Changes in student characteristics.
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Biomedical subjects
Publications and source records attributed to G Gross.
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The cause of condylomata acuminata and of other anogenitally located HPV lesions in children often remains undetermined. Sexual abuse is a possible cause of HPV infection in childhood. Non-venereal transmission of HPV, such as autoinoculation and heteroinoculation from extragenital sites to genitalia, however, is much more likely in this age group. Histology and HPV typing of genital warts may provide evidence for non-venereal transmission of HPV in children. Identification of the genital HPV types HPV 6, 11, 16, 18, 31, etc. in a child is no proof of sexual abuse. Behavioural abnormalities and a carefully elicited history aid clinicians in coming to reliable conclusions and in deciding whether an HPV infection in a child is sexually transmitted and due to sexual abuse.
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Chimeric transcripts containing the ribosome binding site of the Escherichia coli atpE gene and variants of the human structural interferon-beta gene are subject to RNase E processing in the 5'-untranslated atpE part of the transcripts. The absence of processing at two sites in the atpE leader-sequence caused by the RNase E deficiency in E. coli host N3431 leads to a considerable stabilization of the mRNA moiety. RNase E has originally been described as a processing enzyme for non-mRNAs such as precursor 5 S rRNA and RNA1, but cleavage mRNA substrates have also been reported. RNase E processing of the atpE gene leader sequence-containing transcripts leads to an increased rate of mRNA breakdown. The two RNase E-dependent processing sites in the atpE part of the mRNA transcripts exhibit some similarity to the other known RNase E processing sites. The influence of RNase E cleavage upon post-transcriptional regulation such as RNA stability and the efficiency of translational initiation is discussed.
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The effects of neuropeptide Y (NPY), peptide YY (PYY), pancreatic polypeptide and of another four peptides on the electrically evoked 3H overflow were studied in superfused rat brain cortex slices preincubated with 3H-serotonin. In addition, we determined the effect of NPY on the Ca2(+)-induced 3H overflow from rat brain cortex slices and synaptosomes (preincubated with 3H-serotonin) and on the forskolin-stimulated accumulation of cAMP in a membrane fraction from rat brain cortex. The electrically (3 Hz) evoked 3H overflow was inhibited by PYY, NPY and pancreatic polypeptide (decreasing order of potency), but not affected by ACTH1-24, angiotensin II, bradykinin and delta-sleep-inducing peptide. The inhibitory effect of NPY did not change when the stimulation frequency was lowered to 1 Hz, but was markedly reduced at 10 Hz. The inhibitory effect of a presumably maximally active concentration of PYY was not altered in the presence of NPY or pancreatic polypeptide (effects not additive), whereas the inhibition produced by a maximally active concentration of the alpha 2-adrenoceptor agonist clonidine was further increased by NPY. NPY also inhibited (1) the tritium overflow, evoked by introduction of Ca2+, in slices superfused with Ca2(+)-free and K(+)-rich medium containing tetrodotoxin, (2) the tritium overflow, evoked by simultaneously increasing Ca2+ and K+ in the superfusion fluid of synaptosomes previously superfused with Ca2(+)-free medium and (3) the forskolin-stimulated accumulation of cAMP in rat brain cortex membranes. The present results suggest that NPY inhibits serotonin release in the rat brain via presynaptic NPY receptors, which are also activated by PYY and pancreatic polypeptide and may be negatively coupled to an adenylate cyclase.
In a study of 17 patients with malignant melanomas in the extremities the sensitivity and specificity of a new monoclonal antibody directed at melanoma cells (BW 575, Behring) were investigated. The specificity was 100%, but the sensitivity 70%. In 3 cases known foci could not be detected. All nodular melanomas and their metastases were detected (9 patients). Repeated examination during the first 24 h after injection of the Tc-99m-marked antibody, and two-plane investigations made it possible to detect even small tumors less than 1 cm in diameter and subcutaneous lesions where the melanomas absorbed the antibodies. Due to its high specificity, the antibody seems to be a promising aid in deciding the operative strategy.
Trimipramine has been reported to differ from other typical tricyclic antidepressant drugs in several aspects, for instance it does not inhibit neuronal transmitter uptake and does not cause down-regulation of beta-adrenoceptors. Moreover, it may possess antipsychotic activity in schizophrenic patients. In the present investigation it was found that trimipramine did not alter the electrically-induced release of [3H]noradrenaline and [3H]5-hydroxytryptamine, from slices of the cerebral cortex of the rat, in concentrations of less than 1 microM. It did not antagonize the inhibitory effect of noradrenaline and 5-hydroxytryptamine on the release of transmitter, mediated by presynaptic autoreceptors. In radioligand binding studies, D,L-trimipramine showed fairly high affinities (KI 10-60 nM) for some dopamine (DA), noradrenaline and 5-hydroxytryptamine (5-HT) receptor subtypes (5-HT2 receptors = alpha 1A/B-adrenoceptors greater than or equal to D2 receptors), intermediate affinities (300-550 nM) for D1 receptors, alpha 2B-adrenoceptors and 5-HT1C receptors but only low affinities (greater than 1000 nM) for alpha 2A-adrenoceptors, 5-HT1A, 5-HT1D and 5-HT3 receptors. It may thus be classified as an atypical neuroleptic drug. Especially, its affinities for dopamine receptors, alpha 1-adrenoceptors and 5-HT2 receptors closely resembled the values measured for clozapine. The L-enantiomer of trimipramine showed higher affinities for these binding sites than D-trimipramine. The present findings may explain the mechanism of the potential antipsychotic action but not the antidepressant effect of trimipramine.
The distributions of the alpha 1-adrenoceptor and its subtypes (alpha 1A and alpha 1B) in human and rat hippocampus are analysed by quantitative receptor autoradiography. alpha 1-Adrenoceptors are labelled by [3H]prazosin. The alpha 1A subtype is visualized by [3H]prazosin after irreversible blockade of alpha 1B adrenoceptors with chloroethylclonidine or directly by [3H]5-methyl-urapidil. The alpha 1B subtype is investigated by [3H]prazosin binding in the presence of the alpha 1A antagonist 5-methyl-urapidil. Considerable differences in the regional and laminar patterns of alpha 1-adrenoceptors are found between rat and human hippocampi. The rat hippocampus is characterized by a low overall density and a rather homogeneous regional and laminar distribution. This is in contrast to the human pattern, which shows a much higher overall level of alpha 1 receptor density and a restriction of alpha 1 receptors to the CA3 region of Ammon's horn and the dentate gyrus. Moreover, alpha 1A and alpha 1B receptors of the human hippocampus are differentially distributed with the alpha 1A subtype concentrated in the hilus and lucidum layer of CA3, and the alpha 1B subtype concentrated in the molecular layer of the dentate gyrus. Additionally, the distribution of alpha 1 receptors is compared with the distribution of 5-hydroxytryptamine 1A receptors. The subtype specific pattern is correlated with the distribution of glutamatergic systems in the human (but not in the rat) hippocampus. alpha 1A Receptor localization coincides with the target area of the mossy fibre system, and alpha 1B receptors are preferentially localized in the target area of the hippocampal associational fibres and partly of the perforant pathway. This result points to possible interactions between noradrenaline- and glutamate-mediated neurotransmission differentiated by topographically segregated alpha 1-adrenoceptor subtypes.
The distribution of 12 different binding sites for acetylcholine, L-glutamate, GABA, 5-hydroxytryptamine, dopamine and noradrenaline was measured with quantitative receptor autoradiography in four regions of the rat basal forebrain (medial septal nucleus including vertical and horizontal limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata and basal nucleus of Meynert, ventral pallidum). L-Glutamate binding sites represent the largest portion of the analysed receptors in all regions, followed by muscarinic2, 5-hydroxytryptamine1 and GABAA receptors. Muscarinic1, dopamine1, dopamine2 and 5-hydroxytryptamine2 receptors and alpha 1-, alpha 1A- and alpha 1B-adrenoceptors represent the minor receptor populations. The largest portion of the dopamine receptors is represented by the dopamine1 subtype, and the alpha 1B subtype dominates the alpha 1-adrenoceptor group. A heterogeneity of the distribution patterns of the different receptors throughout the basal forebrain regions is found. A comparison of the patterns shows that alpha 1-adrenoceptors have a similar regional distribution to that of the muscarinic2 receptors, but both receptor types have reciprocal distributions compared with the 5-hydroxytryptamine1 receptors. The results indicate that one transmitter may exert different effects in the basal forebrain regions depending on the densities of the respective receptor subtypes. Moreover, similar or reciprocal distribution patterns of some, but not all, analysed receptors point to a non-random association (co-distribution) of the different transmitter systems in the basal forebrain regions.
Transporting radioactive materials within a medical complex comes under jurisdiction of the U.S. Department of Transportation when public highways are used. A strong, reusable container to safely transport radioactive material was developed and tested at Mayo Medical Center to satisfy the requirements of the U.S. Department of Transportation and Nuclear Regulatory Commission. The container successfully completed water spray, free drop, compression, and penetration tests. It has been in use for 3 y without any loss of radioactive materials.
The case of a 22-year-old man suffering from genital warts is described. The lesions responded completely to recombinant interferon alfa-2a only after discontinuation of cannabis consumption. Cannabis was detected using the enzyme immunoassay/1-trans-tetrahydrocannabinoid method in urine. Southern blotting of frozen genital wart biopsy material revealed papillomavirus type 11 DNA, the amount of which increased significantly during interferon treatment. The final clearing of lesions after discontinuation of cannabis consumption implicates that the drug-induced impairment of cellular immunity was reversible. It is concluded that drug abuse and especially cannabis consumption may play some role in the world-wide increase in genital papillomavirus disease and in the high number of recalcitrant courses of genital warts.
The question of determining prognostically relevant features for schizophrenia was approached with multivariate statistical methods applied to the data from the Bonn longitudinal study of 502 schizophrenic patients. In this study, personal interviews according to a clinical classification scheme allowed every patient to be ranked within each of three different outcome classes: psychopathological remission, occupational remission, and course type. Our multivariate analysis encompassed a total of 50 items pertinent to the time up to and including the first 6 months after the first psychotic manifestation. Despite the introduction of mathematical methods considerably more sophisticated than those employed in earlier studies, no satisfactory solution could be found to the problem of predicting end states of schizophrenia. Reliable predictions could be made only for 'extreme' end states (i.e. full remission versus (1) characteristic residues in the narrower sense; (2) total unemployment, or (3) surging or simple courses to mixed residues or to typical schizophrenic defect psychoses). Accordingly, sufficiently reliable assertions applied only to a minority of about 1/3 of patients, whereas for the majority of 2/3, no generalizable prognostication was possible (67-71% true-positive predictions on 36-63% of total population in extreme states). By contrast, our analyses have clearly uncovered a fundamental problem of investigations into the long-term prognosis of schizophrenia: the extreme dependence of results on the clinical definition of end states. The further the phenomenon 'end state' is qualitatively subdivided, the poorer and less reproducible is the mutual discrimination between intermediate states and the less reliable are allocations of patients to these intermediate states by means of multivariate classifiers. Furthermore, our analyses have also demonstrated the usefulness of multivariate, adaptive procedures for investigations into the structural properties of long-term courses, so that predictions might be considerably improved if more reliable definitions of schizophrenic end states are available.
In rat ventricular myocytes, the effects of alpha adrenoceptor stimulation on outward currents were studied by means of the whole cell voltage-clamp technique. Phenylephrine (30 microM) in the presence of propranolol (1 microM) to block beta adrenoceptors reduced voltage-activated transient outward current. Both components of transient outward current were affected, i.e., peak current (Ipeak) was reduced by 25.3 +/- 1.8%, the outward current at the end of a clamp step (Ilate) was reduced by 39.1 +/- 3.5% (n = 5; holding potential -40 mV, clamp step to +20 mV). In order to describe the alpha-1 adrenoceptor subtypes involved in this action, the effect of phenylephrine was also investigated after pretreatment of the cells with various antagonists. Pretreatment with prazosin (0.3 microM) abolished completely the phenylephrine effect. The alpha-1A adrenoceptor subtype-selective antagonists 5-methylurapidil and (+)-niguldipine (0.1 microM each) and the irreversible alpha-1B adrenoceptor subtype antagonist chloroethyl-clonidine (100 microM) blocked the phenylephrine effect on Ipeak, but merely attenuated the effect on Ilate, whereas pretreatment with a combination of chloroethylclonidine and (+)-niguldipine suppressed the phenylephrine-induced effect on both outward current components just like prazosin did. In conclusion, stimulation of both adrenoceptor subtypes is required for reduction of Ipeak, but stimulation of either alpha-1A or alpha-1B subtype is sufficient for reduction of Ilate. Therefore, stimulation of both alpha-1 adrenoceptor subtypes contributes to the phenylephrine-induced reduction in transient outward currents of isolated rat myocytes.
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In this review the traditional concepts of endogenous depression and modern trials of classification in operationalized diagnostic systems, especially in DSM and ICD, are critically discussed. The psychopathological and other phenomenological symptomatologies of endogenous (cyclothymic) depression within monopolar and bipolar affective psychoses and the diagnosis and differential diagnosis above all against schizophrenia, organic brain diseases and psychoreactive disorders, are described. The possibilities and limitations of operationalized classifications with regard to diagnostic reliability and validity are presented. At present state of research homogeneous groups of patients with regard to affective and other idiopathic psychoses and here depressive syndromes and episodes cannot be defined, neither with the traditional concepts nor with the up to now available operationalized diagnostic classifications. In contemporary operationalized diagnostic systems among others the psychopathological and other phenomenological criteria are not sufficiently or too vaguely defined, the different significance of the requested inclusion-criteria and the intraindividual variability with regard to single episodes and subsequent phases of the depression are too little considered. Up to now all trials failed to validate different diagnostic concepts of depression by biological markers. Clinical psychopathological diagnosis of endogenous depression according to the traditional psychiatry criteria may reach a better validity under certain conditions than diagnoses according to DSM-III-R or ICD 10. To use exclusively operationalized diagnostic systems instead of clinical diagnosis in the diagnostic practice but also in research would be too early at present. Modern diagnostic systems can complete the clinical diagnosis but not replace it.
Efficient expression in Escherichia coli (E. coli) of the human interferon-beta gene (IFN-beta) gene and of a chemically synthesized IFN-beta gene variant (506 base pairs; synIFN-beta) adapted to the E. coli codon usage, both fused to the E. coli atpE ribosome-binding site, is controlled either by primary sequence or by mRNA secondary-structure in the translational initiation region. High level expression of the natural human atpE/IFN-beta gene fusion is governed by the nucleotide composition preceding the initiator codon AUG. A single U----C exchange in the -2 or -1 position preceding the initiator codon AUG reduces the translational efficiency from 18% of total cellular protein to only 8% or 4%, respectively, while both U----C substitutions reduce IFN-beta expression below 1%. These sequence alterations interfere with efficient ribosome binding as revealed by toeprinting. They provide further evidence for the influence of the anticodon-flanking regions of tRNA(fMet) upon the initiation rate of translation. In contrast, translation of the synthetic variant atpE/synIFN-beta gene fusion is controlled by a moderately stable stem-loop structure (delta G = -4 kcal/mol; 37 degrees C) located within the coding region and overlapping the 30 S ribosomal subunit attachment site. That the stability of the hairpin interferes with the initiation of translation is inferred from site-directed mutagenesis and toeprint analyses. mRNA half-life in these variants is positively correlated with the rate of translation and involves two major endonucleolytic cleavage site 5'-upstream of the Shine-Dalgarno region.
To assess the performance of FLAG and RSE NMR angiography 22 aortoiliac (AI) and 22 femoropopliteal (FP) angiograms in 11 healthy males, mean age 38 +/- 7.6 years, were acquired. The image quality was graded in a blinded fashion by two independent readers. The readers grades were not statistically different (kappa = 0.5696). The representation of diagnostic images was 6/11 FLAG and 8/11 RSE AI as well as 8/11 FLAG and 8/11 RSE FP. On back-to-back comparison six RSE AI and seven RSE FP were graded better than their FLAG counterparts. Although these differences did not achieve a statistical significance RSE NMR angiography provided consistently better images and appears preferable for imaging of the peripheral vascular system in normal subjects.