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Biomedical subjects

P Schulz

Publications and source records attributed to P Schulz.

At least 37 records · Page 2Linked to original sources

Alternating episodes of vestibular nerve excitation and failure.

Recurrent episodes of oscillopsia, rotational vertigo, and postural imbalance were elicited and modulated by changing the horizontal head positions of a patient with an arachnoid cyst in the right cerebellopontine angle that distorted the vestibulocochlear nerve. Oculomotor analysis revealed two different types of attacks depending on the particular head position: 1) episodes of vestibular hypofunction (minutes to several hours) with normal head position and 2) paroxysmal vestibular excitation (seconds) with head rotation to the left. The most likely cause is a transition from conduction block to ectopic discharges, which occurs when various peripheral nerves are compressed. One week after resection of the cyst and decompression of the eighth cranial nerve the patient was symptom free, and the electronystagmogram was normal.

Arachnoid Cysts↗

Reward dependence is positively related to urinary monoamines in normal men.

According to Cloninger, three major personality dimensions, novelty seeking, harm avoidance, and reward dependence, are dependent on central monoaminergic systems. This study examined the relationship between the urinary levels of different monoamines and the above personality dimensions. Fifty normal men answered the Tridimensional Personality Questionnaire (TPQ); their levels of dopamine, norepinephrine, epinephrine, normetanephrine, metanephrine, 3-methoxy-4-hydroxyphenylglycol, vanilmandelic acid, homovanilic acid, and serotonin metabolite 5-hydroxyindolacetic acid were measured in urine on two consecutive nights. Significant and positive correlations were found between reward dependence, 3-methoxy-4-hydroxyphenylglycol, and epinephrine (r = .50 and r = .51, respectively). Monoamine levels explained 44% of the variance of reward dependence. Cluster analysis identified three groups of subjects presenting specific patterns of monoamine excretion. The TPQ scores could discriminate among subjects belonging to these clusters. These results point out a narrow relationship between urinary monoamine excretion and the basic personality dimension of reward dependence.

Adult↗

Issues in the development of medical products based on human plasma.

Product development and process validation are shown in the case of several products obtained from human plasma. These are virus-inactivated plasma, intravenous immunoglobulins and the clotting factors VIII and IX. Different analytical methods are presented, which are used for product control and in-process control. For the production of virus-inactivated human plasma a down-scale protocol is presented, allowing a simulation of the production on a laboratory scale. Virus validation has shown that the reduction of transfusion-relevant viruses in the process was higher than six log steps. Determination of leachables from the RP-column, which was used in this production, proved that they appear in the final product in quantities below the detection limits only. It was also shown that the chemicals used for virus inactivation could be quantitatively removed from the product. For the isolation of other products, here intravenous gamma globulins and the clotting factors VIII and IX, similar validation steps had to be taken. In the case of clotting factor VIII the following data were determined, the reduction of viruses, the amount of leachables from the column, the residues of chemicals from the solvent/detergent treatment for virus inactivation. Virus reduction was successfully performed as well as the removal of chemicals used for virus inactivation. The amount of leachables from the columns used for chromatographic purification was found to be far below the permissible levels.

Biological Products↗

Lower sex hormones in men during anticipatory stress.

Free cortisol, luteinizing hormone (LH), total testosterone and monoamines were measured in two successive nocturnal urine collections in 50 healthy men to assess the influence of anticipatory stress. The first collection (N-2) was two nights before and the second (N-1) was just on the night before a one-day experimental stressor consisting of participation in a one-day clinical research protocol. The mean cortisol level increased from 23.4 (N-2) to 66.6 micrograms (N-1), while mean LH level decreased from 2.68 (N-2) to 1.71 IU (N-1) and the mean testosterone level fell from 1.31 (N-2) to 0.70 microgram (N-1). There were no changes in monoamines. Inhibition of sex hormones is a relatively neglected area of stress research.

Adult↗

Day-to-day intraindividual reliability and interindividual differences in monoamines excretion.

The urine of 44 normal men was collected during 2 nights to evaluate components of biological variation, i.e., intraindividual day-to-day variability and interindividual variability in monoamines excretion. Monoamines presented important interindividual variability [interindividual coefficients of variation (%): dopamine 18.3, norepinephrine 66.7, epinephrine 85.3, normetanephrine 22.4, metanephrine 76.8, 3-methoxy-4-hydroxyphenylglycol (MHPG) 77.0, vanilmandelic acid (VMA) 64.3, homovanilic acid (HVA) 71.3, 5-hydroxyindolacetic acid (5-HIAA) 20.4]. The reliability of these amounts was high, with intraclass correlation coefficients ranging from 0.43 (P < 0.001) for MHPG free form to 0.65 (P < 10(-6)) for dopamine and normetanephrine (intraindividual coefficients of variation (%): dopamine 8.5, norepinephrine 39.9, epinephrine 45.9, normetanephrine 10.3, metanephrine 46.3, MHPG 37.5, VMA 30.7, HVA 41.0, 5-HIAA 12.3).

Adult↗

Expression of ionotropic glutamate receptor subunit mRNAs by paraventricular corticotropin-releasing factor (CRF) neurons.

To determine whether paraventricular corticotropin-releasing factor (CRF) neurons express NMDA, AMPA or kainate-preferring glutamate receptors, we have colocalized, by in situ hybridization (ISH), transcripts of various glutamate receptor subunit genes with the CRF messenger RNA on doublet adjacent sections of the rat hypothalamus. We found that more than 70% of CRF-positive neurons contain the NMDA receptor subunit NR1 mRNA whereas NR2A and NR2B subunit mRNAs were not detectable in CRF cells. A significant proportion of identified CRF cells express AMPA receptor subunit GluRA (46%), GluRB (21%) as well as the kainate-preferring receptor subunit KA2 (31%) mRNAs. These results support the hypothesis that the excitatory transmitter glutamate may directly influence CRF neurons through NMDA as well as non-NMDA receptors.

Animals↗

Parallel nocturnal secretion of melatonin and testosterone in the plasma of normal men.

Differences and similarities in the temporal organization of hormone secretion in plasma reflect the activity of CNS pacemakers. One aspect of this activity, the temporal synchronization of the secretion of different hormones is still poorly understood. We report the analysis of melatonin and testosterone plasma concentrations during two nights in 6 normal healthy young men. Blood was collected every 20 min between 2040 and 0640. Plasma testosterone concentrations increased by 1.5- to 2-fold during the second part of the night, and melatonin by 2.5- to 4-fold. In each subject, the individual temporal pattern of melatonin was quite stable over the two nights of sampling, while testosterone profiles showed fluctuations. There was a high degree of parallelism in these two hormones nocturnal secretion. These results, together with previous studies, suggest that melatonin might entrain the nocturnal secretion of testosterone.

Activity Cycles↗

Mucosal model of immunization against human immunodeficiency virus type 1 with a chimeric influenza virus.

Previously, we constructed a chimeric influenza virus that expresses the highly conserved amino acid sequence ELDKWA of gp41 of human immunodeficiency virus type 1 (HIV-1). Antisera elicited in mice by infection with this chimeric virus showed neutralizing activity against distantly related HIV-1 isolates (T. Muster, R. Guinea, A. Trkola, M. Purtscher, A. Klima, F. Steindl, P. Palese, and H. Katinger, J. Virol. 68:4031-4034, 1994). In the present study, we demonstrated that intranasal immunizations with this chimeric virus are also able to induce a humoral immune response at the mucosal level. The immunized mice had ELDKWA-specific immunoglobulins A in respiratory, intestinal, and vaginal secretions. Sustained levels of these secretory immunoglobulins A were detectable for more than 1 year after immunization. The results show that influenza virus can be used to efficiently induce secretory antibodies against antigens from foreign pathogens. Since long-lasting mucosal immunity in the genital and intestinal tracts might be essential for protective immunity against HIV-1, influenza virus appears to be a promising vector for HIV-1-derived immunogens.

AIDS Vaccines↗

Corticotropin-releasing factor and vasopressin mRNA levels in roman high- and low-avoidance rats: response to open-field exposure.

Roman high- (RHA) and low- (RLA) avoidance rats are selected and bred for rapid versus non-acquisition of two-way, active avoidance behavior in a shuttle box. They also show a number of other behavioral differences which appear to be essentially related to emotional factors, the RLA rats being emotionally more sensitive. The ACTH secretory response to stressors is also augmented in RLA rats. We thus raised the question whether the expression of corticotropin-releasing factor (CRF) and vasopressin (VP), two neurohormones exerting a synergistic action on ACTH release from corticotropic cells, is different in the two strains. Steady-state mRNA levels were examined in the parvicellular neurons of the paraventricular nucleus under basal conditions and 4 h after a single 8-min exposure to an open-field stressor. In situ hybridization histochemistry with 35S-labeled oligonucleotide probes was followed by quantitative cell by cell autoradiography. When basal CRF and VP mRNA levels were compared in the two lines, we found that the RLA rats had a significantly higher VP-labeling density than the RHA rats. No difference was found for CRF mRNA. During open-field exposure, we observed behavioral differences paralleled by elevated corticosterone compatible with an increased emotional response in RLA rats. Open-field exposure produced a significant increase in CRF but not VP mRNA in both RHA and RLA rats (by 43 and 57%, respectively). These results suggest that differences in basal VP expression in CRF neurons may participate in the mechanisms underlying the hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis in the emotionally more sensitive RLA rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

NK1 receptor expression by cholinergic interneurones in human striatum.

Neurokinin-1 (NK1) receptor expression in human striatum was analysed using the polymerase chain reaction. To determine whether cholinergic interneurones express this receptor, in situ hybridization histochemistry was then applied to caudate nucleus and putamen. Radioactive oligonucleotide probes specific for choline acetyltransferase (ChAT) and NK1 receptor mRNA were used on adjacent cryostat sections. All of the 160 identified neurones positive for ChAT were also labelled for NK1 receptor. Moreover, in the caudate nucleus, NK1 receptor mRNA was detected in a population of large neurones that were not cholinergic. These results are consistent with the hypothesis that NK1 receptor-mediated mechanisms are involved in the function of cholinergic interneurones. This might be relevant to pharmacological or pathophysiological situations where substance P inputs are modified.

Aged↗

Neuroendocrine and psychological effects of restricted environmental stimulation technique in a flotation tank.

The restricted environmental stimulation technique or REST is a method of relaxation where the level of environmental sensory inputs is kept very low. A particular REST technique called tank flotation, or flotation REST, consists of 1 h sessions in a tank containing water with a high salt content and maintained at 35.5 degrees C. In this protocol, five normal subjects were studied before and during 2 h after a 60 min flotation REST session and a control session of 60 min in a supine position on a bed. Cortisol, thyreostimulating hormone (TSH), thyroxine (T4), prolactin, melatonin, luteinizing hormone (LH), growth hormone (GH), beta-endorphin, vasopressin (ADH), gamma-aminobutyric acid (GABA) and homovanillic acid (HVA) were measured in plasma. HVA, 5-hydroxy-indoleacetic acid (5-HIAA) and vanylmandelic acid (VMA) were measured in urine. There were no changes in hormones concentrations that could be attributed to flotation REST. The urinary excretion of VMA was lower after the flotation REST session. The psychological consequences of flotation REST were more easily demonstrated than the neuroendocrine changes that are assumed to reflect the state of relaxation. Flotation REST increased subjective levels of sedation and euphoria. The possible mechanisms by which flotation REST induces relaxation are discussed.

Adult↗

Biological uniqueness and the definition of normality. Part 1--The concept of 'intrinsic' homeostasis.

The patterns of biochemical and physiological variables values are subject-specific and quite stable over time. Thus, within the limits imposed by physiological requirements, the composition of the 'milieu intérieur' varies between individuals. It follows that having all values of blood constituents within the norm (defined statistically from populations of healthy subjects) might not be sufficient to identify biological normality, and a revised definition of biological normality should take into account inter-individual differences. Our concept of 'intrinsic' homeostasis means that the differences between subjects' concentrations of blood constituents express subject-specific constraints in the organization of their physiology, and that these differences might play a greater role than usually recognized. We list the consequences for medical research of the existence of biological uniqueness and propose to give more importance to the study of biological 'fingerprints' and 'intrinsic' homeostasis in physiology and clinical medicine.

Homeostasis↗

Biological uniqueness and the definition of normality. Part 2--The endocrine 'fingerprint' of healthy adults.

In an accompanying paper, we discussed the relevance of biological uniqueness for research in physiology and medicine. We proposed the concepts of subject-specific homeostasis, or 'intrinsic' homeostasis. Here, we illustrate this concept with the example of the endocrine 'fingerprint'. 9 hormones were measured in the blood of 8 normal subjects during 2 consecutive mornings, under a standardised resting condition. The concentrations of the hormones were subject-specific. They varied up to 6-fold between subjects, but were stable from one day to the next for each individual. TSH and FSH showed the wider inter-individual range of values, together with a very high level of day-to-day stability (r = 0.99 in both cases). In contrast, the inter-individual range of cortisol concentration was the smallest (1.5-fold) and the day-to-day stability of cortisol concentrations within each subject was low. A total of 21 non-hormonal variables were also measured. They varied less than hormones between subjects, but, with the exception of the electrolytes, most showed stability over the 2 days of sampling. We conclude that the organisation of hormonal and non-hormonal homeostasis varies between subjects to a greater extent than generally acknowledged and suggest that these differences express subject-specific constraints in the organization of homeostasis.

Adult↗

Plasma concentration of nine hormones and neurotransmitters during usual activities or constant bed rest for 34 H.

Thyroid-stimulating hormone (TSH), cortisol, melatonin, prolactin, luteinizing hormone (LH), delta-sleep-inducing peptide (DSIP), its phosphorylated form (P-DSIP), heart rate, and body temperature were measured every half hour during two 24-h periods in five normal men. tau-Amino-butyric acid (GABA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured less frequently. The first period, the "activity" condition, included usual daily activities. The second period, or "rest" condition, consisted of fasting, constant bed rest during 34 h, and partial light deprivation. Compared with the "rest" condition, the "activity" condition increased heart rate, temperature, LH, and TSH in most subjects, and cortisol in two of five subjects. It retarded the onset of nocturnal cortisol and melatonin secretion. The temporal pattern and the absolute values of the concentrations of DSIP, P-DSIP, MHPG, GABA, and prolactin showed no or minimal changes during the two conditions. In spite of the influence of the "activity" versus "rest" condition on several hormones, the mean concentrations as well as the temporal organization of their secretion into plasma were quite stable within each subject, whereas they varied much more between individuals. TSH, cortisol, and melatonin values were also stable within an 8-month period in one subject who was studied on four occasions. The results illustrate that the patterns of hormones rhythms and their reactivity to changes in the environment are, to a large extent, specific to each subject.

Adult↗

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Historiography↗

Correlation of vascular morphology with clinical types in cholesteatoma of the middle ear.

Cholesteatoma is characterized by the presence of hyperproliferative keratinizing squamous epithelium in the middle ear cavity. The abundance and morphology of blood vessels in the stroma of cholesteatoma was investigated using a monoclonal antibody against an endothelial cell marker, factor VIII-related antigen. Normal skin sections were stained for comparison. In cholesteatoma tissue blood vessels frequently were more numerous and smaller in caliber than in normal skin. The pattern of vascularization differed between the pearly and the dendritic type of cholesteatoma. In the dendritic type capillaries with uniform diameter prevailed, whereas the pearly type showed blood vessels of variable caliber with a clearly visible lumen. This hypervascularization observed in cholesteatoma may be induced by factors released from infiltrating immune cells and the squamous epithelium and could play an important role in sustaining the continuous abnormal growth of the cholesteatoma.

Antibodies, Monoclonal↗

Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor.

A cDNA clone encoding a 53 kd serine/threonine kinase receptor with an overall structure similar to that of the type II receptor for transforming growth factor beta (TGF beta) was obtained. 125I-TGF beta 1 bound to porcine endothelial cells transfected with the cDNA and formed a cross-linked complex of 70 kd, characteristic of a TGF beta type I receptor. Immunoprecipitation of the cross-linked complexes by antibodies against the cloned receptor revealed the 70 kd complex as well as a 94 kd TGF beta type II receptor complex. The immunoprecipitated novel serine/threonine kinase receptor had biochemical properties of the TGF beta type I receptor and was observed in different cell types. Transfection of the cloned cDNA into TGF beta type I receptor-deficient cells restored TGF beta-induced plasminogen activator inhibitor 1 production. These results suggest that signal transduction by TGF beta involves the formation of a heteromeric complex of two different serine/threonine kinase receptors.

Amino Acid Sequence↗

Coexpression of dopamine D2 and substance P (neurokinin-1) receptor messenger RNAs by a subpopulation of cholinergic neurons in the rat striatum.

Amongst different intrinsic and extrinsic inputs, cholinergic striatal interneurons receive afferents from the dopaminergic nigrostriatal projection and from local collaterals of striatonigral cells containing substance P. The following study demonstrates that both dopamine D2 and substance P (neurokinin-1) receptors are expressed by a large proportion of cholinergic interneurons. Using in situ hybridization on triplet adjacent sections with radioactive probes specific for choline acetyltransferase, substance P receptor, and D2 receptor long-splicing form messenger RNAs, we show that these interneurons can be divided into four subpopulations in terms of substance P and D2 receptor expression. A majority of these neurons coexpress both receptors (76%), while other minor subpopulations express either one (respectively, 16% and 2%) or none of them (6%). Our results also show that substance P receptor is expressed by striatal neurons that are not cholinergic. These findings are in agreement with the concept that striatal cholinergic interneurons are heterogeneous in terms of input-output connections and the type of receptors expressed. Moreover, the presence of substance P and D2 receptors on a majority of these neurons is relevant to a putative role of cholinergic interneurons in several conditions such as various neurodegenerative disorders or antipsychotic drug administration, where substance P and dopamine inputs are modified.

Animals↗