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Biomedical subjects

D Gruber

Publications and source records attributed to D Gruber.

At least 19 recordsLinked to original sources
PubMed2003

Collagen expression in tissue engineered cartilage of aged human articular chondrocytes in a rotating bioreactor.

This study describes the culture and three-dimensional assembly of aged human articular chondrocytes under controlled oxygenation and low shear stress in a rotating-wall vessel. Chondrocytes cultured in monolayer were released and placed without any scaffold as a single cell suspension in a rotating bioreactor for 12 weeks. Samples were analyzed with immunohistochemistry, molecular biology and electron microscopy. During serial monolayer cultures chondrocytes dedifferentiated to a "fibroblast-like" structure and produced predominantly collagen type I. When these dedifferentiated cells were transferred to the rotating bioreactor, the cells showed a spontaneous aggregation and formation of solid tissue during the culture time. Expression of collagen type II and other components critical for the extracellular cartilage matrix could be detected. Transmission electron microscopy revealed a fine network of randomly distributed collagen fibrils. This rotating bioreactor proves to be a useful tool for providing an environment that enables dedifferentiated chondrocytes to redifferentiate and produce a cartilage-specific extracellular matrix.

Age Factors↗
PubMed2001

Abundant expression of the microtubule-associated protein, ensconsin (E-MAP-115), alters the cellular response to Taxol.

Correlation between expression level of a microtubule-associated protein called ensconsin (E-MAP-115) and degree of Taxol sensitivity in several cultured cell lines prompted us to investigate potential cause-and-effect relationships between ensconsin level and Taxol action. We used human MCF-7 or HeLa cells, which are sensitive to low Taxol concentrations (LD(50) of 30-35 and 3.5 nM, respectively) to prepare stably transfected populations of cells expressing heterogeneous levels of ensconsin chimeras, either green fluorescent protein (GFP) conjugated to full-length ensconsin (GFP-Ensc) or to ensconsin's microtubule-binding domain (GFP-EMTB). Both a subjective microscopic assay, i.e., scoring fluorescence of GFP-ensconsin chimeras following Taxol treatment, and a quantitative immunobiochemical assay, i.e., measuring level of GFP-ensconsin chimera in cells surviving treatment with Taxol, showed that cells expressing higher levels of GFP-ensconsin chimera were killed more readily by Taxol concentrations approaching the LD(50). In contrast, in TC-7 cells, which are relatively insensitive to Taxol (LD(50) > 600 nM), high-level expression of GFP-EMTB conferred no significant susceptibility to killing by Taxol. However, heightening the Taxol sensitivity of GFP-EMTB-TC-7 cells by pre-incubating cells with the p-glycoprotein inhibitor, verapamil, did result in selective killing of cells highly expressing GFP-EMTB. Taken together, results obtained in MCF-7, HeLa, and TC-7 cells suggest that elevated ensconsin level bestowed a selective disadvantage upon Taxol-sensitive cells. To probe potential mechanisms by which ensconsin could alter the Taxol response, we isolated microtubules from HeLa cells that were or were not pretreated with Taxol. In vivo Taxol treatment significantly tightened microtubule-binding of ensconsin, suggesting that Taxol alters ensconsin's microtubule-binding properties and may, in turn, alter the Taxol response of the microtubules. Our data support the hypothesis that Taxol works synergistically or in concert with microtubule-binding proteins in bringing about deleterious effects on the microtubule cytoskeleton.

Animals↗
PubMed2001

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↗
PubMed2001

Phosphorylation of MAP4 affects microtubule properties and cell cycle progression.

In human cells, MAP4, a microtubule-associated protein ubiquitously expressed in proliferating cells, has been shown to undergo in vivo phosphorylation. Two phosphorylation sites, serines 696 and 787, lie within the proline-rich region of its microtubule-binding domain. To test the hypothesis that phosphorylation at these sites influences microtubule properties or cell cycle progression, we prepared stable cell lines that inducibly express versions of MAP4 in which phosphorylation of these two serines was prevented by their replacement with alanine, lysine, or glutamate residues (AA-, KK-, or EE-MAP4). All nonphosphorylatable mutant forms of MAP4 expressed in mouse Ltk- cells were localized to MT arrays that were unremarkable in appearance. Expression of nonphosphorylatable mutants of MAP4 did not affect cell doubling time; however, expression of some mutants altered progression into or through cell division. Interactions of mutant MAP4 with MTs were examined in vitro. KK mutant MAP4 bound MTs more avidly than its wild-type counterpart, WT-MAP4. In vivo MT polymer also differed among the mutants: MTs in cells expressing the KK- and AA-MAP4 forms were more resistant to nocodazole depolymerization than those in cells expressing EE- or WT-MAP4 forms. Our results demonstrate that phosphorylation alters MAP4 properties and suggest a raison d'être for phosphorylation of the MAP4 microtubule-binding domain during cell cycle progression.

Amino Acid Sequence↗
PubMed2000

[Hormone replacement therapy with a transdermal estradiol gel and oral micronized progesterone. Effect on menopausal symptoms and lipid metabolism].

In a multicenter observational study, the efficacy and acceptance of two different regimens of postmenopausal hormone replacement therapy in the form of a combination of 17 beta-estradiol in percutaneous gel application and micronized oral progesterone were evaluated. Forty-eight patients (aged 40-66 years) received 2.5 g estradiol gel plus either continuously micronized progesterone 100 per day (group A) or, sequentially, 200 mg per day between day 16 and 25 of a monthly cycle (group B) for two months. A significant reduction in typical menopausal symptoms, especially vasomotor complaints like hot flushes or sweating, was observed in both groups (score average at the beginning for hot flushes: 2.0 in group A and 1.8 in group B; after two months of treatment, 0.7 in group A and 0.4 in group B). Cholesterol levels were slightly reduced but statistically significant (235.9 +/- 49.55 mg/dl vs. 226.3 +/- 52.24 mg/dl; p < 0.05) only in group A; a trend towards lower cholesterol was observed in group B (236.5 +/- 47.82 mg/dl vs. 227.4 +/- 44.72 mg/dl). Lipoprotein (a) was also significantly reduced in group A (32.57 +/- 36.52 mg/dl vs. 28.28 +/- 31.03 mg/dl in group A; 31.7 +/- 28.42 mg/dl vs. 28.34 +/- 23.71 in group B; p < 0.05). The overall acceptance of this therapy was excellent or good in 91.3% of group A and 92.8% of group B patients.

Administration, Cutaneous↗
PubMed2000

Clinical profile of a new hormone replacement therapy containing 2 mg 17 beta-estradiol and 10 mg dydrogesterone.

OBJECTIVE: Patient's acceptability, compliance, and effectiveness of a new sequential hormone replacement regimen containing 2 mg 17beta-estradiol and 10 mg dydrogesterone, were assessed in a 3-month, open, multicentre study involving 110 menopausal women. METHODS: A specially designed menopause score was used to assess the severity of menopausal symptoms, each symptom being graded at baseline and after 3 months on a four-point scale. Bleeding data were recorded by the patient on a diary card. Serum hormone levels including FSH, LH, E2, P, PRL, DHEA-S, T, SHBG were checked at the initial visit and at the end of the study. RESULTS: After 3 months of treatment, all but four of the 34 climacteric symptoms investigated showed a significant improvement. There were no significant changes noted in body weight. The average duration and flow of bleeding showed no significant changes during hormone replacement therapy (HRT). There were no serious adverse events related to treatment. CONCLUSION: The 17beta-estradiol/dydrogesterone combination HRT reduced effectively climacteric symptoms, showed no significant changes in endometrial thickness as determined by transvaginal ultrasonography and provided excellent cycle control.

Adult↗
PubMed2000

Hysterectomy is associated with postmenopausal body composition characteristics.

The impact of hysterectomy without oophorectomy and with no malignant purpose on body composition and postmenopausal weight gain was tested in 184 Viennese females aged between 47 and 57 years (mean 52.9). Hysterectomized women were significantly heavier than those who experienced a spontaneous menopause (controls). The amount of fat tissue, especially in the abdominal region, was significantly higher in hysterectomized women. Furthermore, they were reported to have experienced a significantly higher weight gain since menopause (9.1 versus 6.0 kg). No significant differences in bone mass were found. Psychological stress factors and hormonal changes following hysterectomy are discussed as possible causes of these differences.

Absorptiometry, Photon↗
PubMed2000

The doctrine of two schools of thought--a shield or a sword.

This paper recognizes that, in medicine at least, there are at least two ways of looking at a problem, be it clinical or legal. The subject is approached from both viewpoints. Emphasis is placed on the background of legal concepts and their application to clinical situations. To illustrate the doctrine, the authors have drawn extensively on case law arising mainly in Israel, but also in the USA and Europe.

Decision Making↗
PubMed1999

Postmenopausal weight status, body composition and body fat distribution in relation to parameters of menstrual and reproductive history.

OBJECTIVES: In the present study the association between menstrual and reproductive history patterns and weight status, fat distribution and body composition during postmenopause was tested. METHODS: In 106 healthy postmenopausal women ranging in age from 48 to 58 years (x = 53.7 year) the weight status was classified according to the recommendations of the WHO. Additionally body composition was estimated by dual energy X-ray absorptiometry and fat distribution was calculated using the fat distribution index. Weight status, body composition and fat distribution were correlated with self-reported parameters of menstrual and reproductive history (age at menarche, average cycle length, number of births, age at first and last birth, average pregnancy weight gain, age at menopause). RESULTS: It was shown that number of births, age at first birth and pregnancy weight gain were related significantly to the postmenopausal weight status, body composition and fat distribution. CONCLUSION: An early first birth a low number of births and a high weight gain during pregnancies can be assumed as risk factors for overweight, a higher amount of adipose tissue, android fat patterning and therefore for the development of the metabolic syndrome during postmenopause. In contrast no adverse effect of menstrual and reproductive parameters on postmenopausal bone mass was found.

Adipose Tissue↗
PubMed1999

The influence of female sex hormones on nasal reactivity in seasonal allergic rhinitis.

BACKGROUND: This study aimed to investigate whether the hormone peaks of estrogen and progesterone could influence the extent of the allergic reaction in grass-pollen-allergic women. METHODS: Twenty-three allergic women with seasonal allergic rhinitis due to grass pollen were included in this trial. Twelve were taking oral contraceptives (OC) (control group), and 11 were taking no pill (target group). The subjects were challenged with grass pollen by nasal provocation test around day 14 of their menstrual cycle (ovulation day) and again at the end of the cycle (day 27). The primary criteria were the subjective nasal symptoms rhinorrhea, nasal blockage, itching, and sneezing. A further criterion was the objectively measured nasal mucosal swelling, assessed by active anterior rhinomanometry. All criteria were evaluated before and 15 min after provocation, and the hormone status was determined on each investigation day. RESULTS: Comparisons of symptoms between the groups resulted in P values of > 0.05 for all symptoms at both visits except the symptom blocked nose, which was significantly lower (P=0.03) in the patients with OC intake at visit 2, and the symptom sneezing, which showed a significantly (P=0.02) higher increase in patients taking OC at the end of the cycle. The flow decrease reached a greater extent in the target group than in the controls. CONCLUSIONS: These results indicate a correlation of the hormonal situation and the nasal allergic reactivity. OC intake led to an intensifying of neurogenic symptoms near the end of pill intake, a result which could be due to a protective effect of the endogenous progesterone, in contrast to the orally administered hormones.

Adult↗
PubMed1999

Sulfonylureas and ischaemic preconditioning; a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide.

AIMS: Glimepiride is a new sulfonylurea for diabetes treatment which is supposed to impact less on extra-pancreatic ATP-dependent K+ channels than the conventional drug glibenclamide. This study was performed to evaluate whether this results in a better maintenance of ATP-dependent K+ channel mediated ischaemic myocardial preconditioning. METHODS AND RESULTS: In a double-blind placebo-controlled study the period of total coronary occlusion during balloon angioplasty of high grade coronary artery stenoses was used as a model to compare the effects of both drugs. Quantification of myocardial ischaemia was achieved by recording the intracoronary ECG and the time to the occurrence of angina during vessel occlusion. All patients underwent three dilatations. The first dilatation (dilatation 1) served to determine the severity of ischaemia during vessel occlusion. During dilatation 2, baseline values were recorded. Thereafter, glimepiride (15 patients: 1.162 mg), glibenclamide (15 patients: 2.54 mg) or placebo (15 patients) were intravenously administered over 12 min. Dilatation 3 started 10 min after the beginning of the drug administration. Mean ST segment shifts in the placebo group decreased by 35% (dilatation 2: 0.23; dilatation 3:0.15 mV; CI -0.55 to 0.00 mV; P=0.049). A similar reduction also occurred in the glimepiride group, in which repetitive balloon occlusion led to a 34% reduction (dilatation 2: 0.35; dilatation 3: 0.23 mV; CI -0.21 to -0.02 mV; P=0.01). There was little influence however, on mean ST segment shifts in the glibenclamide group (dilatation 2 and dilatation 3: 0.24 mV; CI -0.10 to 0.25 mV; P=0.34). Accordingly, time to angina during balloon occlusion slightly increased (by 30%) in the placebo group (dilatation 2: 37 s; dilatation 3: 48 s; CI 0.0 to 15.0 s; P=0.16); increased by 13% in the glimepiride group (dilatation 2: 40 s; dilatation 3: 45 s; CI 0.0 to 14.0 s; P=0023); and remained unchanged in the glibenclamide group (dilatation 2 and dilatation 3: 30 s; CI -7.5 to 7.5 s; P=0.67). CONCLUSION: These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it.

Adult↗
PubMed1999

The role of oxytocin in relation to female sexual arousal.

Oxytocin is clearly involved in human reproduction and serves an important role in sexual arousal. Oxytocin serum levels were measured before and after sexual stimulation in 12 healthy women. Values of oxytocin 1 min after orgasm were significantly higher (p < 0.05) than baseline levels. This finding supports the hypothesis that oxytocin plays a major part in human sexual response both in neuroendocrine function and postcoital behavior.

Adult↗
PubMed1999

Microtubule-associated protein 4 (MAP4) regulates assembly, protomer-polymer partitioning and synthesis of tubulin in cultured cells.

We depleted MAP4, a ubiquitously expressed microtubule (MT)-associated protein previously shown to be capable of stabilizing MTs, from HeLa cells by stably expressing antisense RNA. These HeLa-AS cells, in which the MAP4 level was decreased to 33% of the wild-type level, displayed decreased content of total tubulin (65% of the wild-type level). The partitioning of cellular tubulin into protomer and polymer was altered in HeLa-AS cells: polymeric tubulin was decreased to 46% of the level in control cells, while protomeric tubulin was increased to 226% of the level in control cells. Tubulin protein synthesis was decreased, consistent with the tubulin autoregulation model, which proposes that tubulin protomer inhibits its own synthesis. Following release from drug-induced depolymerization, MTs in HeLa-AS cells reformed more slowly, and showed an increased focus on the centrosome, as compared to control cells. HeLa-AS cells also appeared to be less bipolar in shape and flatter than control cells. Our data suggest that MAP4 regulates assembly level of MTs and, perhaps through this mechanism, is involved in controlling spreading and shape of cells.

Biopolymers↗
PubMed1999

E-MAP-115 (ensconsin) associates dynamically with microtubules in vivo and is not a physiological modulator of microtubule dynamics.

Microtubule-associated proteins (MAPs) have been hypothesized to regulate microtubule dynamics and/or functions. To test hypotheses concerning E-MAP-115 (ensconsin) function, we prepared stable cell lines expressing conjugates in which the full-length MAP (Ensc) or its microtubule-binding domain (EMTB) was conjugated to one or more green fluorescent protein (GFP) molecules. Because both distribution and microtubule-binding properties of GFP-Ensc, GFP-EMTB, and 2x, 3x, or 4xGFP-EMTB chimeras all appeared to be identical to those of endogenous E-MAP-115 (ensconsin), we used the 2xGFP-EMTB molecule as a reporter for the behavior and microtubule-binding function of endogenous MAP. Dual wavelength time-lapse fluorescence imaging of 2xGFP-EMTB in cells microinjected with labeled tubulin revealed that this GFP-MAP chimera associated with the lattice of all microtubules immediately upon polymerization and dissociated concomitant with depolymerization, suggesting that dynamics of MAP:microtubule interactions were at least as rapid as tubulin:microtubule dynamics in the polymerization reaction. Presence of both GFP-EMTB chimeras and endogenous E-MAP-115 (ensconsin) along apparently all cellular microtubules at all cell cycle stages suggested that the MAP might function in modulating stability or dynamics of microtubules, a capability shown previously in transiently transfected cells. Although cells with extremely high expression levels of GFP-EMTB chimera exhibited stabilized microtubules, cells expressing four to ten times the physiological level of endogenous MAP exhibited microtubule dynamics indistinguishable from those of untransfected cells. This result shows that E-MAP-115 (ensconsin) is unlikely to function as a microtubule stabilizer in vivo. Instead, this MAP most likely serves to modulate microtubule functions or interactions with other cytoskeletal elements.

Female↗
PubMed1999

[Non-penetrating deep sclerectomy in the surgical treatment of chronic open-angle glaucoma. Mid-term results].

PURPOSE: Non-penetrating deep sclerectomy has been performed in France since the early nineties and appears to be an interesting alternative to Cairn's trabeculectomy. The technical characteristics, the ability to use antimitotic procedures and postoperative YAG laser goniotomy contribute to make deep sclerectomy an attractive surgical method. We evaluated its efficacy and adverse effects in a mid-term retrospective series. PATIENTS AND METHODS: Fifty patients (all POAG) without usually accepted failure risks for trabeculectomy (trabeculoretraction less than 3 months, intraocular anterior or posterior lens, aphakia, black or Asian subject, failure of previous surgical procedure, patients under 40) underwent this surgical procedure between June 96 and October 97 performed by several skilled surgeons in our unit. This was the first antiglaucoma surgical procedure for all patients. Collagen draining implant was not used. Two pressure criteria (21 mmHg and 16 mmHg) were used to assess success. Success rate and adverse effects were compared with previously published data using the Kaplan-Meier test. RESULTS: Medium follow-up was 14.24 months. The success rate was 81% (IOP 21 mmHg) and 50% (IOP 16 mmHg) at maximum follow-up of 18 months. There was no statistical difference between treated and untreated groups for target IOP at 21 mmHg (p = 0.12). These results were comparable to those in previous studies and to those obtained with trabeculectomy. The complication rate was low (hyphema 0%, choroidal detachment 2%, hypothalamia 2%, endocular infection 0%). DISCUSSION: Our success rate and complication rate were comparable with previously published series. Choosing a target IOP of 16 mmHg allowed a better comparison between daily clinical observations and mid-term results, showing a significant difference from the 21 mmHg target. Nevertheless, the success rate was comparable to that obtained with trabeculectomy and the complication rate was lower, supporting the favorable opinion concerning deep sclerectomy. CONCLUSION: Non-penetrating deep sclerectomy appears to be as efficient as Cairn's trabeculectomy for surgical treatment of glaucoma and allows a lower complication rate. Long-term results, visual field and papilla remain to be evaluated. Furthermore, results with a pressure goal of 16 mmHg are interesting to evaluate because they reflect the real clinical situation better than the target 21 mmHg IOP. This technique should be evaluated in other forms of glaucoma.

Actuarial Analysis↗
PubMed1998

Reduction of intraocular pressure in a glaucoma patient undergoing hormone replacement therapy.

OBJECTIVES: To show the reducing effect of estrogens and progestins on the elevated intraocular pressure (IOP) in the case of a 56-year-old woman showing typical climacteric complaints, who was admitted to the menopause outpatient unit. She also suffered from a primary open-angle glaucoma treated with betaophtiole eye drops with intraocular pressures of 16-20 mmHg under this local therapy. METHODS: IOP patterns were monitored by means of standardised daily pressure profiles four times a day before as well as 4 and 12 weeks after the beginning of hormone replacement therapy (HRT). The local glaucoma therapy remained unchanged. RESULTS: During HRT, IOP levels were reduced from 16-20 mmHg before therapy to 12-15 mmHg at week 4 and to 13-15 mmHg at week 12 after the beginning of HRT. CONCLUSION: The finding of a close chronological relationship between the onset of menopause and the development of a glaucoma is a potentially new indication for HRT.

Antihypertensive Agents↗
PubMed1998

Impact of the age at menarche on adult body composition in healthy pre- and postmenopausal women.

The present study focuses on the impact of age at menarche on body composition development during adulthood. With 459 healthy middle-class women between 18 and 67 years (x = 41.5) the association between age at menarche and body composition was tested. Body composition, described by absolute and relative amount of fat mass, lean body mass, and bone mass, was estimated by means of dual energy x-ray absorptiometry. In order to exclude the influence of the menopausal transition on body composition, pre- and postmenopausal females were examined separately. The absolute amount of body fat was significantly lower within the group of women whose menarche occurred later. However, postmenopausal females exhibit less significant relations between the two trait systems than premenopausal women. This may be due to the impact of menopausal transition which affected the hormone levels and body composition development independently from the adolescent hormonal transition. While in both proband groups the quantitative amount of body fat was significantly related to menarcheal age, a significant relation between menarcheal age and adult body fat distribution could not be verified.

Adolescent↗