PubMed Health⌕ Search

Biomedical subjects

B Gruber

Publications and source records attributed to B Gruber.

At least 19 recordsLinked to original sources
PubMed2006

Homocysteine but not neopterin declines in demented patients on B vitamins.

Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Hyperhomocysteinemia is common in various forms of dementia, and a significant relationship was found between concentrations of homocysteine and immune activation marker neopterin. B vitamin supplementation is able to slow-down homocysteine formation in patients. In an open-label study, effects of B vitamin supplementation (Beneuran compositum ) on concentrations of homocysteine and neopterin were investigated in 58 patients with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive impairment (n=16). In all groups of patients, a significant percentage of patients presented with homocysteine concentrations >15 micromol/L and with elevated concentrations of immune activation marker neopterin. Decline of homocysteine concentrations was observed after one month of B vitamin supplementation (all p<0.01; paired Kruskal-Wallisn-test). By contrast, neopterin concentrations remained unchanged (all p>0.05). B vitamin supplementation in patients with various forms of dementia did not influence neopterin concentrations, which indicates that the degree of immune activation and inflammation remained unchanged. The question remains, if lowering of homocysteine by folate supplementation alone could have any beneficial effect to modulate the course of dementia development and if longer period of supplementation would also ameliorate immune system activation status.

Dementia↗
PubMed2001

[Intrapulmonary tumor cell embolism from cancer of the bladder as the cause of a subacute cor pulmonale].

HISTORY AND CLINICAL FINDINGS: A 61-year-old man had over 3 weeks experienced increasing dyspnoea on effort and loss of appetite. He reported previous chronic pain with a "stiffened hip" treated long-term with diclofenac, and three transurethral surgical interventions. It was only at the latest admission that bladder cancer (first diagnosed 2 years previously) became known as the reason for the interventions. On admission pallor, sinus tachycardia, fever of 38 degrees C and dyspnoea on light exertion were noted, but blood pressure was normal. INVESTIGATIONS: Chest X-ray was normal, but the patient had marked respiratory insufficiency (pO2 30.8 mmHg, pCO2 31.6 mmHg) on room air. Echocardiography showed a dilated right ventricle with paradoxical septal movement. There was no evidence of thrombosis in the leg veins on ultrasound. D-dimers were normal. DIAGNOSIS, TREATMENT AND COURSE: Pulmonary artery embolism of unknown origin was suspected. Despite anticoagulation with low-molecular heparin the patient's condition deteriorated. Spiral computed tomography of the thorax did not show thrombi in the pulmonary arterial vessels. Perfusion scintigraphy demonstrated definite perfusion deficits bilaterally in the upper lobes of the lung, consistent with pulmonary embolism. As his condition gradually worsened rt-PA was started to achieve fibrinolysis, but failed to produce any change in haemodynamic and respiratory functions. He died a few hours later. Microscopic examination at autopsy revealed multiple tumour emboli with intimal fibrosis in the peripheral arteries. A poorly differentiated urothelial carcinoma of the bladder with extensive infiltration of blood vessels was found (carcinomatous haemangiosis). CONCLUSION: A malignant tumour with micro-embolization of tumour cells should be considered as a possible diagnosis when the clinical picture indicates pulmonary embolism of unknown genesis.

Carcinoma, Transitional Cell↗
PubMed2000

MCR XVI. Mathematical support for combinatorial chemistry

The algebra of the s- and r-vectors is an adequate formal tool to describe chemical objects in an abstract way. Compounds as well as reactions are represented, including all constitutional and configurational aspects. The stereochemistry of simple organic molecules as well as those of metal-organic compounds may be described in a unique way. Ionic bonds, covalent bonds, aromatics, and electron-deficiency compounds can formally be described without loss of information. Even reaction types and the flow of electrons can be described by this algebra. The biggest benefit of this approach is its intrinsic group theoretical structure. This does not bother the chemist for its use but allows a computer to handle and structure huge amounts of chemical data. This is especially important for combinatorial chemistry, which deals with huge sets of chemically distinct molecules, the so-called molecular libraries.

Journal Article↗
PubMed1998

Induction of arachidonic acid metabolite release by human fibroblasts in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is a severe ocular disorder characterized by unwanted proliferation of cells and excessive production of fibrous tissue, which leads to the formation of cellular membranes on the surface of the retina and in the vitreous. Proliferative vitreoretinopathy is the most common cause of failure in retinal reattachment surgery, approximately occurring in one out of ten operated eyes. Proliferation of retinal pigment epithelial cells and fibroblasts is a cornerstone in the pathogenesis of proliferative vitreoretinopathy. An in vitro-proliferation assay showed previously that intraocular fluid from patients with proliferative vitreoretinopathy is potently effective in stimulating proliferation of human fibroblasts. Here we show that exposure of human fibroblasts to vitreous fluids from patients with proliferative vitreoretinopathy causes a rapid and sustained increase in arachidonic acid metabolite release as measured by competitive enzyme-immunoassay. The findings implicate prostaglandin E2 as a contributor to enhanced intraocular fibrosis in proliferative vitreoretinopathy. As prostaglandin E2 is a mediator of continuous aqueous-blood retinal barrier breakdown in this severe disease, cycclooxygenase inhibitors such as acetylsalicylic acid, which was successfully used in this study for blocking the effect of intraocular fluid, may be useful agents in targeting the progression of intraocular fibrosis.

Adult↗
PubMed1998

Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the efficacy and tolerability of an oral preparation of iloprost, a prostacyclin analog, in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma). METHODS: A multicenter, randomized, parallel-group, placebo-controlled double-blind study was performed at university and community-based medical centers. Patients were randomly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks. Outcome measures included average total daily duration of RP attacks, average number of RP attacks, and RP condition scored via a standardized daily diary. RESULTS: Three hundred eight patients with scleroderma (272 women, 36 men, mean age 49 years [range 18-80]) were enrolled. One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo. One hundred forty-three patients in the iloprost group (91.1%) and 144 in the placebo group (95.4%) completed the 6-week treatment phase. Fifteen of these treated patients (8 iloprost, 7 placebo) failed to complete all of the followup visits. The mean reduction in the average duration of attacks from baseline to week 5-6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group (P = 0.569). Likewise, the mean reduction from baseline to week 5-6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group (P = 0.459). The Raynaud's condition score, a patient-completed assessment of the severity of RP attacks, was reduced by 1.32 in the iloprost group and 1.00 in the placebo group (P = 0.323). The lack of significant difference between treatment groups did not change when a variety of factors, including use of other vasodilators, duration of disease, classification of scleroderma (limited versus diffuse), or number of baseline digital ulcers were taken into account. Premature withdrawal from the study due to adverse events occurred in 10 patients (6.4%) in the iloprost group and 3 (2.0%) in the placebo group (P = 0.058). CONCLUSION: Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma, either during 6 weeks of treatment or during 6 weeks of posttreatment followup.

Administration, Oral↗
PubMed1998

Mutational analysis of the tumor suppressor Smad2 in acute lymphoid and myeloid leukemia.

Smad4 is a tumor suppressor that is inactivated in about 50% of pancreatic carcinomas. Mutations in this gene have also been found with variable, yet much lower frequency in other tumor types and were absent from a large number of samples from patients with hematological malignancies. Smad2 shows considerable sequence similarity with Smad4 and cooperates with it in the growth inhibitory TGF-beta pathway. Smad2 mutations have been found in a fraction of colon carcinomas and have been shown to impair the function of the corresponding proteins. However, only a few other tumor types have been screened for Smad2 mutations so far. Therefore, we analyzed 50 primary tumor samples from patients with acute lymphoid or myeloid leukemia (ALL or AML) and five cell lines of hematopoietic origin for alterations in the Smad2 gene. None of the specimens tested carried mutations in the conserved MH1 or MH2 domains of Smad2.

Base Sequence↗
PubMed1998

Sarcoidosis of the external nose mimicking rhinophyma. Case report and review of the literature.

A 52-year-old man with a large external nasal mass is presented. Initially, the mass was thought to be rhinophyma, but biopsy of the mass revealed noncaseating granulomata consistent with sarcoidosis. The mass resolved following several steroid injections. The case is discussed in detail, along with a review of the literature pertaining to sarcoidosis of the nose and nasal cavity.

Diagnosis, Differential↗
PubMed1997

Staurosporine-dependent activation of human endothelial cell monolayers for neutrophil adherence by secretoneurin.

Functions of secretoneurin include chemotaxis for monocytes and endothelial cells, and inhibition of endothelial cell proliferation. Inhibition of monocyte chemotaxis by staurosporine indicated involvement of specific signaling mechanisms. We have tested effects of kinase inhibitors on activation of endothelial cells for neutrophil adherence by secretoneurin. Pretreatment of endothelial cells by secretoneurin induced in endothelium increased adhesiveness to neutrophils. Addition of staurosporine, an inhibitor of protein kinase C, completely abolished endothelial cell activation, whereas tyrphostin-23, a tyrosin kinase inhibitor, had no effect. Results on activation of neutrophil-endothelial cell adherence by secretoneurin demonstrate that specific signaling mechanisms are involved in endothelial cell activation.

Cell Adhesion↗
PubMed1997

Effect of sex and age on bone mass, body composition and fuel metabolism in humans.

The mechanism(s) governing the gain of upper-body fat and its relationship to the decrease in bone mass with age is still unclear. Therefore, four groups of subjects matched for weight, height, and body mass index (n = 119; 60 women, 59 men), but differing in age (above and below 50 y) and sex were investigated using dual energy x-ray absorptiometry (DXA) to assess body composition (bone, lean, and fat mass as well as its distribution) and indirect calorimetry to determine resting fuel metabolism. Fat mass of trunk and arms (P < 0.01), but not legs, increased with advancing age in males, resulting in a continuous increase in the ratio of upper- to lower-body fat (r = 0.45, P < 0.001). In contrast, total fat mass remained stable in women, irrespective of menopause, but a redistribution of fat occurred with advancing age (r = 0.43, P < 0.001), resulting in a higher upper- to lower-body fat ratio (P < 0.05) in older than in younger women. Total lean soft-tissue mass of all segments of the body was greater in men than in women irrespective of age (P < 0.001), and lower in the older groups than in the younger ones irrespective of sex. In males, but not females, lean soft-tissue mass in arms and legs decreased (r = 0.57, P < 0.001), whereas the ratio of total fat to lean soft-tissue mass increased (r = 0.53, P < 0.001) with age. Bone mineral content correlated with total body fat in both groups of women and in young males (r > 0.5, P < 0.001), but not in older males. With advancing age, the proportion of lean soft-tissue mass occupied by total skeleton declined in women (n = 59, P < 0.001), but remained stable in males. Resting energy expenditure decreased with age in both sexes. Protein and carbohydrate oxidation were similar in all four groups of subjects. Total fat oxidation and fat oxidation per kilogram of lean soft-tissue mass decreased with age (r > 0.36, P < 0.01) in males, but not in females, whereas it increased with increasing fat mass in females (r > 0.32, P < 0.03), but not in males. In contrast, fat oxidation per kilogram of fat mass decreased with fat mass in males (r = 0.61, P < 0.001), but not in females. Our results suggest that aging affects body composition and fuel metabolism differently in each gender, leading to reduced fat oxidation and accumulation of upper-body fat with loss of striated muscle in men, and to an increased ratio of upper- to lower-body fat and bone loss in women, the latter depending on fat mass.

Absorptiometry, Photon↗
PubMed1997

Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors.

The pRB cell cycle regulatory cascade is frequently perturbed in neoplasia by overexpression of a component of the pRB-phosphorylating cyclin D1/CDK4 complex or by inactivation of pRB or the CDK4 inhibitors p16 and p15. We investigated the status and expression of p16, p15, CCND1, CDK4 and RB genes in the Ewing family of tumors. P16 loss was observed in 8 of 27 tumors (30%) and in 12 of 23 (52%) tumor cell lines from unrelated patients. There were no discrepancies in the p16 status between primary tumors and the corresponding cell lines and between cell lines established from consecutive tumor samples. p15 was codeleted in most cases but p15 mRNA was absent also in cell lines retaining the gene. In addition, posttranscriptional p16 inactivation was observed in two cases. Although no evidence for CDK4 or CCND1 amplification was obtained, expression of these genes varied considerably in the cell lines in a case specific manner. In wild-type p16 cell lines, pRB expression was lost in one case. Our data indicate that, despite the absence of cytogenetically detectable 9p21 chromosomal aberrations, p16 deletions constitute the most frequent secondary molecular aberration in Ewing tumors so far. These results are discussed in the context of the stage of disease and the clinical outcome of the patients. The potential prognostic impact of these findings remains to be further evaluated.

Cell Cycle↗
PubMed1996

Stimulation of human skin fibroblast migration by the neuropeptide secretoneurin.

Fibroblasts, besides other cells, are called upon when tissue sustains an immunological, mechanical or chemical injury. Fibroblasts migrate into the site of inflammation, proliferate and synthesize and remodel a new matrix. These cellular responses are mediated locally by the release of neuropeptides from sensory nerve endings. Secretoneurin is a newly discovered 33-amino acid neuropeptide derived from secretogranin II (chromogranin C), which is found in sensory afferent C-fibers. We show here that secretoneurin triggers the selective migration of human skin fibroblasts in vitro, but does not stimulate their proliferation. The attraction of human skin fibroblasts toward secretoneurin could be blocked by specific anti-secretoneurin antibodies and is mediated by the C-terminal fragment of the peptide. The observed activity of this sensory neuropeptide is the first description of a specific effect on human skin fibroblasts and suggests a role for secretoneurin in inflammation and wound healing.

Antibodies↗
PubMed1996

Mobilization of tumour cells during biopsy in an infant with Ewing sarcoma.

UNLABELLED: Ewing sarcoma and the closely related peripheral primitive neuroectodermal tumour, recently referred to as Ewing tumour (ET), are characterised by unique gene rearrangements on chromosome 22. The breakpoints have been cloned and shown to fuse the Ewing sarcoma gene to one of two closely related ETS proto-oncogens, FLI-1 or ERG, which reside on chromosomes 11 and 21, respectively. The rearrangement results in the expression of specific hybrid transcripts which can be detected with high sensitivity by the reverse transcriptase polymerase chain reaction technique (RT-PCR) in primary tumours, blood and bone marrow. We report on a 7-month-old boy with a pelvic Ewing sarcoma in whom circulating tumour cells were identified in the peripheral blood during open tumour biopsy by RT-PCR. However, before and 6 days after surgery no tumour cells could be detected in the peripheral blood. CONCLUSION: The application of RT-PCR to monitor shedding of tumour cells during surgical intervention will help to evaluate if open biopsy potentially contributes to metastatic tumour cell spread.

Base Sequence↗
PubMed1996

Total tracheobronchial thrombosis due to extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is widely used for neonatal respiratory failure that is potentially reversible but unresponsive to conventional management. Because of the anticoagulation necessary for maintaining the extracorporeal circuit, hemorrhagic complications occur in up to one third of patients. We present an unusual and previously unreported complication of ECMO, total tracheobronchial thrombosis. The thrombus filled the entire lower respiratory tract and resulted in airway obstruction and inability to ventilate. The airway was successfully managed with repeated bronchoscopic pulmonary toilet. Our experience and review of the literature provide a summary of ECMO-related complications likely to present to the otolaryngologist, and management strategies are discussed.

Airway Obstruction↗
PubMed1995

Detection of tumour cells in peripheral blood and bone marrow from Ewing tumour patients by RT-PCR.

The Ewing family of tumours (ET) is characterised at the cytogenetic level by unique chromosome 22 rearrangements. The breakpoints have been cloned and were shown to fuse the EWS gene on chromosome 22 to one of two closely related ETS proto-oncogenes, FLI-I or ERG, which reside on chromosomes II and 21, respectively. The rearrangement results in the expression of chimaeric transcripts, which can be identified by means of reverse transcriptase-polymerase chain reaction (RT-PCR). We applied this method for the monitoring of ET cells circulating in the peripheral blood or infiltrating the bone marrow. The presence of tumour cells could be detected with a sensitivity of I in I x 10(6) nucleated cells. When samples were kept at 4 degrees C, tumour cells could still be identified after 48 hr of storage. Positive RT-PCR signals originated from intact ET cells rather than from free RNA released by ruptured tumour cells. We analysed peripheral blood, bone marrow samples and peripheral blood stem cell collections from 16 ET patients. At diagnosis, bone marrow specimens collected from 6 patients and I peripheral blood specimen tested positive for EWS chimaeric RNA. During therapy tumour cells were detected in bone marrow aspirations obtained from 2 patients. Our results show that ET cells infiltrating the bone marrow or circulating in peripheral blood can be identified by RT-PCR. The clinical implications for the presence of ET cells in samples detected by RT-PCR at diagnosis and during therapy requires further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva.

We previously reported that low-dose doxycycline (DOXY) therapy reduces host-derived collagenase activity in gingival tissue of adult periodontitis (AP) patients. However, it was not clear whether this in vivo effect was direct or indirect. In the present study, inflamed human gingival tissue, obtained from AP patients during periodontal surgery, was extracted and the extracts partially purified by (NH4)2SO4 precipitation. The extracts were then analyzed for collagenase activity using SDS-PAGE/fluorography/laser densitometry, and for gelatinase activity using type I gelatin zymography as well as a new quantitative assay using biotinylated type I gelatin as substrate. DOXY was added to the incubation mixture at a final concentration of 0-1000 microM. The concentration of DOXY required to inhibit 50% of the gingival tissue collagenase (IC50) was found to be 16-18 microM in the presence or absence of 1.2 mM APMA (an optimal organomercurial activator of latent procollagenases); this IC50 for DOXY was similar to that exhibited for collagenase or matrix metalloproteinase (MMP)-8 from polymorphonuclear leukocytes (PMNs) and from gingival crevicular fluid (GCF) of AP patients. Of interest, Porphyromonas gingivalis collagenase was also inhibited by similar DOXY levels (IC50 = 15 microM), however the collagenase activity observed in the gingival tissue extracts was found to be of mammalian not bacterial origin based on the production of the specific alpha A (3/4) and alpha B (1/4) collagen degradation fragments. In contrast, the inhibition of collagenase purified from culture media of human gingival fibroblasts (MMP-1) required much greater DOXY levels (IC50 = 280 microM). The predominant molecular forms of gelatinolytic activity presented in the AP patients gingival tissue extracts were found to closely correspond to the 92 kD PMN-type gelatinase (MMP-9) although small quantities of 72 kD fibroblast-type gelatinase (MMP-2), and some other low molecular weight gelatinases, were also detected. The IC50 of DOXY versus gingival tissue gelatinolytic activity was estimated at 30-50 microM measure using either type I gelatin zymography or the biotinylated type I gelatin assay. We conclude that MMPS in inflamed gingival tissue of AP patients, like those in GCF, originate primarily from infiltrating PMNs rather than resident gingival cells (fibroblasts and epithelial cells) or monocyte/macrophages, and that their pathologically-elevated tissue-degrading activities can be directly inhibited by pharmacologic levels of doxycycline.

Adult↗
PubMed1994

Differential NPY mRNA expression in granule cells and interneurons of the rat dentate gyrus after kainic acid injection.

Using in situ hybridization histochemistry neuropeptide Y (NPY) mRNA expression was investigated after intraperitoneal injection of kainic acid (KA) and after local application of KA or quinolinic acid into the dentate gyrus of the rat. Enhanced concentrations of NPY mRNA were observed in interneurons of the hilus, including presumptive fusiform neurons and pyramidal-shaped basket cells already 4 hours after initiation of limbic seizures by KA (10 mg/kg, i.p.). Increased NPY expression persisted in neurons resistant to seizure-induced cell death (6-48 h after i.p. KA). Exceptionally high hybridization signals were found in interneurons of the hilus and the CA1 and CA3 sectors 8 months after KA-induced limbic seizures. In the granule cell layer only a transient but pronounced increase in NPY mRNA was observed 12-24 h after injection. Only moderate changes were observed in this cell layer at later intervals. Anticonvulsant treatment with thiopental, after a brief period of generalized seizures, prevented the increase in NPY mRNA in granule cells but not in interneurons. No change in NPY message was found also in granule cells of rats which responded with mild "wet dog shake" behavior but not with motor seizures to KA injection. Local injections of low doses of KA (0.05-0.2 nmol) or quinolinic acid (6.5-100 nmol) into the dentate gyrus of the hippocampus under deep thiopental anesthesia, after 24 h, resulted in increased concentrations of NPY message in interneurons of the ipsilateral, but not of the contralateral hilus and not in granule cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Leiomyoma of the tongue presenting as congenital airway obstruction.

Leiomyoma is a benign tumor of smooth muscle origin that is most commonly found in the uterus, gastrointestinal tract, and skin. Intraoral leiomyomas are rare, usually asymptomatic, and, most often present in the fifth decade of life. A review of the literature since 1884 yielded only 125 cases, including 23 of the tongue. We report the first case of a congenital leiomyoma of the tongue presenting with airway obstruction. A 6-day-old female infant, intubated since birth for respiratory distress, was evaluated for an obstructing oropharyngeal mass. The tumor was pedunculated, mucosa-covered, and localized to the posterior tongue. The mass was completely excised using a CO2 laser. There has been no recurrence in 1 year of follow-up.

Airway Obstruction↗