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Biomedical subjects

A Honig

Publications and source records attributed to A Honig.

At least 19 recordsLinked to original sources
PubMed2007

Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation.

LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration. In the present work, we analysed the effect of LASP-1 on biology and function of human ovarian cancer cell line SKOV-3 using small interfering RNA technique (siRNA). Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in SKOV-3 cells. The siRNA-treated cells were arrested in G(2)/M phase of the cell cycle and proliferation of the tumour cells was suppressed by 60-90% corresponding to around 70% of the cells being transfected successfully as seen by immunofluorescence. Moreover, transfected tumour cells showed a 40% reduced migration. LASP-1 silencing is accompanied by a reduced binding of the LASP-1-binding partner zyxin to focal contacts without changes in actin stress fibre and microtubule organisation or focal adhesion morphology as observed by immunofluorescence. In contrast, silencing of zyxin is not influencing cell migration and had neither influence on LASP-1 expression nor actin cytoskeleton and focal contact morphology suggesting that LASP-1 is necessary and sufficient for recruiting zyxin to focal contacts. The data provide evidence for an essential role of LASP-1 in tumour cell growth and migration, possibly through influencing zyxin localization.

Adaptor Proteins, Signal Transducing↗
PubMed2007

Altered omega-3 polyunsaturated fatty acid status in depressed post-myocardial infarction patients.

OBJECTIVE: Lower levels of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFAs) and increased inflammation have been associated with both depressive disorder and myocardial infarction (MI). The present study investigated whether patients who develop depression post-MI, have higher arachidonic acid/eicosapentanoic acid (AA/EPA) ratios than non-depressed post-MI patients and whether depressed post-MI patients have signs of increased inflammation as measured by C-reactive protein (CRP). METHOD: Serum AA/EPA ratio and plasma CRP levels were quantified in 50 post-MI patients, of which 29 were depressed and 21 non-depressed. RESULTS: Compared with the non-depressed group, depressed post-MI patients had significantly higher AA/EPA ratios. No significant difference was observed in CRP levels. CONCLUSION: Depressed post-MI patients had lower levels of n-3 LCPUFAs as measured by mean AA/EPA ratio and no signs of increased inflammation as determined by CRP levels.

Adult↗
PubMed2006

Increased tartrate-resistant acid phosphatase (TRAP) expression in malignant breast, ovarian and melanoma tissue: an investigational study.

BACKGROUND: Tartrate-resistant acid phosphatase (TRAP) is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. METHODS: TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. RESULTS: A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. CONCLUSION: Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.

Acid Phosphatase↗
PubMed2006

Radon activity concentration--a Euromet and BIPM supplementary comparison.

For the first time, a comparison of radon activity concentration in air has been performed within the scope of Euromet. In the project 657, 'Comparison of calibration facilities for the radon activity concentration,' 12 participants from 9 countries compared different radon reference atmospheres at 1, 3 and 10 k Bq m-3 via a transfer standard. The comparison was listed as BIPM supplementary comparison EUROMET.RI(II)-S1. The results of most participants are correlated due to common traceability to one single radon gas standard producer. This makes a careful correlation analysis necessary to achieve an appropriate comparison reference value. The results of the comparison as well as the complex analysis of the correlated set of data is presented and discussed.

Air Pollutants, Radioactive↗
PubMed2006

[Psychiatric disorders in pregnant and puerperal women].

The most frequently occurring pre- and postpartum psychiatric disorders are depression and, to a lesser degree, panic disorder and psychosis. Apart from the negative effects on the psychological well-being of the mother, these psychiatric disorders may also result in obstetric complications and an impaired mother-infant relationship. In order to prevent these negative effects, mothers who are at risk for major psychiatric disorders need to be identified early, preferably before or during pregnancy. The most important risk factor is a history of psychiatric disorders. Obstetric risk factors for depression are unplanned or unwanted pregnancy, pregnancy-related hypertension, emergency caesarean section and early discharge from the hospital. Other factors are low socioeconomic status, recent life event, negative self-image, little social support, immigration in the last 5 years, feelings of loss of control during pregnancy and feeding problems with the child. For treatment, pregnant or puerperal women with a possible psychiatric disorder based on the presence of a serious risk factor, such as a previously experienced psychiatric disorder (related to pregnancy or not), serious current psychiatric symptoms or long-time use of psychoactive drugs, should be referred preferably to a combined psychiatric/obstetric clinic or, if unavailable, to a psychiatrist in a general hospital.

Adult↗
PubMed2006

Focal or generalized vascular brain damage and vulnerability to depression after stroke: a 1-year prospective follow-up study.

BACKGROUND: Both the lesion location hypothesis and the vascular depression hypothesis have been proposed to explain the high incidence of depression in stroke patients. However, research studying both hypotheses in a single cohort is, at present, scarce. OBJECTIVE: To test the independent effects of lesion location (left hemisphere, anterior region) and of co-occurring generalized vascular damage on the development of depression in the first year after ischemic stroke, while other risk factors for depression are controlled for. METHODS: One hundred and ninety consecutive patients with a first-ever, supratentorial infarct were followed up for one year. CT was performed in the acute phase of stroke, while in 75 patients an additional MRI scan was also available. Depression was assessed at 1, 3, 6, 9, and 12 months after stroke using self-rating scales as screening tools and the SCID-I to diagnose depression according to DSM-IV criteria. RESULTS: Separate analyses of the lesion location hypothesis and the vascular depression hypothesis failed to reveal significant support for either of these biological models of post-stroke depression. Similar negative results appeared from one overall, multivariate analysis including variables of both focal and generalized vascular brain damage, as well as other non-cerebral risk factors. In addition, level of handicap and neuroticism were independent predictors of depression in this cohort, as has been reported previously. CONCLUSION: This study supports neither the lesion location nor the vascular depression hypothesis of post-stroke depression. A biopsychosocial model including both premorbid (prior to stroke) vulnerability factors, such as neuroticism and (family) history of depression, as well as post-stroke stressors, such as level of handicap, may be more appropriate and deserves further study.

Aged↗
PubMed2005

The effects of an acute serotonergic challenge on brain-gut responses in irritable bowel syndrome patients and controls.

BACKGROUND: Serotonin, a key denominator of the brain-gut axis is involved in the regulation of gastrointestinal function as well as cognition, mood and hypothalamic-pituitary-adrenal axis-mediated neuroendocrine responses. AIM: To assess the effects of an acutely increased serotonergic activity, using a 20 mg intravenous citalopram challenge test on visceral perception, affective memory performance, mood and neuroendocrine responses, respectively, in diarrhoea-predominant irritable bowel syndrome patients and controls. METHODS: In a randomized, double-blind crossover design, 14 diarrhoea-predominant irritable bowel syndrome patients and 14 matched controls were studied under citalopram and placebo conditions, respectively. Visceral perception was scored in response to rectal distensions. Affective memory performance, mood, levels of adrenocorticotropic hormone, cortisol, prolactin and biochemical parameters of serotonergic metabolism were simultaneously assessed. RESULTS: Visceral perception did not significantly differ between the citalopram and placebo condition. Citalopram administration enhanced affective memory performance because of a bias towards positive material but no significant changes in mood. Citalopram significantly increased plasma serotonin, adrenocorticotropic hormone and cortisol levels compared with placebo. Citalopram did not differentially affect the patient or control group. CONCLUSIONS: We have provided evidence that acutely increased serotonergic activity influences neuroendocrine responses and cognition in diarrhoea-predominant irritable bowel syndrome and controls without a significant effect on visceral perception.

Adolescent↗
PubMed2005

A case of metastasizing invasive hydatidiform mole. Is less--less good? Review of the literature with regard to adequate treatment.

BACKGROUND: Patients with invasive hydatidiform moles (IHM) have a good prognosis. Even if disease has spread, monocytostatic treatment might be sufficient if the diagnosis has been histologically confirmed. Established classifications divide gestational trophoblastic disease (GTD) including choriocarcinoma into cases with "high" and "low" risk. Without respect to histology "high-risk" cases are recommended to obtain polychemotherapy. CASE: A 40-year-old nullipara underwent hysterectomy for persistent vaginal bleeding after she had already been treated with curettage for hydatidiform mole. An IHM was pathohistologically confirmed. There were no signs of pulmonary spread or other metastases at the time of surgery. Postsurgically persistent beta-hCG levels lead to thorough staging, which revealed multiple pulmonary metastases and a vaginal metastasis. Despite metastasizing GTD with poor prognosis criteria she was treated with single agent therapy. Eight cycles of two weekly methotrexate (MTX) were administered. All sites of metastases responded and our patient is still fine after one year of follow-up. CONCLUSION: With respect to this and other reports monochemotherapy can be a reasonable primary treatment for metastatic IHM.

Adult↗
PubMed2004

Antigen-presenting cells in human endometrium during the menstrual cycle compared to early pregnancy.

OBJECTIVE: Human endometrium and early pregnancy decidua harbor a considerable and diverse population of antigen-presenting cells (APC). Changes in the number and distribution of macrophages and dendritic cells (DC) could point to a possible role of these immunocompetent cells in implantation and success of early pregnancy. METHODS: Uterine tissue was obtained from 22 women undergoing hysterectomy for bleeding disorders or dysmenorrhea and from 11 women undergoing legal abortion. Tissue was investigated with antibodies against CD14, CD68, CD83, DC-SIGN, Ki-67, and human leukocyte antigen (HLA)-DR using single and double immunohistochemical staining techniques. RESULTS: The number of CD14(+) cells was stable during all phases of the menstrual cycle and early pregnancy. In comparison to nonpregnant endometrium, DC-SIGN(+) cells showed a higher proliferation rate and were found associated in clusters with CD56(+) natural killer (NK) cells in early pregnancy. In the late secretory phase of the menstrual cycle, numbers of CD83(+) (P <.01) cells were significantly higher than in other endometrial phases and early pregnancy. HLA-DR(+) expression was significantly increased in early pregnancy but remained unchanged throughout the menstrual cycle. CONCLUSION: The presence of DC-SIGN(+) cells during the menstrual cycle and their proliferation in early pregnancy suggests an important role of these cells with regard to the balance between defense against pathogens and tolerance of the fetal allograft. Whether the increase of CD83(+) mature DC and CD68(+) macrophages in the late secretory phase is caused by hormonal stimuli and/or is due to changes of the cytokine/chemokine micromilieu remains to be investigated.

Abortion, Induced↗
PubMed2004

Laparoscopic enterolysis before adjuvant radiotherapy in a case of endometrial cancer.

CASE: A 33-year-old woman presenting with endometrial cancer stage FIGO Ic. After hysterectomy, bilateral oophorectomy and lymph node dissection, combined radiotherapy was indicated. Computer tomography scan was performed to plan radiotherapy and large bowel adhesions were found. To prevent bowel complications during radiation therapy, laparoscopic enterolysis of the adhesions was performed. We were able to start and apply radiation therapy only 22 days after initial laparotomy. Our patient had a history of deep vein thrombosis as a result of oral contraceptive medication. The endoscopic treatment enabled us to shorten the time of immobilization and bed rest substantially. CONCLUSION: Laparoscopy is an appropriate method to prevent complications due to radiotherapy.

Adult↗
PubMed2004

Lower high-density lipoprotein cholesterol and increased omega-6 polyunsaturated fatty acids in first-degree relatives of bipolar patients.

BACKGROUND: Lower serum high-density lipoprotein cholesterol and increased ratio of omega-6/omega-3 fatty acids have been reported in unipolar and bipolar depressed patients. Changes in cholesterol and fatty acids have been suggested to affect membrane viscosity and consequently serotonergic neurotransmitter expression. The goal of this study was to investigate whether lower baseline cholesterol and increased omega-6 and lower omega-3 fatty acids are present in healthy first-degree relatives of bipolar patients compared with controls and whether these changes were associated with neuroendocrine responses to an i.v. tryptophan challenge or mood. METHOD: Baseline cholesterol, fatty acids and mood were determined in healthy first-degree relatives of patients with bipolar disorders (N = 30) and healthy matched controls (N = 15) (parallel-group design). Prolactin and cortisol were measured following tryptophan infusion. RESULTS: First-degree relatives showed significantly lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids. Lower total omega-3 and higher total omega-6 fatty acids in phospholipids were positively correlated with peak prolactin response to tryptophan. Lower total omega-3 fatty acids in phospholipids and cholesteryl esters were associated with lower mood. CONCLUSIONS: Abnormalities of lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids in these subjects are in agreement with findings in bipolar and major depressed patients. Changes in fatty acids show an association with central serotonergic parameters. It is suggested that these abnormalities in cholesterol and fatty acids may constitute a trait marker for bipolar disorders.

Adult↗
PubMed2004

Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls.

BACKGROUND: Serotonin, a key denominator of the brain-gut axis, is involved in the regulation of gastrointestinal motility, secretion, and perception as well as cognition and mood. AIM: To assess the effects of an acutely lowered serotonin synthesis, using the acute tryptophan depletion (ATD) method, on visceral perception, affective memory performance, and mood in diarrhoea predominant irritable bowel syndrome patients (d-IBS) and controls. METHODS: In a randomised, double blind, crossover design, 14 d-IBS patients and fourteen matched controls were studied under ATD and placebo conditions, respectively. Perception of urge and pain was scored during rectal distensions. Affective memory performance, mood, and biochemical parameters of serotonergic metabolism were simultaneously assessed. RESULTS: ATD significantly decreased plasma tryptophan (67.0 (2.0) v 24.9 (2.0) mumol/l) and 5-hydroxyindole acetic acid concentrations (29.9 (1.0) v 15.8 (0.6) nmol/l). ATD was associated with significantly increased urge scores specifically in the lower pressure range and overall increased pain scores. ATD significantly lowered the perceptual threshold for first perception compared with placebo (patients 10.6 (1.2) v 13.6 (0.8) mm Hg, controls 12.6 (1.3) v 15.7 (1.2) mm Hg) but not for maximal tolerable discomfort (patients 50.5 (3.6) v 51.6 (3.3) mm Hg, controls 50.9 (3.3) v 48.8 (2.9) mm Hg). ATD induced a significant shift in affective memory bias towards preferential loss of positive material but no significant changes in mood. ATD did not differentially affect the patient or control group. CONCLUSIONS: We have provided evidence that serotonergic modulation by ATD affects both visceral perception as well as cognition in d-IBS and controls. Simultaneous measurement of brain and gut function and the application of ATD contribute to the elucidation of the complex pathophysiology of IBS.

Adult↗
PubMed2004

Different cardiorespiratory responses to hemorrhage and hyperoxia in normotensive (WKY) and spontaneously hypertensive (SHR) rats.

OBJECTIVE: To compare the cardiorespiratory responses underlying the beneficial effects of hyperoxia during blood loss between normotensive (WKY) and hypertensive (SHR) rats. METHODS: Experiments were carried out in anesthetized animals with both carotid bifurcations either innervated or denervated. The effects of breathing 60% O2 in N2 were studied either in combination with non-hypotensive hemorrhage or during hemorrhagic hypotension. RESULTS: In normoxia arterial pressure fell more in SHR than in WKY for a given blood loss. During hyperoxia, nerve-intact rats showed initial suppression of ventilation, but bifurcation-denervated rats a powerful enhancement. In all groups, hyperoxia increased the overall tone of venous capacitance vessels. CONCLUSIONS: The greater blood loss in SHR than in WKY when bleeding down to a given arterial pressure results from a stronger constriction of venous capacitance vessels. Hyperoxia improves the ability of the cardiorespiratory system to resist the effects of hemorrhage by increasing the overall venous tone, thus supporting cardiac filling, and in some cases also by increasing alveolar ventilation, probably secondary to improved cerebral oxygenation. The beneficial effects of hyperoxia were: (i) not prevented by carotid denervation, and thus were presumably direct tissue effects of oxygen, (ii) strikingly weaker in SHR than in normotensive (WKY) rats.

Animals↗
PubMed2003

Systematic review: serotonergic modulators in the treatment of irritable bowel syndrome--influence on psychiatric and gastrointestinal symptoms.

BACKGROUND: Both central and peripheral serotonergic modulators are used in the treatment of irritable bowel syndrome. The majority of patients with irritable bowel syndrome presenting to a gastroenterologist demonstrate affective dysregulation. Serotonin may play a regulatory role in both gastrointestinal motility and sensitivity, as well as in affective dysregulation, in irritable bowel syndrome. AIM: To analyse, systematically, randomized controlled trials studying the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome, in order to elucidate baseline irritable bowel syndrome symptomatology and possible differential effects of serotonergic modulation on this symptomatology. METHODS: A standardized qualitative analysis was performed of studies investigating the influence of serotonergic modulators on both gastrointestinal and psychiatric symptoms in irritable bowel syndrome using a blind review approach. The studies were ranked according to their total quality score (maximum 100 points). RESULTS: Eleven studies fulfilled the entry criteria, six of which scored above 55 points. An association between gastroenterological and psychiatric changes was present in five of the six studies. CONCLUSIONS: The results strengthen the serotonergic association between gastroenterological and psychiatric symptoms. Adjusted guidelines for combined gastrointestinal and psychiatric assessments are recommended in order to further elucidate the serotonergic interaction between gastrointestinal and psychiatric symptoms.

Colonic Diseases, Functional↗
PubMed2003

A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction.

BACKGROUND: The high incidence of post-stroke depression has been claimed to reflect a specific, stroke related pathogenesis in which lesion location plays an important role. To substantiate this claim, post-stroke depression should occur more often than depression after another acute, life threatening, disabling disease that does not involve cerebrovascular damage. OBJECTIVES: To compare the cumulative one year incidence of depression after stroke and after myocardial infarction, taking into consideration differences in age, sex, and the level of handicap. METHODS: In a longitudinal design, 190 first ever stroke patients and 200 first ever myocardial infarction patients were followed up for one year. Depression self rating scales were used as a screening instrument to detect patients with depressive symptoms. Major and minor depression was assessed at one, three, six, nine, and 12 months after stroke or myocardial infarction according to DSM-IV criteria, using the structured clinical interview from DSM-IV. The severity of depressive symptoms was measured with the Hamilton depression rating scale. Level of disability and handicap was rated with the Rankin handicap scale. RESULTS: The cumulative one year incidence of major and minor depression was 37.8% in stroke patients and 25% in patients with myocardial infarction (hazard ratio 1.6; p = 0.06). This difference disappeared after controlling for sex, age, and level of handicap. In addition, no differences were found in the severity of depressive symptoms or in the time of onset of the depressive episode after stroke or myocardial infarction. CONCLUSIONS: Depression occurs equally often during the first year after stroke and after myocardial infarction when non-specific factors such as sex, age, and level of handicap are taken into account. Thus the relatively high incidence of post-stroke depression seems not to reflect a specific pathogenic mechanism. Further research is needed to investigate whether vascular factors play a common role in the development of depression after stroke and myocardial infarction.

Aged↗
PubMed2002

Pronounced cognitive deficits following an intravenous L-tryptophan challenge in first-degree relatives of bipolar patients compared to healthy controls.

Cognitive impairment has repeatedly been described in bipolar disorders (BD). Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of BD patients. We investigated the effects of an intravenous (i.v.) tryptophan (Trp) challenge and placebo on cognitive performance in 30 healthy first-degree relatives of bipolar patients (FH) and 15 matched controls in a double-blind crossover design. A distinction was made between relatives of type I BD patients (FH I) and type II BD patients (FH II). Performances on planning, memory, attention, and psychomotor tasks were assessed 3 h after Trp infusion. After Trp, planning and attention were impaired in FH subjects but not in controls. Independent of Trp, FH subjects showed cognitive deficits on memory, focused and divided attention, and psychomotor performance. FH I subjects showed more pronounced cognitive impairments then FH II and controls. In all groups, Trp impaired memory and psychomotor performance significantly. In conclusions, cognitive deficits in FH following Trp may reflect a central 5-HT vulnerability in frontal brain areas. Independent of Trp, cognitive deficits in FH provide evidence for a trait marker for BD.

Adult↗
PubMed2002

Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood.

Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.

Adrenocorticotropic Hormone↗