by calcium withdrawal effected by the carboxylic ionophore A 23187 in the presence of ethylene glycol bis (beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and absence of calcium. We report here that both inhibition of respiration and treatment with monensin slow secretion by fibroblasts, and also macrophages and slow intracellular transport (though not discharge per se) by the exocrine pancreatic cells. Attempted calcium withdrawal is inhibitory for fibroblasts but not for macrophages. The elimination of extracellular calcium or addition of 50 mM KCl has no major effect on secretory rate of either fibroblasts or macrophages. Electron microscopic examination of all cell types shows that monensin causes a rapid and impressive dilation of Golgi elements. Combined cell fractionation and autoradiographic studies of the pancreas show that the effect of monensin is exerted at the point of the exit of secretory protein from the Golgi apparatus. Other steps in intracellular transport proceed at normal rates. These observations suggest a common effect of the cytoplasmic Na/K balance at the Golgi level and lead to a model of intracellular transport in which secretory product obligatorily passes through Golgi elements (cisternae?) that are sensitive to monensin. Thus, intracellular transport follows a similar course in both regulated and nonregulated secretory cells up to the level of distal Golgi elements.

Calcimycin↗
PubMed2026

Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia.

The genetic mechanisms underlying heterogeneity in symptom presentation and antipsychotic response in schizophrenia remain unclear, limiting the development of personalized treatment. We integrated genome-wide schizophrenia polygenic risk scores (SZ-PRS) and pathway-specific PRSs (pPRSs) for four major neurotransmitter systems to examine their associations with clinical phenotypes across the course of illness. Primary analyses were conducted in 394 drug-naïve, first-episode patients from the Chinese First-Episode Schizophrenia Trial (CNFEST) to investigate associations with baseline symptom severity, neurocognitive impairment, and longitudinal treatment response. The CNFEST cohort included 52-week longitudinal assessments of symptoms and neurocognition using the Positive and Negative Syndrome Scale and a modified version of the MATRICS Consensus Cognitive Battery. An independent case-control cohort evaluated associations with schizophrenia diagnosis, while a cohort of 514 healthy adults assessed whether PRS-cognition associations are specific to schizophrenia. Higher SZ-PRS predicted schizophrenia diagnosis (OR = 2.28, Pfdr = 0.003) and poorer baseline executive function (β = -0.44, Pfdr = 0.006) and working memory (β = -0.49, Pfdr = 0.018), but these associations were absent in healthy adults. In contrast, pPRSs showed weaker associations with diagnosis and baseline cognition but were more informative for treatment outcomes: higher serotonin-pPRS predicted greater improvement in depressive symptoms (Pfdr = 0.023-0.032), and higher GABA-pPRS predicted greater improvement in overall symptoms (Pfdr = 0.038-0.043) during weeks 4-24. Exploratory drug-specific analyses further suggested that treatment response varied across antipsychotics and was differentially associated with pPRSs. These findings demonstrate that genome-wide and pathway-specific PRSs contribute distinctly to schizophrenia phenotypes, supporting their integration for personalized stratification and treatment.

Humans↗
PubMed1977

Cholinergic mechanisms and short-term potentiation.

Acutely prepared rabbits were used to study, electrophysiologically, tetanic and post-tetanic potentiation of the pathway from the medial septal region to hippocampal field CA1. It was found that tetanic potentiation, evoked by short stimulus trains, was maximal at 6--8 Hz. Responses recovered from post-tetanic potentiation in 5--35 seconds. Acetylcholine, physostigmine, and cyclic GMP each had an excitatory effect on pyramidal cell responses when applied in stratum radiatum. The time course studies showed that these effects outlasted the duration of the injection current by many minutes. Phosphodiesterase inhibitors (e.g., isobutyl methyl xanthine) prolonged the time course of recovery with test responses which were post-tetanically potentiated. K+, on the other hand, selectively enhanced tetanic potentiation. It is suggested, with respect to the potentiation phenomena, that K+ acted primarily presynaptically to facilitate transmitter release, whereas cyclic GMP acted primarily postsynaptically for the enhancement of pyramidal cell excitability.

Acetylcholine↗
PubMed1978

Short-term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system.

The spontaneous activity of neurons in the head of the striatum was studied in rats 3 days and more than 1 year after a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine system in comparison to unlesioned animals. Cells were detected and tracked by stimulating the excitatory corticostriatal pathway. In unlesioned animals striatal cells discharged at very low frequencies, with a median of 0.04 impulse/second. The activity was increased to 0.28 impulses/second 3 days after the lesion. This increase was related to the degree of dopamine depletion. More than 1 year after the lesion, the frequency had decreased to a level indistinguishable from that measured in unlesioned animals, with a median of 0.03 impulses/second. Cells in 3-day lesioned animals discharged a higher number of bursts at shorter intervals as compared to unlesioned animals, while in long-term denervated animals the bursting pattern was similar to that in unlesioned animals. This demonstrates that removal of the dopaminergic input results in increased activity only during an initial phase and that adaptive processes subsequently occur. The data from this Parkinsonian model suggest that symptoms of this disease cannot simply be related to an increased striatal cellular activity. The fact that the initially increased spontaneous activity adapted indicates that functional effects of a lesion can only be evaluated when studying the resulting changes throughout a time course.

Action Potentials↗
PubMed1978

The measurement of change in endogenous affective disorders.

Psychopathological syndromes, as originally revealed by clinical observation, can also be detected by multivariate statistical analyses of symptom ratings. Changes in the course of psychiatric syndromes may be rated simply by improvement scales or by consecutive quantifications of symptoms and their comparison in chronological order. For the latter approach, which is less liable to bias, clinical ratings of psychopathology by staff members, self-ratings by the patients, analyses of patients' overt behavior (including video and speech records), or objective measurements of psychological and/or physiological variables can be used. Advantages and limitations of these different methods are discussed and illustrated by examples from ongoing clinical research in affective disorders. Generally, the combined use of different rating procedures is recommended. Self-ratings are economical, but they may represent aspects of psychopathology other than clinical ratings. In endogenous depression, mood scales are valid (supplementary) tools for the quantification of long-term as well as short-term changes, including diurnal variations. In severe conditions of mania, however, clinical rating has been--until now--the only valid basis for quantifying the degree of psychopathology and its changes with time. Precise evaluation of changes in psychopathology is essential in longitudinal investigations of endogenous affective disorders, since psychopathology up to now seems to have been the most sensitive and the most specific indicator of the hypothetical underlying abnormalities of cerebral functioning.

Affect↗
PubMed1979

Long-term course of chloroquine retinopathy after cessation of medication.

Seven patients with chloroquine retinopathy were examined ten years after their therapy with chloroquine or hydroxychloroquine, or both, had been discontinued and an additional five patients with chloroquine retinopathy were similarly examined from two to eight years after their therapy had been discontinued. Visual acuity, visual fields, and ophthalmoscopic examinations were compared to those performed at the time therapy was discontinued. These long-term observations confirmed the previously published observations based on short-term studies that chloroquine retinopathy tends to remain stable after therapy is discontinued, although a few patients in the early stages of retinopathy may show regression and occasionally a patient with a more advanced stage of the disease may show progression.

Adult↗
PubMed1977

Effect of short-term cyclic administration of cyproterone acetate on pituitary-ovarian function in the human.

Short courses of cyproterone acetate, a compound with progestational and antiandrogenic activities, were administered to normally menstruating women during different phases of the menstrual cycle to suppress growth and maturation of the follicles and corpus luteum function. Postovulatory administration of 20 mg of the drug daily for 8 days to two women delayed menstruation by 4 to 6 days, followed by prolonged bleeding and short post-treatment cycles. Plasma levels of progesterone were suppressed temporarily during therapy, but increased immediately after cessation of treatment. Administration of 10 mg of the drug for 8 days during the early follicular phase to two women resulted in irregular bleeding, short cycles, and decreased plasma levels of progesterone throughout the cycle. Reduction of the dose to 2.5 mg during the early follicular phase in two other women also resulted in irregular cycles. When the 2.5-mg dose was administered to three women from the 8th to the 15th days of the cycle, vaginal bleeding and cycle length were normal. Plasma levels of luteinizing hormone and progesterone were suppressed during therapy. In one subject, cervical mucus was found to be hostile to sperm penetration in all three treatment cycles. The results indicate that, with cyclic administration of low doses of cyproterone acetate to women during the late follicular phase, it may be possible to interrupt pituitary-ovarian function, as well as sperm transport through the cervical mucus.

Body Temperature↗
PubMed2026

Adverse pregnancy outcomes and long-term cardiovascular disease risk.

Pregnancy provides a unique physiological stress test for the cardiovascular system, during which, adverse pregnancy outcomes (APOs) can unmask latent susceptibility to future disease. Common complications, including hypertensive disorders of pregnancy (HDP), gestational diabetes, and preterm birth (delivery before 37 weeks' gestation), identify women at substantially higher long-term risk of cardiovascular morbidity and mortality compared with women without a history of APOs. These excess risks likely reflect the combined effects of pre-existing cardiometabolic and genetic susceptibility, as well as the haemodynamic and metabolic stressors of pregnancy, heralding accelerated risk factor trajectories, relative impairment in endothelial and microvascular function, and early disease onset. This final Review in the Series extends the focus from cardiovascular disease during pregnancy and HDP to the long-term cardiovascular implications of APOs after delivery. We synthesise epidemiological data quantifying cardiovascular risk across major APO phenotypes and emerging evidence linking maternal APO history with cardiometabolic risk trajectories in offspring. We also delineate putative mechanistic pathways and summarise guidelines and consensus-informed recommendations for short-term and long-term follow-up after APOs. Finally, we propose practical approaches for integrating APO history into cardiovascular disease risk assessment and guideline-directed prevention across the female life course. We highlight key knowledge gaps, including uncertainty about optimal follow-up models, the limitations of current risk-stratification tools, and the absence of APO-specific prevention trials. We also outline priorities for mechanistic and implementation research. Positioning APOs as early, sex-specific indicators of cardiovascular risk offers a key window of opportunity to shift prevention upstream and improve cardiovascular health outcomes for women.

Humans↗
PubMed2026

Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.

BACKGROUND & AIMS: Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS: Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS: Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 &#x3bc;g/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS: Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.

Inflammatory bowel disease↗
PubMed1976

Reduplicative paramnesia.

A striking behavioral abnormality is described in three individuals who had severe head trauma. At a point when general mnestic capabilities had returned to a near normal level, the patients persistently relocated the hospital at another geographical site, even in the face of compelling counter-evidence. The strong parallels in the etiology and course of the three cases justify the positing of a syndrome, here termed reduplicative paramnesia. A neuropsychologic analysis of the disorder stresses the cognitive operations entailed in geographical localization and confabulation. Clinical-pathologic considerations underline the role of right hemisphere and frontal lobe structures in the syndrome.

Adult↗
PubMed1976

[Tetanic fatigue and proximate post-tetanic recuperation in sartorius and flexor carpi radialis muscles of the male frog. Effects of iodoacetic acid (author's transl)].

The time-course of the isometric tension output, at 20 degrees C, during a long tetanus and after a short period of rest, was investigated in two isolated frog muscles : the sartorius and flexor carpi radialis muscles. To prevent aerobie and glycolytic recovery processes, some muscles were poisoned with 0,4 mM iodoacetic acid (IAA) and nitrogen, for 20 or 40 min. 1. For the unpoisoned sartorius muscle, tetanic tension declined quickly, but after a 0,8 sec period of rest, the muscle was able to develop high tension. Poisoning with IAA-N2 increased fatigue without suppressing the property of a proximate post-tetanic recuperation. 2. In the flexor carpi radialis muscle resistance to fatigue was very large before poisoning and diminished after poisoning. Proximate recuperation was very weak. 3. The results show that the recovery processes are not a primary factor of the development of the short-term fatigue ; they enhance the hypothesis that a failure of the electromechanical coupling can explain the rate of the tension fall in tetanized sartorius muscles.

Anaerobiosis↗
PubMed1975

[Special pharmacokinetic aspects in newborns and young infants].

The safety of drug therapy in the newborn period and early infancy is endangered for two main reasons: 1. The relative distribution volume of drugs during maturation and in pathological states varies greatly and thus makes conventional dosage in short-term therapy ineffective. 2. During early childhood, the rate of elimination of many drugs is slow hence there is a risk of overdosage in long-term therapy with doses considered safe in older children. The example of two drugs demonstrates, that the course of blood levels is not only dependent on the elimination half life and on the relative distribution volume, but may also be modified to a large extent by the process of invasion. This increases the risk of iron-dextrane but contributes to the safety of Cephalexine. If drug therapy is to be safe and effective in childhood at least the basic elements of a most simple pharmacokinetical model consisting of Invasion, Volume of Distribution and Elimination must be known as can be shown by the mathematical extrapolation of blood level curves gained from single applications for long-therm therapy.

Age Factors↗
PubMed1979

Effect of short-term administration of cyproterone acetate on the reproductive tract histology, ovarian and serum cholesterol contents of female monkey (Presbytis entellus entellus).

Short courses of cyproterone acetate, a compound with progestational and antiandrogenic activities were administered to normally cycling female monkeys to investigate into the effects of cyproterone acetate on the reproductive tract. In little earlier follicular stage 20 mg of the drug daily for 30 days increased the cholesterol contents in the gonads. Serum cholesterol contents were slightly increased. When the reproductive tract was examined histologically, the gonads showed reduction in size, along with widespread degeneration of the young follicles as well as other growing follicles. Uterus showed progestational endometrial proliferation and sloughing of the vaginal productive tract.

Animals↗