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R Schmidt

Publications and source records attributed to R Schmidt.

At least 379 records · Page 21Linked to original sources
PubMed1994

Cyclic beta-casomorphin analogues with mixed mu agonist/delta antagonist properties: synthesis, pharmacological characterization, and conformational aspects.

Analogues of the potent and moderately mu-opioid-receptor-selective cyclic beta-casomorphin-5 derivative H-Tyr-c[-D-Orn-Phe-D-Pro-Gly-] (2) were prepared by conventional solution synthesis. Replacement of the Phe3 residue by 2-naphthylalanine (2-Nal) led to a peptide (4) with high affinity for both mu and delta opioid receptors. This compound turned out to be an agonist in the mu-receptor-representative guinea pig ileum (GPI) assay but a moderately potent antagonist against various delta agonists in the delta-receptor-representative mouse vas deferens (MVD) assay. It thus represents the first known cyclic opioid peptide analogue with mixed mu agonist/delta antagonist properties. Interestingly, replacement of 2-Nal3 in compound 4 with 1-naphthylalanine (1-Nal) resulted in an analogue (5) showing high affinity for mu receptors and a full agonist effect in the MVD assay that was mediated by both mu and delta receptors. Substitution of Trp for Phe3 in 2 (compound 8) was well tolerated at both receptors and led to an analogue with agonist activity in both the GPI and MVD assays. Variation of the peptide ring size in 4 was achieved by substitution of D-Orn2 with D-Lys (compound 6) or D-2,4-diaminobutyric acid (compound 7). Analogue 6 was also a mixed mu agonist/delta antagonist with somewhat lower potency than 4, whereas compound 7 displayed mu agonist and partial delta agonist properties. Further reduction of the peptide ring size, as achieved by deletion of the Gly5 residue, produced a compound (9) which was a full agonist in both bioassays. Conformational analysis of analogues 2, 4, and 5 by 1H NMR spectroscopy and molecular mechanics studies suggested that the overall conformation of parent compound 2 and the 2-Nal-containing peptide 4 was similar, while the side-chain orientation of 1-Nal in peptide 5 was different. These results suggest that the delta antagonist properties of analogue 4 may not be due to a difference in its overall conformation as compared to the agonist 2 but may be a direct effect of the 2-naphthyl moiety per se preventing proper alignment of the peptide for receptor activation.

Amino Acid Sequence↗
PubMed1994

Preoperative evaluation of abnormal mammographic findings to avoid unnecessary breast biopsies.

OBJECTIVE: To prospectively evaluate a program of additional mammographic views, interval follow-up, and stereotactic biopsy in the management of abnormalities detected on mammograms. METHODS: From June 1988 to September 1991, 267 consecutive women who were referred for surgical consultation because of an abnormal mammographic finding were evaluated. Mammographic abnormalities were assessed as benign or as requiring interval follow-up, stereotactic biopsy, open surgical biopsy, or additional views. Women having additional mammographic views were reassigned to the preceding groups. The mean follow-up for women who did not have a biopsy was 37 months. RESULTS: Only 129 (48%) of the women who were sent for surgical consultation underwent open biopsy, and 46 (36%) of the biopsy specimens revealed carcinoma. Forty-one (89%) of the cancers were ductal carcinoma in situ or stage I lesions. Of the 117 women who were assigned to follow-up, six (5%) subsequently required biopsy and two cancers were identified. CONCLUSION: Rigorous mammographic evaluation and the use of stereotactic biopsy for selected lesions can prevent breast biopsy for low-suspicion mammographic abnormalities while still allowing the detection of early-stage breast cancer.

Adult↗
PubMed1994

Responsiveness of the somatosensory system after nerve injury and amputation in the human hand.

We studied the responsiveness of the somatosensory system in humans after prolonged deprivation of peripheral input. Eight patients with traumatic transection of the median or ulnar nerve and 6 patients with amputation of a finger or hand underwent microneurography and intraneural stimulation. Bundles of nerve fibers were electrically stimulated through a microelectrode placed in the affected nerve proximally to the site of damage or in the case of amputees, in a nerve fascicle supplying the stump. During intraneural stimulation the subjects with nerve injuries reported distinct percepts in the hypoesthetic skin. Their projections were usually confined to the territory of a single or two adjacent palmar digital nerves, similar to the fascicular territories of healthy nerves in control subjects, but there was much less microneurographically recordable afferent activity than in normal subjects. In amputees intraneural stimulation evoked sensations in a phantom digit or digits in over three fourths of the fascicles studied. We conclude that (1) the somatosensory system remains able to process information from a nerve fascicle that has lost its cutaneous territory, and (2) somatosensory localization remains accurate despite the presumed central reorganization that takes place after nerve division or amputation. This lack of functional adaptation has important implications with regard to our understanding of human central nervous system plasticity.

Adolescent↗
PubMed1994

Structure and function of the frontal pit of Lipoptena spp. (Diptera: Hippoboscidae).

Scanning electron microscopy and histological techniques were used to study the structure and possible function of the frontal pit present in the frons of Lipoptena annalizeae. In the adult fly the opening leads into a closed sclerotized tube (torma) within a sclerite (fulcrum), to which the cibarial pump muscles are attached enabling the retraction of the proboscis. A method for softening the heads of Lipoptena for histological studies is also described.

Animals↗
PubMed1994

Improvement of epidermal differentiation and barrier function in reconstructed human skin after grafting onto athymic nude mice.

To determine whether epidermis reconstructed in vitro at the air-liquid interface on de-epidermized dermis has the capacity to normalize the expression of differentiation-specific markers, its lipid composition and stratum corneum barrier properties, human skin equivalents were transplanted onto athymic nude mice and investigated at different stages ranging from 1 to 4 months after grafting. Indirect immunofluorescence with species- or non-species-specific antibodies revealed that as early as 1 month after transplantation keratinization, and involucrin, loricrin and transglutaminase patterns were normalized. Human melanocytes were observed in the basal layer of the pigmented graft. As revealed by high-performance thin-layer chromatography and transmission electron microscopy after ruthenium tetroxide fixation, the lipid profile and the intracellular lamellar organization were similar to those found in natural epidermis. Transepidermal water loss measurements and penetration studies showed that the barrier properties of the reconstructed epidermis after transplantation were comparable to those of normal human skin.

Animals↗
PubMed1994

Infradiaphragmatic bronchogenic cyst with high CT numbers in a boy with primitive neuroectodermal tumor.

Abdominal bronchogenic cysts are very rare with less than 20 published cases. We report the case of a retroperitoneal bronchogenic cyst in a 12-year-old boy, who initially presented with a primitive neuroectodermal tumor of the pelvis. Computed tomography (CT) showed a small, hyperdense nonenhancing mass adjacent to the right crus of the diaphragm. Follow-up CT after chemotherapy showed a decrease in CT attenuation of this mass, but a slight increase in size. At surgery the mass was loosely attached to the diaphragm and final pathology confirmed the diagnosis of a bronchogenic cyst.

Bronchogenic Cyst↗
PubMed1994

Phe1-substituted beta-casomorphin-5 analogues with analgesic activity.

The antinociceptive potency of linear and cyclic beta-casomorphin-5 (CM-5) analogues, modified in position 1 by substitution of the tyrosine (Tyr) by the phenylalanine (Phe) residue, was studied using the vocalization test. With the exception of the linear [Phe1,D-Orn2]CM-5, the Phe1-substituted linear and cyclic casomorphin analogues exhibit remarkable analgesic potency compared to morphine, although the opioid receptor affinity and the opioid activity in vitro is diminished compared to the corresponding Tyr-containing analogues. The analgesic effect of the compounds is mediated by activation of opioid receptors, because it can be antagonized with naloxone. Furthermore, it was demonstrated that the [Phe1,D-Orn2,D-Pro4]CM-5, which was about sixfold more potent than morphine, developed cross-tolerance to morphine.

Amino Acid Sequence↗
PubMed1994

Aorto-caval fistula--an uncommon complication of infrarenal aortic aneurysms.

Aorto-caval fistulas are an uncommon complication of infrarenal aortic aneurysms, being found in 0.22% to 6.04% of all cases. Operating on 1231 patients with abdominal aortic aneurysm in the last 30 years we saw 17 patients with an aortocaval fistula. While 5 patients showed an isolated fistula, 12 had an additional rupture of the aneurysm into the retroperitoneal space or the abdominal cavity. Only in four patients was the aorto-caval fistula diagnosed preoperatively. In 16 patients the fistula was closed from within the aorta. One patient needed ligation of the vena cava and the iliac veins. Mortality rate was 40% in the group with isolated fistula and 66.7% in the group with concomitant rupture. Aorto-caval fistula is a severe complication of abdominal aortic aneurysms, which may be fatal and demands early diagnosis and prompt treatment.

Aged↗
PubMed1994

[Do estrogens have an antipsychotic action?].

Within the framework of our ABC study, an epidemiological study on schizophrenia (Häfner et al., 1989, 1991 a; Riecher et al., 1991), we were able to show that the mean age at onset of the disease is 3-4 years higher in women than in men and that women have a second peak of onsets after 45 years of age. In a systematic analysis we developed and tested different psychosocial and biological explantory hypotheses. The oestrogen hypothesis could be identified in the course of this analysis as the most plausible one. According to this hypothesis (Häfner, 1987) female sex hormones enhance the vulnerability threshold for schizophrenia. In this case women from puberty to (pre-)menopause would be protected from the outbreak of the disease to a certain extent by their high physiological oestradiol production; they would, however, later "draw level" in respect of morbidity risk. Animal experiments conducted to test this hypothesis and to explain the underlying pathophysiological mechanism implied that oestradiol can modulate the sensitivity of dopamine-D2-receptors in the brain (Häfner et al., 1991 b; Gattaz et al., 1992). In the clinical study presented, we examined the validity of the oestrogen hypothesis in humans. We tested, whether the acute symptomatology of schizophrenic patients fluctuates with oestradiol serum levels during the female menstrual cycle. We examined 32 acutely admitted schizophrenic women during their hospital stay by analysing hormonal parameters and applying various rating scales for psychopathology on certain days of the cycle. A significant association emerged between oestradiol levels on the one hand, and psychiatric symptomatology, behaviour on ward, paranoid tendencies and general well-being, on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Inner ear blood flow with betahistine--an animal experiment study].

The influence of the drug Betahistin on the cochlear blood flow (CBF) was checked on 15 guinea pigs (6 controls) (Charles River, BFA 350-450 g) by means of the hydrogen clearance method. The hydrogen clearance measurements were carried out under alpha-chloralose-ethylurethane anaesthesia, artificial respiration with simultaneous control of the electrocardiogram, arterial blood pressure and body temperature. The actual arterial pH-value was checked hourly. Indirect measurement of CBF was carried out in the perilymphatic space (basal turn) before and after intravenous application of Betahistin (vena jugularis externa) (dosage: 0.11 mg/kg/min). The mean arterial blood pressure remained within the 10% range during the experiments. Under Betahistin-treatment the CBF showed an significant increase (p = 0.05). Despite this favourable pharmacological efficiency of Betahistin it must be pointed out that the general application of vasoactive drugs, especially of vasodilative drugs, in the treatment of postulated inner ear blood flow disturbances is presently controversial.

Animals↗
PubMed1994

Can estradiol modulate schizophrenic symptomatology?

Using epidemiologic data, in an earlier study we formulated the hypothesis that estrogens can delay the onset of schizophrenia in females by raising the vulnerability threshold for this disease. In animal experiments, Häfner and colleagues found evidence that chronic estradiol treatment reduces the sensitivity of dopamine (D2) receptors in the brain. In the clinical study presented in this article, as a further step we examined the antipsychotic properties of estradiol in human females by testing whether schizophrenic symptomatology varies with estradiol serum levels throughout the menstrual cycle. We examined 32 acutely admitted female schizophrenia patients (Present State Examination/CATEGO diagnosis, ICD-9) with a history of regular menstrual cycles, ages 18 to 43 (mean = 30.5), during their hospital stays (3-8 weeks), analyzing hormonal parameters and applying various rating scales for psychopathology every 7 days. In all patients, estradiol serum levels were markedly reduced as compared with the normal population, and fluctuations throughout the cycle were dampened. Nevertheless, a significant association emerged between estradiol levels, on the one hand, and psychopathology scores, on the other--that is, the psychiatric symptomatology as assessed by the clinical psychiatrist (Brief Psychiatric Rating Scale, p < or = 0.01), behavior on the ward as assessed by the nursing staff (Nurses' Observation Scale for Inpatient Evaluation p < or = 0.01), paranoid tendencies and general well-being as assessed by the patients themselves (Paranoid-Depressivitäts-Skala paranoid score p < or = 0.05; Befindlichkeits-Skala p < or = 0.05). Psychopathology seems to improve when estradiol levels rise, and vice versa. These findings can be interpreted as further evidence for a protective effect of estrogens in schizophrenia, possibly due to the known anti-dopaminergic activities of these hormones.

Adolescent↗
PubMed1994

Analysis of clones carrying repeated DNA sequences in two YAC libraries of Arabidopsis thaliana DNA.

YAC clones carrying repeated DNA sequences from the Arabidopsis thaliana genome have been characterized in two widely used Arabidopsis YAC libraries, the EG library and the EW library. Ribosomal, chloroplast and the paracentromeric repeat sequences are differentially represented in the two libraries. The coordinates of YAC clones hybridizing to these sequences are given. A high proportion of EG YAC clones were classified as containing chimaeric inserts because individual clones carried unique sequences and repetitive sequences originating from different locations in the genome. None of the EW YAC clones analysed were chimaeric in this way. YAC clones carrying tandemly repeated sequences, such as the paracentromeric or rDNA sequences, exhibited a high degree of instability. These observations need to be taken into account when using these libraries in the development of a physical map of the Arabidopsis genome and in chromosome walking experiments.

Arabidopsis↗
PubMed1994

Bacillus subtilis lon protease prevents inappropriate transcription of genes under the control of the sporulation transcription factor sigma G.

The Bacillus subtilis RNA polymerase sigma factor sigma G is a cell-type-specific regulatory protein that governs the transcription of genes that are expressed at an intermediate to late stage of sporulation in the forespore compartment of the sporangium. Here we report the identification of a mutation (lon-1) that causes inappropriate transcription of genes under the control of sigma G under nutritional and genetic conditions in which sporulation is prevented. The mutation is located at 245 degrees on the genetic map and lies within a newly identified open reading frame that is predicted to encode a homolog to Lon protease. Inappropriate transcription of sigma G-controlled genes in the lon-1 mutant is not prevented by mutations in genes that are normally required for the appearance of sigma G during sporulation but is prevented by a mutation in the structural gene (spoIIIG) for sigma G itself. In light of previous work showing that spoIIIG is subject to positive autoregulation, we propose that Lon protease is responsible (possibly by causing degradation of sigma G) for preventing sigma G-directed transcription of spoIIIG and hence the accumulation of sigma G in cells that are not undergoing sporulation. An integrated physical and genetic map is presented that encompasses 36 kb of uninterrupted DNA sequence from the lon pheA region of the chromosome, corresponding to 245 degrees to 239 degrees on the genetic map.

ATP-Dependent Proteases↗
PubMed1994

Assessment of cerebrovascular risk profiles in healthy persons: definition of research goals and the Austrian Stroke Prevention Study (ASPS).

The advent of new laboratory methods and noninvasive imaging modalities has extended the diagnostic possibilities in normal individuals. This article elaborates the new options for the assessment of stroke risk offered by these techniques. In this context we present the Austrian Stroke Prevention Study, which is the first prospective long-term investigation of normals that includes Doppler sonography, magnetic resonance imaging and single photon emission computed tomography. The design, utility and limitations of this study are discussed.

Aged↗
PubMed1994

Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome.

BACKGROUND AND PURPOSE: The aim of this study was to characterize the response of the hypothalamic-pituitary-adrenal system in the first hours of ischemic stroke and to relate its extent to the occurrence of acute confusional state, volume of brain damage, and clinical outcome. METHODS: The secretion of corticotropin (adrenocorticotropic hormone [ACTH]) and cortisol was studied in 23 patients by determinations at hours 4, 6, 8, 10, and 14 and days 1, 3, 5, and 7 after onset of symptoms. Acute confusional state (DSM-III-R criteria), extent of lesion (volumetry of computed tomographic scans), and neurological and functional outcome (Scandinavian Stroke Scale, Barthel Index scores) were assessed. RESULTS: The massive neuroendocrine response observed consisted of an initial phase with concomitantly increased levels of ACTH and cortisol and a second phase with decreased levels of ACTH while high concentrations of cortisol persisted. Initial levels of ACTH but not cortisol were significantly increased in patients with acute confusional state and significantly correlated with volume of brain lesion and neurological and functional outcome. CONCLUSIONS: An early and persisting activation of the hypothalamic-pituitary-adrenal axis was observed in relation to severity of disease. Its characteristic biphasic pattern suggests an initial central stimulation of release of ACTH followed by feedback suppression concomitant with an increased susceptibility of the adrenal gland. Because these hormones are known to exacerbate hypoxic injury to neurons, their massive release in hyperacute stroke may increase the extent of brain damage.

Acute Disease↗