Search PubMed⌕ Search

Biomedical subjects

J Walter

Publications and source records attributed to J Walter.

At least 217 records · Page 12Linked to original sources
PubMed1987

Bacterial peptidoglycans as modulators of sleep. I. Anhydro forms of muramyl peptides enhance somnogenic potency.

Chemically defined muramyl peptides (MPs), derived primarily from enzymatic digests of Neisseria gonorrhoeae peptidoglycan, were used to define the structural determinants of MP-mediated somnogenic activity. One of these, i.e. N-acetylglucosaminyl-N-acetyl-1,6-anhydro-N-acetylmuramyl-alanyl-glutamy l- diaminopimelyl-alanine, was structurally identical to the major naturally occurring MP previously detected in mammalian brain and urine. The somnogenic potency of this MP was similar to that of the corresponding disaccharide pentapeptide containing an additional alanine at the C-terminus and the analogous anhydro-muramic acid-containing monosaccharide tetrapeptide lacking the glucosamine moiety. Infusion of as little as 1 pmol of these highly active MPs increased significantly the percentage of slow-wave sleep in experimental animals. In fact, each of 5 anhydro-muramyl disaccharide peptides tested was somnogenic at a dose of 10 pmol or less and, as far as tested, the activity was affected only slightly by the length or composition of the peptide side chain. However, none of a matched set of analogous MPs, differing only in replacement of the anhydro-muramyl end by a hydrated muramic acid residue, was somnogenic at this dose. A modified form of the hydrated muramyl tripeptide containing a free amide on the diaminopimelic acid residue was completely inactive in amounts up to 1000 pmol. Together, the current data suggested: that the anhydro-muramic acid end (but not the glucosamine moiety) is essential for maximal somnogenic potency; and that amidation of carboxyl groups on the peptide-side chain may block MP-mediated somnogenic activity.

Anhydrides↗
PubMed1987

Bacterial peptidoglycans as modulators of sleep. II. Effects of muramyl peptides on the structure of rabbit sleep.

Sleep-promoting substances derived from human urine and rabbit brain were identified as muramyl peptides (MPs). We report in the accompanying paper that in the molecular structure of MPs, the 1,6-anhydro muramic acid moiety of MPs is important for enhancement of slow-wave sleep (SWS) in rabbits. Here, we document more extensively the effects of one MP: 1,6-anhydro-muramyl-alanyl-glutamyl-diaminopimelyl-alanine (AMTP for anhydro-muramyl tetrapeptide) on sleep structure of rabbits. AMTP significantly increased percent of time spent in SWS but its effects on rapid eye movement (REM) sleep were dose-dependent. Brain temperatures were significantly elevated but continued to fluctuate with sleep and wake state transitions indistinguishably from control. Sleep was episodic and animals could be easily aroused. AMTP increased number of SWS episodes and decreased number of REM episodes. There was a shift in the distribution of sleep-wake episode durations: longer waking and REM episodes were decreased, thus increased the proportion of shorter episodes. Increased duration of SWS resulted from a larger number of SWS episodes longer than 8 min. We conclude that AMTP amplifies the SWS compenent of physiological sleep.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Interferon alpha-2 enhances slow-wave sleep in rabbits.

Interferon alpha-2 (IFN) is a leukocyte product with several biological properties including antiviral activity, pyrogenicity and enhancement of immune functions. We report here that an additional facet of IFN activity is its ability to enhance slow-wave sleep (SWS) without greatly altering other aspects of sleep. Intravenous or cerebral intraventricular injections of human IFN into rabbits induced enhancement of SWS, electroencephalographic slow-wave (0.5-4 Hz) activity and brain temperatures. IFN induced slight reductions in rapid-eye movement sleep. Animal behavior, brain temperature changes that occur during the transition from one arousal state to another, and the cyclic nature of states of vigilance remained undisturbed after IFN treatment. The sleep-promoting activity of IFN may be related to feelings of lassitude and sleepiness that often accompany viral disease and interferon therapy. That IFN and other immunoactive substances, e.g. interleukin-1 and muramyl peptides, can enhance sleep suggests that sleep is linked into the immune response.

Animals↗
PubMed1987

Evidence for individuality of breathing patterns in resting healthy man.

This study attempts to answer the question of whether there is a characteristic individuality of breathing pattern in conscious man. Measurements of breathing pattern, electroencephalograms and electrooculograms were made on 41 healthy individuals under standardised conditions of relaxed wakefulness, with a minimum of visual, auditory, and tactile input. Noninvasive measurement techniques were utilised and the subjects did not know that their breathing was being monitored. Measurement periods of only 5 min were used in order to avoid sleep. To estimate reproducibility, subjects were studied four times over two days. A variety of statistical tests on respiratory and cardiovascular variables indicate that the differences between individuals are highly significantly greater than the differences within an individual on repeated measurements under these standardised conditions. There was a high degree of reproducibility of breathing pattern within a subject; respiratory frequency was the most reproducible variable.

Adult↗
PubMed1987

The effect of visual and auditory stimuli upon resting ventilation in man.

We have quantified the effect of visual, and auditory stimulation upon the breathing pattern in resting healthy man. Only noninvasive instrumentation was used. For the visual experiment we studied 36 subjects in each of three conditions: relaxed wakefulness with eyes closed (EC); with eyes open and directed at a white screen (EO); and whilst reading a standardised text (R). For the auditory experiment we studied 18 subjects under three analogous situations: no auditory input (N); listening to white noise (W); and listening to a story (V). In each study, all subjects underwent four replications (over two days) of one of the six permutations of the three experimental conditions; each condition lasted 5 min. A balanced analysis of variance on 10,368 breaths showed that, from baseline EC, both EO and R significantly increased respiratory frequency and ventilation by approximately 6%. Using 5184 breaths in the auditory study the analysis showed qualitatively similar results between analogous situations. The results demonstrate the importance of defining the conditions under which resting VI is measured.

Acoustic Stimulation↗
PubMed1987

Recognition of position-specific properties of tectal cell membranes by retinal axons in vitro.

In order to test the preference of growing axons for membrane-associated positional specificity a new in vitro assay was developed. In this assay, membrane fragments of two different sources are arranged as a carpet of very narrow alternating strips. Axons growing on such striped carpets are simultaneously confronted with the two substrates at the stripe borders. If there is a preference of axons for one or the other substrate they become oriented by the stripes and grow within the lanes of the preferred substrate. Such preferential growth could, in principle, be due to affinity to attractive factors on the preferred stripes or avoidance of repulsive factors on the alternate stripes. This assay system was used to investigate growth of chick retinal axons on tectal membranes. Tissue strips cut from various areas of the retina were explanted and the extending axons were confronted with stripes of cell membranes from various areas within the optic tectum. Tectal cell membranes prove to be an excellent substrate for the growth of retinal axons. Nasal and temporal axons can grow well on membranes of both posterior and anterior tectal cells. If, however, temporal axons are given a choice and encounter the border between anterior and posterior membranes they show a marked preference for growth on membranes of the anterior tectum, their natural target area. Nasal axons do not show a preference in this assay system. The transition from nasal to temporal properties within the retina is abrupt. In contrast, the transition from anterior to posterior properties of the tectal cell membranes occurs as a smooth gradient. Significantly, the positional differences of tectal membrane properties are only seen during the period of development of the retinotectal projection and are independent of tectal innervation by retinal axons. These anterior-posterior differences disappear by embryonic day 14.

Animals↗
PubMed1987

Avoidance of posterior tectal membranes by temporal retinal axons.

Membrane carpets consisting of alternating membrane stripes were prepared from plasma membranes of anterior and posterior chick optic tectum. Axons from retinal explants extend neurites on these carpets. Axons of the nasal retina do not distinguish between the stripes. Axons of the temporal retina prefer to extend neurites on anterior tectal membranes. Treatment of the membrane fragments with high temperature interferes with the pattern of neurite outgrowth from temporal axons. When growing on carpets consisting of treated anterior and posterior tectal membranes, temporal retinal axons no longer distinguish between the stripes. Treatment of posterior membranes alone is sufficient to abolish the preference of temporal axons to extend neurites on anterior tectal membranes. Treatment of the anterior membranes alone has no effect. This result is best explained by a repulsive component in the posterior tectal membranes. Temporal, but not nasal, axons specifically recognize and avoid that component, with the result that they do not extend neurites on posterior tectal membrane stripes. Once the repulsive component is destroyed, temporal axons are able to extend neurites on posterior tectal membranes.

Animals↗
PubMed1987

[Cardiac arrhythmias in active elderly persons--age dependence of heart rate and arrhythmias].

Arrhythmias and heart rate of 82 active elderly persons (mean age 79.5 yrs) were registered by 24-hour electrocardiographic recording and compared with the results of 100 asymptomatic subjects (age 34.8 yrs). In each decade 10 men and 10 women were included. Maximal heart rate was lower in old age but over 100 bpm. Minimal and nocturnal heart rates showed a steady rise with increasing age. The mean 24-hour heart rate was higher in middle-aged females than in males, whereas in the elderly no sex-related difference was observed. Sinus arrhythmia, wandering pacemaker, short lengthening of RR-intervals prevailed in younger persons. Short sinus-tachycardias in the late night were equally frequent in both groups. The frequency of supraventricular premature beats did not differ between the two groups (85.4 vs. 76%). However, high intraindividual numbers and more complex forms were more frequent in the elderly. Paroxysmal atrial fibrillation was never registered. Permanent atrial fibrillation occurred in 41% of the subjects being between 90 and 102 years of age. Ventricular arrhythmias were age-related: 87.2% of the elderly vs. 50% of the middle-age subjects had ventricular premature beats, predominantly frequent and complex forms. A significant age relation to bradycardias could not be observed: Sinus pauses over 2000 ms (11 vs. 17%), first and second degree AV-block (22 vs. 21%) occurred equally frequent in both groups. An intermittent short third degree AV-block was observed in a man 84 years old who was asymptomatic. Right bundle branch block was present only in the elderly (6.1%). No arrhythmia-related increase of mortality was observed during a seven-year follow-up.

Aged↗
PubMed1987

Regrowth, tumor cell proliferation and morphological alterations of the adenocarcinoma EO 771 following a single dose of 30 Gy 60Co gamma-rays.

The effect of irradiation with 30 Gy 60Co gamma-rays on the adenocarcinoma EO 771 has been studied by simultaneously evaluating the effect on tumor growth, on tumor cell proliferation and on the histological structure of the tumor. Inspite of a drastic decrease of tumor cell density by a factor of 2 within one day after irradiation there is practically no tumor regression but only a growth delay lasting about five to six days. The lack of decrease in tumor volume is due to hemorrhages and interstitial oedemas. Regrowth of the tumor starting after about five days concomitantly with the removal of necrotic tissue is followed by a second wave of growth delay. Following the release of the G2 block of the cells tumor cell proliferation is reduced to about half the normal proliferative activity for further three days. Tumor cell proliferation reaches its maximum about eight days after irradiation and then decreases again although higher proliferative activity should be expected comparing the size of the tumor with that in untreated animals. The proliferative activity is much higher in the tumor periphery than in the center suggesting that radiation damage is more rapidly compensated in the tumor periphery. These studies confirm that tumor volume changes are not representative for radiation effects but that there are many processes as damage to the vascular system or the tumor bed effect that influence the effect of irradiation on the tumor.

Adenocarcinoma↗
PubMed1986

Brain temperature changes coupled to sleep states persist during interleukin 1-enhanced sleep.

The effects of human interleukin 1 (IL 1) on the architecture of rabbit sleep-wake cycles and brain temperature (Tbr) changes coupled to states of vigilance were examined. Cerebral intraventricular infusion of IL 1 induced increased slow-wave sleep (SWS), increased electroencephalographic slow-wave (0.5-4 Hz) amplitudes, and fever. Heat-inactivated IL 1 failed to elicit these responses. IL 1 also significantly inhibited rapid-eye-movement (REM) sleep; however, inactivated IL 1 also reduced REM sleep; thus some of the IL 1-induced REM reduction may be related to the infusion process. The duration and number of sleep cycles (REM-to-REM interval) were unaffected by IL 1. Similarly, Tbr changes that normally occur during the transition from one arousal state to another remained unchanged after IL 1 infusion, even though rabbits were simultaneously febrile. We conclude that IL 1 selectively enhances SWS while leaving sleep cycles and Tbr changes coupled to states of vigilance undisturbed.

Animals↗
PubMed1986

Phase I clinical trial of an MAF-containing lymphoblastoid cell line supernatant.

A preliminary Phase I evaluation of macrophage activating factor (MAF) derived from the partially purified supernatant of human RPMI-1788 lymphoblastoid cell line was performed in 4 parts in 39 patients with advanced cancer. The first two parts used subcutaneous routes of administration and the second two parts used a 4-h intravenous infusion method. Individual doses ranged from 0.1 ml (1.7 mg protein) to 100 ml (1,700 mg protein). Subcutaneous dose was limited by the volume of administered material, and an attempt to use a concentrate of the supernatant resulted in severe local skin reactions. Larger doses given intravenously were well tolerated. Resultant toxicity was mild and consisted of transient fever and chills. One patient with malignant melanoma had a complete response of a 3-cm skin metastasis; one patient with breast cancer had disappearance of a skin nodule while visceral disease progressed; and one patient with histiocytic lymphoma had resolution of a conjunctival lesion. Treatment in many patients was associated with an increase in absolute peripheral lymphocytes. In the high-dose intravenous group, a statistically significant increase in the phagocytic index of peripheral blood leukocytes was noted. Lymphoblastoid MAF appears to be relatively safe to administer and has promise both as an antitumor agent and in the treatment of other altered immune conditions.

Adolescent↗
PubMed1986

Obesity induced by kainic acid microlesion in the ventromedial hypothalamus in rats.

The neurotoxin kainic acid was injected bilaterally into the ventromedial hypothalamus of female rats in doses of 100 or 200 ng. The injections produced microlesions which led to progressive body weight gain and fat deposition in dose dependent manner. The histological examination revealed that the lesions were mainly located in the region between the ventromedial hypothalamic nuclei and the fornix.

Animals↗