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Biomedical subjects

J Huber

Publications and source records attributed to J Huber.

At least 37 records · Page 2Linked to original sources

Intra-specific and inter-specific recombination of tortricid-specific granuloviruses during co-infection in insect larvae.

Intra-specific recombination between two genotypes of the Cryptophlebia leucotreta granulovirus (CrleGV), namely CV3 and CV4, was studied by mixed infection experiments of larvae of C. leucotreta, followed by in vivo cloning and DNA restriction enzyme analyses of isolated progeny viruses. As a prerequisite for these studies a comparative restriction map for of CV3 and CV4 was constructed for eight restriction enzymes. The mixed infection experiments resulted in the isolation of the recombinant CrleGV CVR, which contained restriction sites typical for both parental viruses. Inter-specific recombination between two different granulovirus species, namely CrleGV CV3 and Cydia pomonella granulovirus (CpGV), was analogously investigated by mixed infections of larvae of C. leucotreta. A survey of more than 300 isolated CrleGV and CpGV clones did not reveal any recombinant, which indicated an extremely low recombination frequency in these experiments. By using a specific PCR approach, however, chimerical fragments from the highly conserved granulin gene sequence could be observed in DNA preparations of virus progeny. Cloning and sequencing indicated recombination between CrleGV and CpGV DNA. Our results suggest that recombination between granulovirus genotypes and granulovirus species result in eventually viable viruses and may contribute to the genetic diversity in this virus group.

Animals↗

Quality of blood pressure control and risk of cerebral bleeding in patients with oral anticoagulation.

BACKGROUND: We assessed how many patients on long-term oral anticoagulation (OAC) (i) suffer from arterial hypertension (AH), (ii) are aware of AH, (iii) need improvement of their therapy and (iv) suffer from cerebral bleeding. METHODS: Outpatients on long-term OAC were asked to measure blood pressure at least 4 times. Blood pressure was classified as normotensive if at least 75 % of all measurements were < 139/89 mm Hg; as mild/moderate AH if > 25 % of all measurements were 140 - 179 mm Hg systolic or 90 - 109 mm Hg diastolic; and as severe AH if > 25 % of all measurements were > 180 mm Hg systolic or > 110 mm Hg diastolic. Bleeding complications were registered. RESULTS: Of the 235 patients (108 female, 67 +/- 12 years), 80 % suffered from AH. Severe AH was present in 5 %. Only 56 % were aware of suffering from AH. An improvement of antihypertensive therapy was needed in 64 %. Over 225 days, only one cerebral bleeding occurred. Blood pressure was normotensive in 30 % with known AH. CONCLUSIONS: Blood pressure control seems better in OAC patients than in normals, if the patient is aware of AH. Patients with AH on OAC are not aware of AH in > 50 %. Repeated blood pressure measurements in OAC are recommended, even if patients are not aware of AH.

Administration, Oral↗

Fuhrmann syndrome: two Brazilian cases.

We describe two unrelated boys with bilateral fibula aplasia, poly- and oligodactyly, and bowed tibiae in two non-consanguineous Brazilian families. These cases are similar to those reported by Fuhrman et al. [(1980). Skeletal Dysplasias. New York: Alan R. Liss Inc. pp. 519-524].

Fibula↗

Clinical evaluation of the WOMAC 3.0 OA Index in numeric rating scale format using a computerized touch screen version.

BACKGROUND: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index is a previously described self-administered questionnaire covering three domains: pain, stiffness and function. It has been validated in patients with osteoarthritis (OA) of the hip or knee in a paper-based format. AIM: To validate the WOMAC 3.0 using a numerical rating scale in a computerized touch screen format allowing immediate evaluation of the questionnaire. In the computed version cartoons, written and audio instruments were included in order facilitate application. METHODS: Fifty patients, demographically balanced, with radiographically proven primary hip or knee OA completed the classical paper and the new computerized WOMAC version. Subjects were randomized either to paper format or computerized format first to balance possible order effects. RESULTS: The intra-class correlation coefficients for pain, stiffness and function values were 0.915, 0.745 and 0.940, respectively. The Spearman correlation coefficients for pain, stiffness and function were 0.88, 0.77 and 0.87, respectively. CONCLUSION: These data indicate that the computerized WOMAC OA index 3.0 is comparable to the paper WOMAC in all three dimensions. The computerized version would allow physicians to get an immediate result and if present a direct comparison with a previous exam.

Adult↗

Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women.

OBJECTIVE: To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability. DESIGN: A double-blind, randomised comparative trial. SETTING: Thirty-seven centres in six European countries. POPULATION: Five hundred and one postmenopausal women, under 65 years of age with an intact uterus. INTERVENTIONS: For 12 months, women received daily treatment with tibolone 2.5 mg (n = 250), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE-MPA, n = 251). MAIN OUTCOME MEASURES: The primary outcome was vaginal bleeding rate during cycles 4-6. The secondary outcomes were vaginal bleeding rate during cycles 1-3, 7-9 and 10-13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability. RESULTS: Treatment with tibolone led to a significantly lower bleeding rate during cycles 4-6 compared with CEE-MPA (15.0% vs 26.9%; P = 0.004); there was a similar difference during cycles 1-3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE-MPA at 12 months (P = 0.017). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE-MPA (2.4% vs 17.1%; P < 0.001). CONCLUSION: The vaginal bleeding rate during cycles 4-6 was significantly lower in women using tibolone. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone.

Drug Combinations↗

The surgical treatment of bony metastases of the spine and limbs.

The skeleton is the most common site to be affected by metastatic cancer. The place of surgical treatment and of different techniques of reconstruction has not been clearly defined. We have studied the rate of survival of 94 patients and the results of the surgical treatment of 91 metastases of the limbs and pelvis, and 18 of the spine. Variables included the different primary tumours, the metastatic load at the time of operation, the surgical margin, and the different techniques of reconstruction. The survival rate was 0.54 at one year and 0.27 at three years. Absence of visceral metastases and of a pathological fracture, a time interval of more than three years between the diagnosis of cancer and that of the first skeletal metastasis, thyroid carcinoma, prostate carcinoma, renal-cell carcinoma, breast cancer, and plasmacytoma were positive variables with regard to survival. The metastatic load of the skeleton and the surgical margin were not of significant influence. In tumours of the limbs and pelvis, the local failure rate was 0% after biological reconstruction (10), 3.6% after cemented or uncemented osteosynthesis (28) and 1.8% after prosthetic replacement (53). The local failure rate after stabilisation of the spine (18) was 16.6%. There was local recurrence in seven patients (6.4%), and in four of these the primary tumour was a renal-cell carcinoma. The local recurrence rate was 0% after extralesional (24) and 8.2% after intralesional resection (85). Improvements in the oncological management of patients with primary and metastatic disease have resulted in an increased survival rate. In order to avoid additional surgery, it is essential to consider the expected time of survival of the reconstruction and, in bony metastases with a potentially poor response to radiotherapy, the surgical margin.

Adolescent↗

Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition.

Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5 (n-3)) inhibit T lymphocyte activation probably by displacing acylated signaling proteins from membrane lipid rafts. Under physiological conditions, saturated fatty acyl residues of such proteins partition into the cytoplasmic membrane lipid leaflet with high affinity for rafts that are enriched in saturated fatty acyl-containing lipids. However, the biochemical alteration causing displacement of acylated proteins from rafts in PUFA-treated T cells is still under debate but could principally be attributed to altered protein acylation or changes in raft lipid composition. We show that treatment of Jurkat T cells with polyunsaturated eicosapentaenoic acid (20:5 (n-3)) results in marked enrichment of PUFAs (20:5; 22:5) in lipids from isolated rafts. Moreover, PUFAs were significantly incorporated into phosphatidylethanolamine that predominantly resides in the cytoplasmic membrane lipid leaflet. Notably, palmitate-labeled Src family kinase Lck and the linker for activation of T cells (LAT) were both displaced from lipid rafts indicating that acylation by PUFAs is not required for protein displacement from rafts in PUFA-treated T cells. In conclusion, these data provide strong evidence that displacement of acylated proteins from rafts in PUFA-treated T cells is predominantly due to altered raft lipid composition.

Acylation↗

Ovarian function during and after treatment with the new progestagen Org 30659.

OBJECTIVE: To evaluate ovarian function during 21 days of oral administration of different doses of Org 30659, a novel selective progestagenic steroid. DESIGN: Randomized, double-blind, dose-finding study. SETTINGS: Three centers in Austria, Sweden, and the United Kingdom. PARTICIPANTS: Eighty-one healthy women 19-40 years of age with regular ovulatory cycles. INTERVENTION: Daily oral administration of 0.060, 0.120, 0.180, or 0.240 mg of Org 30659, or 0.075 mg desogestrel (reference group), for 21 days. MAIN OUTCOME MEASURE(S): Once-daily measurements of follicular diameter and 17-beta estradiol, progesterone, FSH, and LH levels. RESULT(S): Daily treatment with Org 30659 for 21 days caused dose-dependent suppression of ovarian activity. No ovulation was observed in any study group. On average, ovulation returned 16.5 to 22.1 days after treatment. The effects of desogestrel, 0.075 mg, were similar to those of 0.060 and 0.120 mg of Org 30659. All doses were well tolerated, as shown by the type of side effects that occurred, the absence of an effect on physical and laboratory findings, and the low rate of study discontinuation. CONCLUSION(S): Daily oral administration of 0.060-0.240 mg of Org 30659 suppresses ovarian function to a level sufficient to inhibit ovulation. This effect is dose-dependent, and the suppressive effect is readily reversible at all doses tested. Org 30659 can thus be safely administered orally for 21 days to healthy female volunteers in a dosage of 0.060 mg/d to 0.240 mg/d.

Adult↗

Altered responsiveness to stress and NMDA following prenatal exposure to cocaine.

Pregnant Sprague--Dawley rats were treated once daily with 40-mg/kg cocaine or saline from gestation days (GD) 12 to 21. A third group of pregnant dams was used as a pairfed control. Male and female offspring were examined for stress endurance response as determined by the cold-water swim test on postnatal days (PND) 21, 30, 40, and 60. Male and female offspring exposed to cocaine in utero were found to have diminished tolerance and altered hormonal response to stress. Moreover, prenatal cocaine exposure has been associated with significant increases in severity of N-methyl-D-aspartate (NMDA; 35 mg/kg) behavioral responses (tail twitches, wetdog shaking, and convulsion) as compared to control. Examining the experimental groups for pain sensitivity using the tail-flick and the hot-plate methods indicated that prenatal cocaine exposure altered pain sensitivity. NMDA receptor binding studies showed an increase in receptor density in the hippocampus and hypothalamus of the cocaine-treated group. These results indicate that gestational cocaine exposure is associated with long-term alterations in response to stress, NMDA receptor, and pain sensitivity in the rat offspring.

Aging↗

Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells.

The neuropathology associated with Parkinson's disease within and around the substantia nigra is thought to involve excessive production of free radicals, dopamine autoxidation, defects in the expression of glutathione peroxidase, attenuated levels of reduced glutathione, altered calcium homeostasis, excitotoxicity and genetic defects in mitochondrial complex I activity. While the neurotoxic mechanisms are vastly different for excitotoxins and N-methyl-4-phenylpyridinium ion (MPP+), both are thought to involve free radical production, compromised mitochondrial activity and excessive lipid peroxidation. In the present study, several dietary antioxidant compounds, monoamine oxidase inhibitors and ergogenic compounds were examined for protective action against neurotoxicity induced by L-glutamate (15 mM) or MPP+-HCl (5 mM) in a plastic adhering variant of murine pheochromocytoma cells. The results show no significant protective effects exhibited by azulene, (+)-catechin, curcrumin, (-)-epigallocatechin gallate, green tea, morin, pygnogenol, silymarin, clove oil, garlic oil or rosemary, extract. Compounds, which were effective in providing protection against L-glutamate-induced cell death, were coenzyme Q-0, coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. Compounds, which provided protection against MPP+-HCl toxicity, were allopurinol, coenzyme Q-10, L-deprenyl, N-acetyl-L-cysteine and sesame oil. In both models, significant protection was achieved in the presence of coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. These results indicate that the mechanism of cell death in both of these toxicity models is most likely not related to the destructive effects of free radicals.

1-Methyl-4-phenylpyridinium↗

The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model.

The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation.

Animals↗

Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients.

The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche, thymopsyche, personality and psychophysiological measures of menopausal syndrome patients was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2 mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg + dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in the analysis of the double-blind phase. Both the double-blind and the open-label phase lasted 2 months. Noopsychic investigations demonstrated an improvement in associative verbal memory after 2 months of regimen A, which was significant as compared with both baseline and placebo. Regarding visual memory, regimen A* induced an improvement, which was significantly different from the decline in correct reproductions in the Benton Test observed under estradiol. Errors in the Benton Test decreased significantly after regimen A* as compared with regimen EV. These findings suggest that hormone replacement therapy with estradiol, and even more in combination with dienogest, improves verbal and visual memory, which is in line with the improvement in information processing speed and capacity objectified by event-related potentials (ERP). Thymopsychic investigations demonstrated a significant improvement in somatic complaints and trait anxiety after both regimen A and regimen EV as compared with baseline. State anxiety decreased significantly under regimen A* as compared with EV. The Freiburger Personality Inventory showed an improvement in aggressivity after regimen A* as compared with the preceding placebo as well as an improvement in striving after dominancy after both regimen A and regimen EV as compared with pre-treatment, but also after regimen A* as compared with regimen EV. Extraversion increased after 2 months of regimen A as compared to regimen P. Psychophysiological findings including pupillary and skin conductance variables were not significant.

Affect↗

Immunological and dermatological impact of progesterone.

C21 steroids and especially progesterone are involved in various physiological processes besides reproduction. Langerhans cells are becoming a major topic in immunology and, from this point, it is of high interest that progesterone is able to increase the number of Langerhans cells in different epithelial cells. This has an impact for a gender specificity of HIV1 infection, and also for the high premenstrual incidence of sexually transmitted diseases. Matrix metalloproteinase activity is of high physiological importance for tissue regeneration; progesterone suppresses the expression of some members of the matrix metalloproteinase super-family and reduces the collagenolytic activity. These effects can be observed during pregnancy, but are not only apparent on the myometrium; the suppressing effect of progesterone on matrix metalloproteinases can also be observed in the skin. The dermatological aspect of this observation is discussed.

Acquired Immunodeficiency Syndrome↗

Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome.

Body composition, fat distribution and bone mineral density were examined in lean women suffering from polycystic ovary syndrome (PCOS) and compared with body composition and fat distribution characteristics of weight-matched lean controls. Ten women with PCOS and a body mass index (BMI) below 25.00 (kg/m(2)) and 10 healthy women with a BMI below 25.00 (kg/m(2)) matched for age and weight and BMI as controls were enrolled in this study. Body composition and bone density were measured by dual-energy- x-ray-absorptiometry and fat distribution patterns were calculated. Although matched for age, weight and BMI, lean PCOS patients showed a significantly higher amount of body fat and lower amount of lean body mass than the controls. The majority of PCOS patients showed an intermediate or android kind of fat distribution. Only 30% of the lean PCOS patients corresponded to the definition of gynoid fat distribution while this was true of all lean controls.

Absorptiometry, Photon↗

Quality control of mitigation methods for unusually high indoor radon concentrations.

The present study's objective was to control the quality of different mitigation methods for unusually high indoor radon (222Rn) concentrations of up to 274,000 Bq m(-3) in a village (Umhausen, 2,600 inhabitants) in western Tyrol, Austria. Five years after mitigation, five different remedial actions were examined on their quality by means of measuring indoor radon concentrations with charcoal liquid scintillation radon detectors and with a continuously recording AlphaGuard detector. Mitigation method in house 1--a mechanical intake and outlet ventilation system with heat exchanger in the basement, combined with a soil depressurization system--was characterized by long-term stability. With most favorable air pressure (+100 Pa) in the basement, mean basement radon concentrations in the winter were reduced from 200,000 Bq m(-3) to 3,000 Bq m(-3) by this method 5 y after mitigation. Acting against experts' instructions, the inhabitants had switched off the ventilation system most of the time to minimize power consumption although it had been proven that ventilation reduced mean basement radon concentration by a factor of about 3 in the winter and about 15 in the summer. Mitigation method in house 2-soil depressurization with two fans and loops of drainage tubes to withdraw radon from the region below the floor and outside the basement walls, and from soil below that part of the house with no basement-had been the most successful remedial measure until the winter of 1999 (i.e., 6 y after mitigation), when micro-cracks opened and consequently mean basement radon concentration increased from 250 Bq m(-3) to 1,500 Bq m(-3). Measures to block these microcracks and to minimize soil drying are being developed. Five years after mitigation, the remedial method used in house 3--a multilayer floor construction, where a fan was used to suck radon from a layer between bottom slab and floor-reduced winter mean radon concentration from 25,000 Bq m(-3) to 1,200 Bq m(-3), with the ventilation on and the basement door open. Mitigation method in house 4--a basement sealing technique--was unsuccessful with almost identical radon concentrations during all the five years since mitigation had started. Mitigation method in house 5--a waterproof basement technique especially for future homes--reduced mean basement radon concentration below 300 Bq m(-3) and mean ground floor radon concentration below 200 Bq m(-3), which is the Austrian action level for newly constructed buildings. These findings indicate that even in areas with extremely high radon concentrations, effective mitigation of indoor radon can be achieved provided that house-specific long-term, stable mitigation techniques are applied.

Air Pollution, Indoor↗

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats.

Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), fluoxetine (20 mg/kg) sertraline (30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine and moclobemide increased blood glucose at different times after the glucose overload. Sertraline neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, sertraline neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether sertraline is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

Acute Disease↗