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Biomedical subjects

P Jacobi

Publications and source records attributed to P Jacobi.

At least 19 recordsLinked to original sources

Expression of the CD15 differentiation antigen in the reproductive tract of the female rat during fetal and early postnatal ontogeny.

The expression of the (alpha1-->3)-fucosyl-N-acetyl-lactosamine (CD15) epitope in the genital tract of the female rat during fetal and early postnatal ontogeny was investigated by means of immunohistochemistry. CD15 was exclusively associated with epithelial cells and was mainly located along the cell membrane. The CD15 expression was characterized, firstly, by considerable differences within the various structures and even substructures of the genital tract and secondly, by the high degree of time-related changes which accompanied the morphological development. In the Mullerian duct, CD15 was present from embryonic day (E) 14 until birth on the apical membranes throughout the epithelial cell layer. In the Wolffian duct, CD15 expression was present between E16 and E19. Along the longitudinal extent of the Wolffian duct, expression intensity differed, showing moderate to high levels in the epithelial cells of the cranial and caudal parts, but without recognizable CD15 expression in the intermediate part. In the urogenital sinus, CD15 was expressed from E15 until E21. In the cranial parts, all epithelial cells were positive, whereas in the caudal parts, CD15 was present only on their apical membranes. In the ovarian tube, uterine horn, and vagina, a moderate to high CD15 expression at birth gradually diminished to very low levels during postnatal days (P) 8 and 9. After P9, re-expression of CD15 occurred in the caudal part of the ovarian tube and in the uterus, increasing to a maximum at about P32. The findings provide (indirect) evidence for a correlation between the intensity of CD15 immunoreactivity and the serum concentrations of estrogens as well as of estrogen receptors in the urogenital tract. Since steroid hormone dependency can be regarded as a gauge of the differentiation of malignancies, it would be worthwhile correlating CD15 levels with those parameters.

Animals

Hepatic retinopathia. Changes in retinal function.

In patients suffering from hepatic failure, the brain is subject to defined morphological and functional changes known as hepatic encephalopathia (HE). The morphological changes are dominated by glial cells (Alzheimer-type II astrocytes). It has recently been possible to demonstrate, that the retinal glia (Müller) cells undergo similar morphological changes. The present study was carried out in order to reveal if these Müller cell changes cause any characteristic functional deficits. We examined 11 patients with different stages of HE due to liver cirrhosis. Six patients were at stage 0 or 1 (group I) and five at stage 2 or 3 (group II). They underwent ophthalmological routine examination, colour vision testing and standard ERG recording. None of the patients reported impaired vision, in daylight or at night. There were no fundus abnormalities except very mild changes of the pigment epithelium and abnormal reflexes of the inner limiting membrane, especially in the higher HE stages. The number of confusions in the colour arrangement test increased with the higher stages of HE, preferably in the tritan axis. The scotopic a- and b-waves of the electroretinogram (ERG) were almost unchanged in group I and significantly decreased and delayed in group II. The photopic ERG b-wave amplitudes were changed in a similar fashion. Oscillatory potentials proved to be most sensitive to hepatotoxic changes. Their latencies were significantly delayed even in group I. Amplitudes were decreased significantly only in group II. Patients suffering from hepatic failure and accompanying HE display functional abnormalities of the retina. These are best demonstrated by the ERG, and correlate well with the degree of HE. A hypothesis is presented that relates the observed functional changes to altered neurotransmitter levels and impaired retinal glial-neuronal interaction, due to Müller cell damage caused by elevated ammonia levels.

Adult

The renin-angiotensin system--a possible neuromodulator in the human retina?

Morphology studies imply a possible contribution of the renin-angiotensin system (RAS) to neurotransmission in the mammalian retina. To investigate further the functional role of the RAS in the visual system of humans, we tested the effects of the angiotensin-converting enzyme (ACE) inhibitor Captopril (Capt; 25 mg) on electroretinogram (ERG) recordings, the cone flicker threshold (CFT), the FM-28-HUE test, and the psychophysical rod threshold in healthy volunteers. The parameters of renin, angiotensin, and blood pressure were controlled. We obtained the following results. First, Capt induced a significant decrease in amplitudes of the scotopic b-wave, oscillatory potentials, and the a-wave. The latency of responses to 30-Hz flicker was increased. Second, the CFT was reduced to a lower intensity, whereas the final rod threshold remained unchanged. These results are in accordance with previous immunocytochemical and electrophysiological data. They cannot be explained exclusively by the observed changes in systemic blood pressure. We conclude that the RAS may possibly be involved in retinal neurotransmission in humans in addition to its vascular effects.

Administration, Oral

Configuration of light responses in isolated retinal rods. A patch-clamp study.

The whole-cell patch-clamp technique was employed to investigate the light responses of single retinal rods of the frog (Rana esculenta and R. temporaria). In the majority of experiments, completely isolated cells were studied. Coupling with neighboring cells gave rise to a more complex response configuration. Responses were recorded under voltage-clamp and under current-clamp conditions. Stimulus response curves were measured in experiments with local stimuli illuminating only parts of the outer segment. Metabolic factors such as cGMP, GTP and ATP were also tested and were found to have specific and different influences on the response configurations. When the recording pipette was filled with an intracellular medium devoid of nucleotides, a retardation in the recovery of the light responses was observed during the course of an experiment. Addition of 1 mM ATP to the pipette medium prevented the larger part of the retardation, while 1 mM GTP accelerated the response recovery at the beginning of an experiment but did not prevent a subsequent retardation. Micromolar concentrations of cGMP were sufficient to elicit both a depolarization of the photoreceptor membrane and an increase in the response duration. These results show that, in single photoreceptors, the configuration of light responses not only depends on the stimulus parameters but also on those properties of the cells that are directly controlled by their nucleotide metabolism.

Adenosine Triphosphate

Size and chirality of intracellularly applied anions affect the function of isolated photoreceptors.

The effect of intracellularly applied anions on the function of retinal rods of the frog Rana esculenta was investigated by means of the whole-cell patch-clamp technique. When the recording pipette contained a medium based on potassium chloride, a slow spontaneous hyperpolarization was observed presumably due to a diffusional loss of the photoreceptor's internal transmitter cyclic guanosine monophosphate (cGMP) and its precursor guanosine triphosphate (GTP). When chloride was replaced by organic anions such as acetate, aspartate, or gluconate the speed of hyperpolarization diminished and the dark voltage of the rods was stabilized. The extent of stabilization correlates with the molecular weight of the anions. A significant difference in the stabilizing effect was found for L-aspartate and D-aspartate, suggesting an additional influence of the chirality. Effects of some of the anions on the configuration of the light responses were also observed.

Animals

Amantadine sulphate in treating Parkinson's disease: clinical effects, psychometric tests and serum concentrations.

Intravenous administration of amantadine has been shown to be a quick-acting and highly effective method of treating patients with Parkinson's disease. The duration of this therapeutic effect during long-term oral treatment has, however, remained controversial. Therefore, the effect of intravenous treatment was compared with long-term oral treatment over a period of 6 months. Clinical scores and psychometrically determined dexterity improved significantly during 10-day infusion therapy (200 mg amantadine sulphate/day). This improvement was successfully maintained by oral treatment (600 mg/day). A decrease in effectiveness was not observed. Reaction times were within the normal range for the age group involved and did not change significantly during the course of the study. Amantadine serum concentration during the infusion period ranged between 500 and 1000 micrograms/l and produced values nearly half as high as those obtained during oral treatment (600 mg/day). There was a constant relationship (quotient: 1.3) between serum and cerebrospinal fluid concentration. Considerable inter-individual variations were noted. A significant inter-individual correlation between serum concentration and clinical and psychological improvement was not discernible.

Administration, Oral

[Intravenous and oral treatment with amantadine sulfate in Parkinson disease].

The rapid efficacy of amantadine on akinesia and rigidity in Parkinson's disease is generally known. The duration of this therapeutic result is however controversial. Some authors have reported a loss of efficacy after only a few weeks of therapy. The success of a short-term parenteral and subsequently oral long-term treatment with amantadine sulphate in 8 Parkinsonian patients was tested by means of clinical and neuropsychological examinations and by monitoring the serum concentration over the course of half a year. A ten-day intravenous treatment with amantadine sulphate (200 mg daily) led to a significant improvement in the clinical and psychological test results. This attained improvement could be maintained for 6 months with oral therapy consisting of 600 mg amantadine sulphate. There were strong interindividual variations in serum concentration.

Administration, Oral

No disturbance of myelination in the central nervous system by selective 3H beta-irradiation.

The effect of a selective irradiation of myelin by 3H beta-particles was studied by light and electron microscopic methods in guinea pig spinal cord. The animals were injected with [3H]leucine shortly after birth when the rate of myelin biosynthesis is high and sacrificed 130 days later. In spinal cord the radioactivity was mainly preserved in myelin because the half life of myelin proteins is much higher than that of most other CNS proteins. As a consequence the irradiation dose in the white matter was much higher than in the gray matter. In myelin internally irradiated by 3H beta-particles within 130 days at a dose of 10 Gy no alterations could be detected either by morphological or by morphometric methods.

Animals

[Exogenous psychoses in Parkinson syndrome. Frequency and causal conditions].

Exogenous psychotic symptoms of a wide variety have been reported to appear more and more frequently since the introduction of levodopa in the therapy of Parkinson's disease. They were considered to be caused by treatment related imbalance of cerebral neurotransmitters and hypersensitivity of the dopaminergic receptors, respectively. In the present investigation an analysis was done concerning the relevance of different antiparkinsonian drugs and other factors such as severity of neurological and cerebroorganic symptomatology, age, duration of treatment, EEG and brain atrophic changes and additional physical diseases for the appearance of psychotic symptoms. The questions were posed to 152 patients (54 men, 88 women) aged 34-76 years, which received a treatment with levodopa alone, in combination with a decarboxylase inhibitor, amantadines and/or anticholinergics for a period of 1-9 years. An exogenous psychotic symptomatology was observed in 42 patients (27,6%), explicitly under all antiparkinsonistic drugs, but not when amantadines were given as the initial treatment. In patients receiving levodopa/decarboxylase inhibitor psychotic symptoms could be observed most frequently but at the same time the duration of treatment was the longest. In 15 patients psychotic symptoms appeared under different antiparkinsonian drugs. In 28 patients this symptomatology was followed by a constant severe dementia. Predisposing factors for exogenous psychosis proved to be: a higher age at the beginning of the treatment and the initiation of treatment, a pronounced neurological symptomatology and signs of dementia as well as additional physical diseases. Because of the very complex conditions under which exogenous psychosis can be observed and the additional fact that they can appear under each antiparkinsonian substance, levodopa cannot be considered as the sole cause.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Effects of synthetic neuropeptides in psycho-organic brain syndrome. Results with ACTH4-10 and ACTH4-9-analog (author's transl)].

The effects of ACTH4-10 (Org O163) and of the ACTH4-9 analog (Org 2766) were tested in 20 male patients suffering from a mild to moderate cerebroorganic impairment. Patients were aged between 51-72 years (mean 60.9). Org 2766 was given in dosages of 0.05 mg, 0.5 mg and 5 mg, Org O163 in a dosage of 30 mg. The investigation was based on a randomized incomplete crossover design. By means of psychological tests the effects of the synthetic neuropeptides on memory, state of well-being, attention, vigilance and psychomotor function were investigated. The statistical analysis of the results did not reveal any effects of both substances on the functions tested. These results are in agreement with those of other studies in man using similar methods and acute administration of ACTH4-10 and/or Org 2766. In such studies only effects of reactive inhibition of attention and motivation could be demonstrated consistently.

Adrenocorticotropic Hormone

Bacterial elimination and therapeutic effectiveness under different schedules of amoxicillin administration.

Bacterial elimination kinetics under different simulated administration schedules of amoxicillin was followed in vitro by using a simple model for simulation of pharmacokinetic parameters. The results were compared to those obtained in lethally infected mice by determining the viable bacterial count in the blood at various times post-infection and under different schedules of amoxicillin administration. A satisfactory correlation could be established between the in vitro and in vivo results. Multiple administration of amoxicillin was found to induce a beta-lactamase in vitro as well as in vivo in the Escherichia coli strain used. No difference was however found between the various administration schedules of amoxicillin in terms of surviving animals. Taking into account the lasting elimination of viable bacteria from the blood, the best treatment of E. coli-infected mice was found to be a twice daily administration of the higher amoxicillin dose.

Amoxicillin

The course of brain atrophy in Parkinson's disease.

In 110 parkinsonian patients (53 men, 57 woman) aged 38--81 years, computer-tomographic follow-up investigations were done to assess the development of brain atrophy. The control examinations were done after an average of 28 months. At that time an increase in brain atrophic changes of different localization could be observed in 23% of the patients. In addition, it could be demonstrated that the increase in pathologic CT findings is to be observed especially in patients with higher age, a more marked impairment in psycho-organic capacity, more pronounced handicaps in the fine-motorial performances at the beginning of the study. From the neuroradiological point of view, patients with more marked pathologic CT findings upon the first examination, be these ventricular enlargement and/or cortical atrophy, more often showed a progression of brain atrophy.

Adult