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Biomedical subjects

G Holzer

Publications and source records attributed to G Holzer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Drug resistance against gemcitabine and topotecan mediated by constitutive hsp70 overexpression in vitro: implication of quercetin as sensitiser in chemotherapy.

Heat shock proteins have been reported to confer resistance to certain antineoplastic drugs. We investigated the impact of hsp70 overexpression on the efficacy of two new anti-cancer drugs, topotecan and gemcitabine. We used the fibrosarcoma WEHI-S cells stably transfected to overexpress the hsp70 cDNA from the constitutive SV40 promoter and appropriate control cells. After topotecan and gemcitabine treatment hsp70-overexpressing cells showed a marked elevation in cell survival, suggesting that hsp70 overexpression was sufficient to confer resistance to the drugs. In addition, hsp70-overexpressing cells were capable of starting cell proliferation after treatment with drug dosages that were lethal to control cells. Our results demonstrate that hsp70 overexpression represents a possible cause of drug resistance. In order to transfer these data to tumour cells constitutively expressing stress hsp70 due to the constitutive activity of the original hsp70 promoter we sought to supress the heat shock response pathway by the natural flavonoid quercetin, known to inactivate the heat shock transcription factor (HSF). Using a suitable cell line, we demonstrated the sensitising activity of quercetin. We found that antineoplastic drug concentrations exerting cytotoxic activity were markedly lower when cells were pretreated with quercetin. Concomitantly, hsp70 expression was strongly down-regulated under quercetin treatment. Our data indicate that quercetin may be useful as a sensitiser in chemotherapeutically treated patients suffering from hsp70-overexpressing tumours.

Animals↗
PubMed1995

Pattern of elevation of urine catecholamines in intracerebral haemorrhage.

Autonomic nervous system dysfunction is a common complication of severe intracranial disease. The aim of this study was to reveal the autonomic changes in patients suffering from acute intracerebral haemorrhage (ICH). 25 patients with spontaneous ICH within 24 hours of onset of symptoms were included. All patients were treated with standardised medical management and the meta- and normetanephrines were detected by high performance liquid chromatography (HPLC) in 24-hour urine every day. The mean level of normetanephrine (709 +/- 579 micrograms/day) and metanephrine (244 +/- 161 mg/day) were significantly elevated in comparison with a control group, p < or = 0.01. The norepinephrine elevation was of greater diagnostic and prognostic importance. Maximum urinary catecholamine metabolite levels occurred between day 3 to 10 after the bleeding. Normetanephrines correlated with the prognosis and the complications of ICH: intraventricular involvement resulted in significantly elevated normetanephrine levels (896 +/- 520 micrograms/day versus 311 +/- 78 micrograms/day) p < or = 0.01. Patients with a great volume of haematoma developed severe autonomic dysregulation (normetanephrines 1114 +/- 493 micrograms/day), whereas patients with smaller haematoma did not (339 +/- 125 micrograms/day) p < or = 0.0001; patients with bad outcome (1014 +/- 620 mg/day) had higher levels of normetanephrines than those with a good prognosis (322 +/- 110 micrograms/day) p < or = 0.001. A close relationship to elevated intracranial pressure was established. This study demonstrated the feasibility of detecting autonomic nervous system dysfunction in neurological intensive care patients by means of examination of the metabolites of the catecholamines in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Forearm bone density and grip strength in women after menopause, with and without estrogen replacement therapy.

Peaking in young adulthood, both bone mass and muscle strength decrease with ageing, but bone loss may accelerate after the menopause and can be delayed by estrogen replacement therapy (ERT). This study was designed to evaluate whether, like bone density, the muscle strength was affected by the onset of menopause and/or ERT. First grip strength (GS) of young female adults (group III; n = 18; age (+/- S.E.M.) 21.8 +/- 0.4 years) was compared to that of postmenopausal women, who were divided into two groups. Group I (n = 22; age 59.6 +/- 1.6 years) was 12.5 +/- 1.7 years after the menopause and received no ERT, and group II (n = 21; age 59.5 +/- 1.1 years) was 8.3 +/- 1.2 years after the menopause and had received ERT for 3.9 +/- 2.3 years at the time of the study. GS of the postmenopausal women was significantly (P < 0.005) lower than that of the young female adults. GS did not differ significantly between both postmenopausal groups. Further analysis revealed a weak negative correlation of years since menopause with forearm bone density (r = -0.37, P < or = 0.023 for group II and III together), but not with GS. It is concluded that the later onset of menopause and estrogen replacement therapy do not seem to have a noticeable influence on muscle strength.

Adult↗
PubMed1995

[Climacteric arthralgia and hand arthrosis].

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¿.

Aged↗
PubMed1994

The role of prolactin in the menopause.

Within a study on menopausal discomforts, 2322 women were seen for the first time at the Outpatients Department for Climacteric Disturbances and Prophylaxis of Osteoporosis at our clinic. Amongst routine hormonal examination we measured prolactin levels. We found hyperprolactinemia in 23 women. Furthermore, in 224 women who initially had normal hPRL values, an estrogen-gestagen replacement therapy was administered and within this we found a significant increase of the prolactin levels (P < 0.005). The role of prolactin in the climacteric period as well as the mechanism of the estrogen effect upon prolactin secretion are subjects of discussion.

Climacteric↗
PubMed1992

[Bone density before and after the hormonal therapy of young women with hypergonadotropic hypogonadal amenorrhea].

Dual energy X-ray absorptiometry of bone density in the lumbar vertebral column was performed in 32 young women (mean age 24.6 [19-34] years) with hypergonadotropic hypogonadal amenorrhoea. There was a significantly lower bone density (0.74 +/- 0.27 g/cm2) than in a control group of 27 women of similar age (1.17 +/- 0.081 g/cm2; P less than 0.001). Subsequently 21 of the 32 women received cyclical hormone substitution therapy for 24 months (day 1-30: 0.625 mg conjugated oestrogens; additionally, on days 20-30: 5 mg medrogestone; followed by a seven-day pause). After 6 months bone density, compared with that of the 11 untreated women, had increased significantly (P less than 0.001). It is therefore recommended that young hypoestrogenemic women should receive early and continuous hormone substitution treatment.

Absorptiometry, Photon↗
PubMed1992

Hypergonadotropic hypogonadic amenorrhea (World Health Organization III) and osteoporosis.

OBJECTIVE: To assess the bone mineral density in World Health Organization (WHO) III women after hormone replacement therapy. DESIGN: We studied the bone mineral density of 41 women with premature ovarian failure (hypergonadotropic hypogonadic amenorrhea--WHO III) before and during hormone replacement therapy. SETTING: All WHO III women were recruited from the Outpatient Department of the First Department of Gynecology and Obstetrics, University of Vienna Medical School, Austria, a public University Hospital. PATIENTS, PARTICIPANTS: Forty-one patients, 30 healthy women. INTERVENTIONS: Twenty-eight of 41 WHO III women received cyclic hormone replacement therapy consisting of 0.625 mg conjugated estrogen (days 1 to 30) and 5 mg medrogeston (days 20 to 30) in addition, with a 7-day interval. MAIN OUTCOME MEASURE: The bone mineral density was evaluated by single photon absorptiometry and dual energy x ray absorptiometry every 6 months (single photon absorptiometry six times, dual energy x ray absorptiometry four times). RESULTS: The bone mineral density in young women with hypergonadotropic hypogonadic amenorrhea (WHO III) was lower than in age-matched controls. Hormone replacement therapy produced an increase in bone mineral density in 28 WHO III women, whereas bone mineral density remained quite constant in the women without therapy. CONCLUSION: Hormone replacement therapy increases the bone mineral density of women with hypergonadotropic hypogonadic amenorrhea. Hormones should be substituted early and consistently in affected patients.

Adult↗
PubMed1992

[A main symptom of the climacteric manifestation complex: arthropathia climacteria].

In the last few years several studies have been published raising the question whether hormonal factors are co-responsible for the female prevalence of certain joint diseases. From our own clinical experience we know that more than half of the women seen at our outpatients department because of disorders of the post menopausal syndrome complain about arthralgies (especially of the PIP-joints). We have introduced the term "arthropathia climacterica" for it. Moreover the positive results of two clinical studies on which effects hormone replacement therapy had on these complaints indicate a relation between estrogens and joints.

Arthritis, Rheumatoid↗
PubMed1991

[Steroid hormone receptors in synovial tissue].

Among the variety of symptoms of the postmenopausal syndrome joint pain seems to be an important problem for the patient as well as for her doctor. Because of the excellent response of the hormone substitution therapy it is asked if the synovial membrane is a target organ for oestradiol. Biopsies from the knee joint of ten women (not having any hormone therapy)--excised during knee joint surgery--were examined. Only in two cases oestrogenreceptors were found. Accordingly the synovial membrane cannot be seen as a direct target organ for oestradiol and so other mechanisms must play a role in the pathogenesis of postmenopausal joint pain.

Adolescent↗
PubMed1990

Immunological differentiation between neuroborreliosis and multiple sclerosis.

Neuroborreliosis, a tick-borne spirochaetosis of the central nervous system, is diagnosed by the presence of intrathecally synthesized Borrelia burgdorferi-specific antibodies. Multiple sclerosis and neuroborreliosis can show similarities in clinical symptoms as well as lymphocytic cell reactions and oligoclonal bands in the isoelectric focusing of cerebrospinal fluid. To differentiate between multiple sclerosis and neuroborreliosis we tested intrathecally synthesized IgM and virus antibodies. The IgM indices were higher for most of the neuroborreliosis patients studied than for those with multiple sclerosis, and cell counts were also significantly higher in the acute stage of the disease. In 84% of multiple sclerosis patients we were able to demonstrate intrathecal antibody production against measles, rubella or mumps virus. Neuroborreliosis patients had no intrathecal virus antibody synthesis. The specification of oligoclonal bands resulting from isoelectric focusing of cerebrospinal fluid with an ELISA for B. burgdorferi can further substantiate the diagnosis of neuroborreliosis or help to rule it out in multiple sclerosis patients with positive borrelia-specific serology.

Adult↗
PubMed1990

Stimulation of beta 1-adrenoceptors enhances electrically evoked [3H]-acetylcholine release from rat phrenic nerve.

1. The effects of isoprenaline, noradrenaline and fenoterol on the electrically evoked release of [3H]-acetylcholine from the rat phrenic nerve were investigated. 2. Isoprenaline (0.1 mumol/L) and noradrenaline (1 mumol/L) enhanced evoked [3H]-acetylcholine release by about 90%, an effect which was abolished by CGP 20712A (0.1 mumol/L), a specific antagonist at beta 1-adrenoceptors. Noradrenaline still enhanced [3H]-acetylcholine release in the presence of phentolamine (1 mumol/L). 3. The enhancing effect of both isoprenaline and noradrenaline decreased at prolonged exposure times (24-32 min). A pre-exposure of the tissue to a low concentration (0.01 mumol/L) of isoprenaline prevented the enhancing effect of 0.1 mumol/L isoprenaline. 4. Fenoterol, a specific agonist at beta 2-adrenoceptors, did not modify evoked [3H]-acetylcholine release. 5. The present results indicate the existence of facilitatory beta 1-adrenoceptors on the motor nerve. These receptors appear to be desensitized either by a high concentration of, or by a long exposure to, agonists. Under the present conditions noradrenaline enhances the release of newly synthesized transmitter mainly by stimulation of beta-adrenoceptors.

Acetylcholine↗
PubMed1990

Cellular fatty acid compositions of an unidentified organism and a bacterium associated with cat scratch disease.

The cellular fatty acid composition of a gram-negative bacterium associated with cat scratch disease was determined by capillary gas chromatography-mass spectrometry (GC-MS). The fatty acid profile of this organism was distinct from those of other bacteria we have tested and was characterized by an unknown acid which was identified as 11-methyloctadec-12-enoic acid. The position of the branched methyl group in this acid was established by GC-MS of the reduced acid, and the location of the double bond was confirmed by GC-MS analysis of dimethyl disulfide derivatives. Another clinical isolate with no known relationship to cat scratch disease but with similar morphological and biochemical features had a similar fatty acid profile, including 11-methyloctadec-12-enoic acid.

Cat-Scratch Disease↗
PubMed1989

[Acute multifocal placoid pigment epitheliopathy with inflammatory CSF findings. A special form of borreliosis?].

A 24-year-old woman with acute multifocal placoid pigment epitheliopathy in both eyes had no signs or symptoms other than the impaired vision. Visual evoked potentials demonstrated prolonged latency. Lumbar CSF showed inflammatory changes. Serum antibody titres against Borrelia burgdorferi were markedly elevated. Cortisone treatment was without success, but intravenous penicillin quickly brought about improvement in vision. Borrelia infection may thus have been the cause of the multifocal placoid pigment epitheliopathy.

Acute Disease↗
PubMed1987

Capillary supercritical fluid chromatography of pyrrolizidine alkaloids.

The application of capillary supercritical fluid chromatography (SFC) for the separation of pyrrolizidine alkaloids (PAs) is examined. Most of these compounds are powerful toxins. Because they are present in at least 3% of all flowering plants, they are responsible for serious losses of livestock and human disease. Capillary SFC, with its high separation efficiency, is shown to be an excellent method for the chromatographic analysis of complex PA mixtures. Complete separation of the PAs of the retronecine and otonecine family has been achieved by pressure-programmed capillary SFC. The operating conditions are mild enough to prevent thermal decomposition of the alkaloids during analysis.

Carbon Dioxide↗
PubMed1984

Gas chromatographic analysis of volatiles in fluid and gas inclusions.

Most geological samples and some synthetic materials contain fluid inclusions. These inclusions preserve for us tiny samples of the liquid and/or the gas phase that was present during formation, although in some cases they may have undergone significant changes from the original material. Studies of the current composition of the inclusions provide data on both the original composition and the change since trapping. These conclusions are seldom larger than 1 millimeter in diameter. The composition varies from a single major compound (e.g., water) in a single phase to a very complex mixture in one or more phases. The concentration of some of the compounds present may be at trace levels. We present here some analyses of inclusion on a variety of geological samples, including diamonds. We used a sample crusher and a gas chromatography-mass spectrometry (GC-MS) system to analyze for organic and inorganic volatiles present as major to trace constituents in inclusions. The crusher is a hardened stainless-steel piston cylinder apparatus with tungsten carbide crushing surfaces, and is operated in a pure helium atmosphere at a controlled temperature. Samples ranging from 1 mg to 1 g were crushed and the released volatiles were analyzed using multi-chromatographic columns and detectors, including the sensitive helium ionization detector. Identification of the GC peaks was carried out by GC-MS. This combination of procedures has been shown to provide geochemically useful information on the processes involved in the history of the samples analyzed.

Aluminum Oxide↗