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Biomedical subjects

G Mohn

Publications and source records attributed to G Mohn.

At least 19 recordsLinked to original sources
PubMed2000

Application of a dynamic in vitro gastrointestinal tract model to study the availability of food mutagens, using heterocyclic aromatic amines as model compounds.

The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlled in vitro system that mimics the human physiological conditions in the stomach and small intestine. In the current TIM physiological parameters such as pH, temperature, peristaltic movements, secretion of digestion enzymes, bile and pancreatic juices, and absorption of digested products-by removal through dialysis-was simulated. Heterocyclic aromatic amines (HAA; viz. IQ, MeIQ, MeIQx and PhIP) were used as model compounds for food mutagens, and the passage through TIM was investigated for each of these compounds separately. Subsequently, the influence of a matrix and different rates of passage on the availability for absorption and distribution were studied in experiments with prepared meat, supplemented with MeIQx. Samples taken at various time points from the jejunal and ileal dialysates and from the lumen at the end of the small intestine (ileal delivery) were tested for the presence of mutagenic activity in the Ames test with Salmonella typhimurium strain TA98 as indicator, in the presence of mammalian metabolic activation (rat S9 mix). The results show that, comparable with the human in vivo situation, all four HAA are quickly removed (approx. 50% in 2 hr; approx. 95% in 6 hr) and mainly recovered from the lumen into the jejunal and ileal dialysates (94% of recovery). Only 5+/-1.5% is recovered in the chyme at the end of the small intestine. When MeIQx was added to meat, its availability for absorption was slower, although the influence of the gastrointestinal passage time on the availability of MeIQx was more pronounced than this matrix effect. More MeIQx was found in the jejunal dialysate (23%; P<0.01) and less in the ileal delivery (8%; P<0.01) when simulating the gastrointestinal passage of solid meals was compared to simulating that of liquid meals. The present experiments demonstrate that TIM can be applied to study in vitro the availability of heterocyclic aromatic amines in the gastrointestinal tract. More generally, these studies indicate that TIM shows promise as a useful tool for various research purposes dealing with the availability for absorption of mutagenic as well as antimutagenic components in food.

Biological Availability↗
PubMed1994

Solution structure of pyoverdin GM-II.

The three-dimensional structure in solution of ferri-pyoverdin GM-II isolated from the culture medium of Pseudomonas fluorescens was determined by application of NMR methods to the Ga3+ analogue. Distance geometry calculations were performed with FILMAN using interproton distances and coupling constants as constraints. Further conformational analysis was carried out by energy minimization with MM2 and AMBER. Back-calculation of the NOESY spectra shows that the resulting structures are in agreement with the experimental data.

Amino Acid Sequence↗
PubMed1992

The development of vernier acuity in human infants.

Vernier acuity, i.e. the detection of a small misalignment between lines, is about one order of magnitude finer than the resolution of periodic gratings in adult humans. This hyperacuity is generally attributed to cortical mechanisms, and the time-course of its development seems to differ from the development of grating resolution that probably is limited by retinal factors. We investigated 271 human infants and children between 2 months and 8 yr of age with essentially identical stimuli and experimental procedures. Vernier thresholds for Vernier targets were compared to grating resolution. The preferential looking experiments led to the following results: (i) Vernier acuity starts below grating resolution. (ii) Like grating resolution, Vernier acuity develops gradually, but more rapidly and longer; at the age of 5 yr performance becomes comparable to that of adults. (iii) Flanking borders without offset, added to the Vernier targets at various distances, did not affect thresholds consistently across distances and age groups.

Adult↗
PubMed1990

[Monitoring of vision development following early surgery of congenital cataracts using the Acuity-card method].

The recently developed acuity card procedure provides rapid assessment of visual acuity in preverbal infants and thus offers the possibility of monitoring the visual development of infants after early surgery for congenital cataract. This report describes our experience with these acuity cards in seven patients with bilateral and seven patients with unilateral congenital cataract. The age at operation was between 1 week and 17 months; visual acuity was assessed up to an age of maximally 2.5 years. In agreement with previous reports, the development of acuity in infants with unilateral aphakia was better if surgery had occurred within the first 6 months of life than at a later time. The results of acuity assessment were generally in good agreement with the clinical signs. The advantages of the acuity cards in clinical use are that: (1) they provide an additional criterion for surgery, including cases of secondary cataract formation; (2) they allow early assessment of the success of the operation; (3) they can be used to judge occlusion therapy; (4) they have proved to be highly motivating for parents to comply conscientiously with the therapeutic measures. Thus, the acuity card procedure has proved to be extremely useful for the assessment of visual development in infants operated on for congenital cataract.

Cataract↗
PubMed1989

Effects of very low birth weight (VLBW) on visual development during the first year after term.

Behavioural visual functions were assessed in 155 very low birth weight (VLBW) infants during the first 12 months after expected term. Visual development was examined (mainly cross-sectionally) at 6 weeks, 3, 6, 9, and 12 months of corrected age by assessment of visual acuity, visual fields, optokinetic nystagmus and visual threat response. Many VLBW infants showed visual impairments (54.2%). No single visual function appeared to be specifically susceptible to impairments, deficits were often apparent across a range of functions. Visual impairments were observed at all test ages, and could already be assessed at 6 weeks of corrected age. The highest incidence of visual impairments was scored at 6 months corrected age. Beyond 6 months, less deficits were observed, suggesting in many infants a delayed rather than a permanently impaired visual development. In some infants deficits became evident at a later stage, after an apparently normal initial development. The results suggest that VLBW infants are at risk for impaired visual development.

Humans↗
PubMed1989

[Assessment of visual acuity in simulation and aggravation].

Following a review of various tricks and techniques described in the literature for measuring the visual acuity of less cooperative patients, three new methods are presented. The first is based on the so-called "preferential-looking" method, which has been in use for several years to determine the visual acuity of infants and small children. The second method uses polarizing filters to separate the beam paths of the two eyes and a flashlamp to project the test symbols, to prevent the patient from finding out by blinking which eye is being tested. In the third method the stimuli are presented on a computer monitor; the beam paths of the two eyes are separated by special spectacles which can briefly cover either eye while a test symbol is being shown. The results so far are encouraging.

Humans↗
PubMed1989

Assessment of visual function in suspected ocular malingering.

Three new techniques are presented for assessing visual acuity in the presence of suspected malingering. The first technique is based on the preferential looking method commonly used to test acuity in infants. The second uses polarising filters to present stimuli briefly to both eyes or to each eye alone, without the patient's being aware of which eye is tested. The third presents the stimuli on a computer monitor and separates the ray paths of the two eyes by means of special spectacles that obscure vision in one eye for fractions of a second while a stimulus is presented.

Humans↗
PubMed1988

Acuity assessment of non-verbal infants and children: clinical experience with the acuity card procedure.

The acuity card procedure was used to assess the visual acuity of 510 neurologically normal and abnormal infants and children. Acuity estimates were obtained for 93 per cent of 842 binocular and 279 monocular tests. The observed development of binocular acuity of normal fullterm and preterm infants agreed well with previous reports using the traditional forced-choice preferential looking technique. Monocular tests seemed to support earlier suggestions that grating acuity may be relatively insensitive to strabismic amblyopia. Infants at risk of later neurological deficits but developing normally had only a slight delay in development of acuity, but there was a high incidence of acuity deficits (54 per cent) among those with severe neurological defects. The great majority of a group of multiply handicapped children had low acuity for age. Repeat tests showed a high degree of test-retest consistency. The acuity card procedure was a successful and useful method for assessing the acuity of infants and children who cannot be tested with standard ophthalmological methods.

Adolescent↗
PubMed1986

Studies on the metabolic activation of diethanolnitrosamine in animal-mediated and in vitro assays using Escherichia coli K-12 343/113 as an indicator.

The mutagenic activity of diethanolnitrosamine (NDELA), a carcinogenic compound which leads to inconsistent results in standard in vitro procedures was tested in vitro and in animal-mediated assays with the indicator strain Escherichia coli (E. coli) K-12 343/113. This strain allows the simultaneous detection of forward and back mutations arising in several genes of the E. coli chromosome. In animal-mediated assays in which mice were used as hosts for i.v. injected E. coli indicator cells, s.c. application of NDELA induced a dose dependent increase of galactose fermenting mutants in cells recovered from the livers of animals exposed for 3 h to the mutagen. Comparison with results obtained with diethylnitrosamine (DENA) in the same test system revealed that the two compounds apparently cause different types of mutagenic lesions. Induction of arg+ mutations by DENA and several other aliphatic nitrosamines is mainly due to base pair substitutions, whereas NDELA is rather mutagenic in the galRs system. This latter system is, in addition, sensitive to frameshifts and deletions. These differences in mutagenic specificity suggest that NDELA and DENA, although structurally closely related, are activated via different molecular mechanisms. In fact, evidence is accumulating that alcohol dehydrogenase (ADH) could be involved in the activation of NDELA. On the other hand, the effective mutagenesis of NDELA obtained in vitro with E. coli upon addition of rat liver microsomal fraction would not be expected if ADH is involved in the activation since the S-9 Mix used in the present experiments was devoid of cofactors (NAD, NADP), necessary to accomplish oxidation by ADH. Therefore, further in vivo studies were performed, in which pyrazole, a potent blocker of ADH, was administered prior (1 and 24 h) to the injection of the mutagen. The observation that a dose dependent increase of mutants in the liver (and to a lower extent in the spleens) of treated animals takes place under conditions in which ADH activity is blocked, whereas several microsomal enzymes are stimulated, indicated that besides oxidation of NDELA by ADH other metabolic activation pathways are involved. Apparently enzymes contained in the liver homogenate, possibly NADPH dependent enzymes of the microsomal ethanol oxidizing system, play an important role in the formation of mutagenic metabolites of NDELA.

Animals↗
PubMed1986

The development of visual acuity in normal fullterm and preterm infants.

The development of visual acuity during the first year of life was assessed in 91 normal fullterm infants and 36 preterm infants with minimal perinatal complications, using the forced-choice preferential looking technique. Acuity in the preterm infants lagged behind that of the fullterm infants up to the age of 6-8 months if age was calculated from birth, and then reached equal levels. When age was corrected for prematurity, acuities in the two groups were very similar at all ages, but mean preterm acuity was consistently slightly higher than in the fullterm infants. The results suggest that early visual experience of preterm infants in the period up to the expected date of term may lead to a slight acceleration of the development of behavioural visual acuity. This is discussed in relation to electrophysiological studies which report a greater effect of prematurity on acuity development.

Aging↗
PubMed1986

Monocular acuity in normal infants: the acuity card procedure.

An "acuity card" technique has been developed for rapid assessment of visual acuity in infants. In this procedure an adult observer shows the infant a series of cards that contain gratings of various spatial frequencies and estimates acuity as the highest spatial frequency that the infant is judged to see. The present paper shows that the acuity card procedure can be used in a laboratory setting to estimate both monocular and binocular acuity in infants 1 to 12 months of age. Four monocular and two binocular acuity estimates were obtained on 36 normal infants, six each at ages 4, 8, and 16 weeks and 6, 9, and 12 months. Acuity estimate means and SD's agreed well with previously established preferential looking (PL) norms for each of the test ages. Time required for a monocular or a binocular test averaged 3 to 6 min.

Age Factors↗
PubMed1986

The relation of monocular optokinetic nystagmus to peripheral binocular interactions.

Human observers with deficient foveal stereopsis often show characteristic abnormalities of monocular optokinetic nystagmus (OKN). The present study examined the effect of binocular interactions in the peripheral visual field on these OKN deficits. A variety of binocular functions (binocular acuity summation, interocular suppression, motion-in-depth) were assessed at various positions throughout the visual field in subjects with deficient or no foveal stereopsis and related to monocular OKN deficits seen with different stimulus field sizes. Extent and location of peripheral binocular interactions accurately predicted the changes in monocular OKN observed with different field sizes. This indicates that the effects of early developmental conditions on cortical and subcortical binocularity, responsible for the deficits of stereopsis and OKN, show very close functional parallels. The results further suggested that monocular OKN deficits and peripheral acuity profiles are determined before the age of 5 yr.

Amblyopia↗
PubMed1986

Monocular and binocular optokinetic nystagmus in humans with defective stereopsis.

In order to investigate the previously suggested relation between cortical binocular function and deficits in monocular optokinetic nystagmus (OKN), monocular and binocular OKN was examined in normal, stereodeficient, and stereoblind observers, using a variety of stimulation velocities and stimulus field sizes. Most stereodeficient and stereoblind observers showed monocular OKN deficits in one or both eyes, which took the form of either a directional asymmetry or a reduction of the response in both directions. The deficits were often more pronounced at higher stimulation velocities and with smaller stimulus field sizes. The severity of the OKN deficit was related to the degree of residual foveal stereopsis, while the type of the deficit seemed to be influenced by the presence and depth of amblyopia. Binocular OKN resembled the best monocular response in subjects with a directional or ocular asymmetry. The results fit well with current animal models of the neural control of OKN.

Amblyopia↗
PubMed1984

Visuomotor behaviour of normal and corpus callosum-sectioned rats during interocular transfer.

The visuomotor behaviour of normal, control-operated and corpus callosum-sectioned hooded rats during interocular transfer of two visual discriminations was examined by means of video-recordings. All animals formed stereotyped running patterns in the training box during initial training. When tested for interocular transfer, callosum-sectioned rats showed more disorganized running patterns than normal or control-operated rats, although transfer of the discriminations was good. The results may indicate a role of the corpus callosum in visuomotor behaviour.

Animals↗
PubMed1984

Visual defects in children after cerebral hypoxia.

Visual functions were examined in 18 survivors of perinatal hypoxia/ischemia with mild to severe neurological sequelae, aged between 3 months and 17 years, and in two patients, aged 8 and 13 years, who had suffered postnatal hypoxic events. All but two patients showed clear visual deficits ranging from mild defects in visual acuity, visual field size, and/or optokinetic nystagmus to blindness. In 5 patients, the visual field was restricted to tunnel vision, a finding which appeared to be specifically related to the hypoxic/ischemic nature of the brain damage. The severity of the visual defects after perinatal hypoxia was related to the occurrence of neonatal seizures, later neurological outcome, and gestational age at birth. This is discussed in relation to previous studies of the effects of perinatal hypoxia/ischemia.

Adolescent↗
PubMed1983

On the relation of stereoacuity to interocular transfer of the motion and the tilt aftereffects.

Interocular transfer of both the motion and the tilt aftereffect were tested in 43 subjects with varying degrees of stereopsis, ranging from normal to stereoblind. Although there was an overall tendency for transfer to diminish with decreasing stereovision, stereoblind subjects always showed some transfer of the tilt aftereffect, and sometimes also of the motion aftereffect, while some subjects with normal stereothresholds had greatly reduced or no interocular transfer. No quantitative correlation between stereothresholds and amount of transfer could be found. The results indicate that there is no simple relationship between interocular transfer, stereopsis and cortical binocularity, as had been suggested previously.

Adaptation, Ocular↗
PubMed1983

Isolation of a mutant of Salmonella typhimurium strain TA1535 with decreased levels of glutathione (GSH-). Primary characterization and chemical mutagenesis studies.

A mutant of Salmonella typhimurium strain TA1535 with decreased glutathione (GSH) levels was isolated after treatment with UV and selection for N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) resistance; this GSH- mutant also exhibited increased resistance to MNNG, the methyl analog of ENNG. Estimation of the cellular GSH content showed that the GSH- derivative contained about 20% of the GSH levels found in TA1535. In mutagenicity tests (hisG46 leads to His+), the GSH- strain required the presence of GSH or L-cysteine in the medium for an optimal phenotypic expression and/or growth of spontaneous and induced His+ revertants, and may, therefore, be allelic to cys mutants of Salmonella described earlier. The mutagenic activity of MNNG, ENNG and 1,2-dibromoethane (DBE), but not that of N-ethylnitrosourea (ENU), was strongly reduced in TA1535/GSH-; pretreatment of the strain with GSH restored the mutagenicity of the first 3 chemicals to levels normally found in TA1535. The results support the current view that MNNG, ENNG and DBE, but not ENU, can be activated via reaction with GSH to species of higher reactivity and mutagenicity. It is concluded that the present GSH- strain can be used to study more systematically the role of GSH in the bioactivation and -deactivation of xenobiotics to mutagenic factors.

Drug Resistance, Microbial↗