Biomedical subjects
Publications and source records attributed to J Huber.
A 56-year-old women who had undergone hysterectomy 15 years ago was found to have pulmonary leiomyomatosis. The occurrence of hormone receptors shows the influence of the ovary and of hormone-replacement-therapy to these tumors. In our case immunoperoxidase techniques indicate the expression of progesterone receptors.
In the present study the effect of oral contraceptive (OC) treatment on selected factors involved in the activation, i.e. circulating activated factor VII (cFVIIa), and in the inhibition of blood coagulation, i.e. plasma protein S activity and circulating thrombomodulin (cTM), were for the first time measured in OC users in a prospective study. Beside other coagulation variables, these parameters were measured during treatment with three low estrogen formulations containing different gestagen components (norgestimate, gestodene). During OC treatment increases in the activation markers prothrombin fragment F1 + 2 and D-Dimer were found, suggesting an increased activation of blood coagulation and fibrinolysis. Along with elevated plasma levels of FVII antigen, cFVIIa was also found increased in all three treatment groups, while inhibitory components of blood coagulation, plasma protein S activity and cTM, significantly and similarly decreased during treatment in all three treatment groups. We conclude that low dose estrogen pills induce similar changes in the plasma levels of main regulatory components of blood coagulation, despite differences in their gestagen components. Increased levels of activators and decreased activities of inhibitors may contribute to arterial and venous thrombotic complications seen in predisposed OC users.
The relations between 10 anthropometric variables describing the amount of adipose tissue and the serum levels of thyroxine, triiodothyronin, thyroid stimulating hormone, estradiol, progesterone, 17-hydroxyprogesterone, prolactin, luteinizing hormone, follicle stimulating hormone, DHEA-S, androstendion, testosterone, sex hormone binding globulin, growth hormone, IGF I as well as cortisol were investigated in 39 premenopausal and 38 postmenopausal women. Several statistically significant correlations between hormonal parameters and the amount and the distribution of subcutaneous fat tissue were found for the premenopausal group. The postmenopausal probands, however, showed fewer statistically significant connections between the two trait systems. The correlation patterns in both proband groups resembled each other. Only with regard to the gonadotropines (LH and FSH) a difference in the algebraic sign of the correlation coefficients can be observed for pre- and postmenopausal probands. The multiple regression analysis corroborated the hypothesis that hormonal parameters are responsible for somatic changes after menopause.
HIV-1 Rev protein directs nuclear export of pre-mRNAs and mRNAs containing its binding site, the Rev response element (RRE). To define how Rev acts, we used conjugates between bovine serum albumin (BSA) and peptides comprising the Rev activation domain (BSA-R). BSA-R inhibited Rev-mediated nuclear RNA export, whereas a mutant activation domain peptide conjugate did not. BSA-R did not affect the export of mRNA, tRNA, or ribosomal subunits, but did inhibit export of 5S rRNA and spliceosomal U snRNAs. BSA-R was itself exported from the nucleus in an active, saturable manner. Thus, the Rev activation domain constitutes a nuclear export signal that redirects RRE-containing viral RNAs to a non-mRNA export pathway.
After the co-infection of larvae of the lepidopteran Cryptophlebia leucotreta with the two baculoviruses C. leucotreta granulosis virus and Cydia pomonella granulosis virus (CIGV and CpGV, respectively), three CpGV mutants and one CIGV mutant carrying insertions of 0.9 to 4.7 kb have been isolated. By cloning, sequencing, and hybridization analysis, one of these insertions was identified as a transposon-like element derived from the C. leucotreta genome. This element, called TCl4.7, was found in the genome of CpGV which naturally replicates in C. pomonella. Sequence analysis suggested that TCl4.7 is 4726 bp in size, flanked by imperfect inverted terminal repeats of 29 bp, and integrated into the target dinucleotide TA. TCl4.7 encompasses an open reading frame sharing homologies to transposase genes of the Tc1-related transposable elements found in Caenorhabditis and in Drosophila species. The open reading frame might represent a pseudogene since it is missing an ATG start codon. The integration site of TCl4.7 is located in a non-protein-coding region of the CpGV genome at m.u. 9.5. In bioassays the TCl4.7-carrying virus and all the other mutants except for one showed LC50 values similar to those of CpGV and CIGV. This is the first report of the horizontal escape of a transposable element during the in vivo infection of lepidopteran larvae by granulosis viruses.
1. The organization of neuronal systems mediating presynaptic control of transmission from group II muscle afferent fibres has been investigated by comparing the sources of presynaptic inhibition of fibres terminating in different segments of the spinal cord: fibres of the semitendinosus and lateral gastrocnemius muscle nerves terminating in the sacral segments and of the tibialis anterior and extensor digitorum longus muscle nerves terminating in the midlumbar segments. 2. Two measures of presynaptic inhibition were used: depolarization of the terminals of group II fibres (detected as changes in the excitability of single fibres to electrical stimuli) and a decrease in the effectiveness of their synaptic actions (detected as a decrease in the amplitude of monosynaptic field potentials evoked by group II muscle afferents). 3. Group II muscle afferents strongly depolarized all of the group II afferent fibres, while group I muscle afferents contributed to the depolarization of only a few. The majority of fibres were as effectively depolarized by cutaneous afferents as by the most effective muscle afferents. However, the effectiveness with which afferents of different nerves depolarized group II muscle afferent fibres in the sacral and midlumbar segments differed. The most effective afferents were those of nerves that provide the main input to dorsal horn interneurones in the same region of the spinal cord. The sources of depolarization of flexor and extensor fibres terminating in the same (sacral) segments were very similar. 4. The amplitudes of field potentials evoked by group II afferents were depressed by the same types of afferent as produced depolarization of group II afferent fibres. There was also a strong correlation between the effectiveness with which afferents of a given nerve induced depolarization of single fibres and depression of field potentials in the same segments. Since group II field potentials were depressed to a greater extent (by up to 90%) than group I field potentials (by no more than 20%) concurrently recorded in the intermediate zone of midlumbar segments, it appears that transmission from group II muscle afferents may be more strongly affected by presynaptic inhibition than that from group I muscle afferents. 5. The results suggest that the interneuronal systems responsible for the presynaptic control of transmission from group II muscle afferents have topographically restricted actions and an organization appropriate to a system of negative feedback control.
In a double-blind, placebo-controlled study, the antidepressant and vigilance-promoting properties of transdermal oestrogen in post-menopausal depression were investigated utilizing hormonal, syndromal and EEG mapping evaluations. Sixty-nine menopausal women, aged 45-60 years without previous hormonal replacement therapy, diagnosed as major depression without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [Estraderm TTS (ETTS) 50 micrograms, applied twice weekly] or placebo. No other psychoactive medication was allowed. After removal of protocol violators, 32 patients were evaluable in each group, which did not differ in age, height or weight. As five patients discontinued prematurely in both groups and in one placebo patient a post-drug EEG could not be obtained, 27 patients remained in the ETTS and 26 in the placebo group for efficacy analysis. While in the placebo group, oestradiol (E2) and follicle stimulating hormone (FSH) remained unchanged, E2 increased and FSH decreased significantly in the ETTS group. Syndromal evaluation showed a significant improvement in the Kupperman Index (KI) as well as Hamilton Depression Rating Scale (HAMD) in both groups, with no inter-group difference. However, EEG mapping demonstrated significant inter-drug differences in brain function, mostly over the left temporal region. While ETTS patients showed an increase of alpha and alpha-adjacent theta activity and a decrease of beta activity, as well as an acceleration of the delta/theta centroid and a slowing of the alpha, beta and total power centroid, no changes occurred in the placebo-treated patients. These neurophysiological findings suggest improvement of vigilance by oestrogen, previously referred to as "mental tonic" effect. There were no changes, however, in the frontal alpha asymmetry index, reflecting left frontal hypo- and right frontal hyperactivation. Thus, this neurophysiological variable represents a state-independent marker for depression. The tolerability of ETTS was very good.
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Lowering the total steroid dose in modern oral contraceptives (OCs) has been connected with a higher incidence of ovarian follicle and cyst formation. To investigate the presence of ovarian follicles and cysts by means of vaginal ultrasonography and serum hormone determinations during use of two low-dose OCs, 65 volunteers were randomized to receive either 20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel (group A) or 35 micrograms EE + 250 micrograms norgestimate (group B) for a 2-month study period. At baseline, 39% of women in group A and 31% in group B exhibited at least one follicle < 35 mm in diameter. By the end of the second treatment cycle, the frequency of these follicles had decreased to 14% in each group. Only one subject in the higher estrogen group developed an ovarian cyst > 35 mm. One subject in each group demonstrated hormone levels characteristic of ovulation; no pregnancy occurred in either group. The 20 micrograms EE preparation was not found to lead more often to ovarian follicles or cysts when compared with a 35 micrograms EE preparation, possibly because of the type and dose of the progestogen used.
A manual non-radioactive DNA sequencing protocol was developed for rapid analysis of variable HIV-1 genomes. Sets of up to ten primers were used in one sequencing reaction. After polyacrylamide gel electrophoresis and blotting onto nylon membranes the individual sequences were detected by hybridization with digoxigenin-labelled oligonucleotides and chemiluminescence. The method is applicable to any sequencing project where numerous variants of DNA fragments of several 1000 bp of length are to be analysed.
To assess the function of the hypothalamic-pituitary-gonadal (HPG) axis in major depression, a multihormonal study was carried out in 20 depressed premenopausal women. Serum concentrations of LH, FSH, estradiol, progesterone, testosterone, and GnRH-stimulated LH and FSH were measured before initiation of treatment (on the first day after menstruation) and during clomipramine treatment (same time one menstrual cycle later). Significantly higher blood concentrations of testosterone were found in untreated patients compared to normal controls. Furthermore, there was a significant negative correlation between Hamilton depression scores and estradiol concentrations of patients. The efficacy of clomipramine treatment was not related to hormonal parameters.
The aim of our study was to examine the effects of hormone replacement on the size of the uterus and the development or increase of myomatas. Fifty perimenopausal women were included in the study (53.8 +/- 5.0 years). Patients received a substitution therapy composed of a combination of 4 mg estradiovalerate and 200 mg prasteronenantate (Gynodian Depot cartridges) given as a muscular injection in 6-10 week intervals (mean 7 weeks +/- 4 days). Prior to the onset of therapy with Gynodian and after a period of 12 months (+/- 13 days) vaginosonography was performed. Measurements taken were length, thickness, height of endometrium, size of ovaries and of myomas. Data obtained were correlated with baseline findings. Within 1 year, significant increases in uterus length from 73.4 mm to 88.2 mm, in uterus thickness from 33.9 mm to 43.5 mm and in endometrium height from 4.1 mm to 6.7 mm were observed (median values). There was an increase in both the number (from 2.2 to 3.5) and the size of the myomatas (29.4-35.0 mm diameter). A statistical analysis conducted by means of the Wilcoxon matched pairs signed-rank sum test showed P < 0.001. No significant change occurred in the size of the ovaries. Our study shows that hormone substitution may have an impact on uterus growth and that therefore vaginosonographical monitoring can be recommended.
OBJECTIVES: The aim of the present study was to investigate the influence of a continuous estrogen, cyclic progesterone replacement therapy on the secretion of growth hormone (GH) and IGF I as well as of somatometric-GH correlation patterns. METHODS: The study included 23 healthy postmenopausal women. Of the proband group 13 randomly selected women were treated with orally applicated 2 mg estradiol-valerat (E2V) and 10 mg dydrogesterone for 10 months. Ten women did not receive any hormonal treatment during this time. After 10 months all probands were reexamined and their GH and IGF I secretion, as well as their somatometric-hormonal correlation patterns, compared with those of a fertile control group. RESULTS: It could be shown, that in postmenopausal women a 10-month oral hormone replacement therapy led to a significant increase of GH- and IGF I levels, however, the treated postmenopausal women did not reach the levels of the fertile controls. Those women who did not receive any hormonal treatment and the postmenopausal women before HRT showed nearly identical GH- and IGF I levels as well as somatometric-GH correlation patterns. CONCLUSIONS: The results of the present paper indicate a marked influence of estrogens on GH and IGF I secretion. Furthermore, hormonal replacement therapy (HRT) may influence somatometric GH correlation patterns too.
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This study aimed at a possible classification of climacteric arthroses of the hand. 132 females suffering from arthralgias of the wrist and finger joints who had consulted our outpatient department originally because of climacteric complaints, were examined while asking them to complete a questionnaire with clinical criteria for classifying arthroses of the hand. The requisite number of criteria required for classification as ¿arthrosis of the hand¿ were attained in all three groups of females (premenopausal and postmenopausal women without operation, as well as hysterectomised and/or ovarectomised women¿, although the ex-ray showed no signs of degenerative arthritis. The subjective complaints voiced by the patients are opposed to the x-ray finding, so that it is not permissible to classify climacteric arthralgias of the wrist and finger joints as ¿arthritis¿.
The Hu antigens are composed of a family of neuronal-specific, RNA-binding proteins encoded by at least three distinct genes. All three gene products, HuD, HuC/ple21, and Hel-N1, are human homologues of Elav, a Drosophila protein required for neuronal development and maintenance. Although the three proteins are very similar in structure, they are differentiated by alternative splicing of their mRNAs. We report here that the Hu antigens bind avidly to the AU-rich element resident in many mRNAs that regulate cell proliferation. This interaction suggests that the Hu antigens promote neuronal differentiation by suppressing the neuroblast cell cycle. Such a mechanism provides a plausible model for the role of the Hu antigens in tumorigenesis, neuronal differentiation, and paraneoplastic neurologic disorders.
Growth promoting activity (GPA) is a chick growth factor with low homology to mammalian ciliary neurotrophic factor (CNTF) (47% sequence identity with rat CNTF) but displays similar biological effects on neuronal development. We have isolated a chick cDNA coding for GPA receptor (GPAR alpha), a GPI-anchored protein that is 70% identical to hCNTFR alpha. Functional analysis revealed that GPAR alpha mediates several biological effects of both GPA and CNTF. Soluble GPAR alpha supports GPA- and CNTF-dependent survival of human TF-1 cells. In sympathetic neurons, GPAR alpha mediates effects of both GPA and CNTF on the expression of vasoactive intestinal peptide (VIP) as shown by the inhibition of GPA- and CNTF-mediated VIP induction upon GPAR alpha antisense RNA expression. These results demonstrate that GPAR alpha is able to mediate effects of two neurokines that are only distantly related. GPAR alpha mRNA expression is largely restricted to the nervous system and was detected in all neurons that have been shown to respond to GPA or CNTF by increased survival or differentiation, i.e. ciliary, sympathetic, sensory dorsal root, motoneurons, retinal ganglion cells and amacrine cells. Interestingly, GPAR alpha mRNA was additionally found in neuronal populations and at developmental periods not known to be influenced by GPA or CNTF, suggesting novel functions for GPAR alpha and its ligands during neurogenesis and neuron differentiation.
The creep and wear behaviour of pressed UHMWPE and extruded UHMWPE was compared, taking Chirulen and extruded UHMWPE of the Lennite type as examples. Using the ring-on-disc test, the wear and deformation volumes per 360,000 cycles were determined. The static tests were performed at surface pressures of 5.62 MPa and 9.37 MPa, while the test duration was 41.86 and 100 hours, respectively. The surface pressures result from the axial forces of 900 N and 1500 N, respectively, and a ring surface analogous to the DIN 58,835 and ISO 6474 standards. Between conventionally pressed and the extruded UHMWPE material differences of up to 350% in the sums of wear and deformation were found. It was noted that already at low surface pressures the extruded UHMWPE is more susceptible to creep deformation than is the conventionally pressed material, and that this effect dramatically increases at high surface pressures.