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Biomedical subjects

B Becker

Publications and source records attributed to B Becker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lisinopril therapy for hemodialysis hypertension: hemodynamic and endocrine responses.

To evaluate the antihypertensive effects of lisinopril, a renally excreted angiotensin-converting enzyme inhibitor, we assessed supervised administration of the drug after hemodialysis (HD) three times weekly. Blood pressure (BP) was assessed by interdialytic 44-hour ambulatory BP (ABP) monitoring, and endocrine responses were assessed by plasma renin activity (PRA) before and after dialysis. Lisinopril dose was titrated at biweekly intervals. If this was not effective after full titration (lisinopril to 40 mg three times weekly), ultrafiltration was added to reduce dry weight. The primary outcome variable was change in BP from the end of the run-in period to the end of the study. No change in mean ABP was noted during run-in. However, mean 44-hour ABP decreased from 149 +/- 14 (SD)/84 +/- 9 to 127 +/- 16/73 +/- 9 mm Hg, a decrease of 22/11 mm Hg (P < 0.001) at final evaluation. Of 11 patients who completed the trial, only 2 patients had systolic hypertension (>/=135 mm Hg) and 1 patient had diastolic hypertension (>/=85 mm Hg) at the final visit. Four patients were administered 10 mg of lisinopril; 5 patients, 20 mg; and 2 patients, 40 mg; only 1 of these patients required ultrafiltration therapy. There was a persistent antihypertensive effect over 44 hours. BP reduction was achieved without an increase in intradialytic symptomatic or asymptomatic hypotensive episodes. PRA increased in response to dialysis, as well as lisinopril. In conclusion, supervised lisinopril therapy is effective in controlling hypertension in chronic HD patients. This may be related to blockade of angiotensin II generation by kidneys despite the loss of excretory function.

Adult↗
PubMed2001

Analysis of expressed sequence tags (ESTs) from the scaly green flagellate Scherffelia dubia Pascher emend. Melkonian et Preisig.

Partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of gene discovery, generation of molecular markers and characterization of transcription patterns. We have constructed an EST-database of the scaly green flagellate Scherffelia dubia (Chlorophyta) containing 361 sequences. cDNAs were obtained from interphase cells and from cells regenerating flagella. Analysis of the ESTs identified 138 EST-groups with significant similarity to known sequences. 134 EST-groups showed no significant similarity to any sequences in the databases. Most of the ESTs with similarity to known proteins are associated with typical interphase cell functions of a photosynthetic plant cell: assimilation of nutrients and biosynthesis of proteins. Others are related to the activation of the secretory pathway or the biogenesis of scales (e.g. kdo-synthase). Comparison of S. dubia ESTs with the genome of Arabidopsis thaliana and the EST database of Chlamydomonas reinhardtii revealed that S. dubia ESTs with similarity to known proteins were more similar to sequences in C. reinhardtii than to those of A. thaliana. Additionally, ESTs for guanylyl cyclase and cGMP phosphodiesterase are present in the two flagellates, but so far these gene products have not been found in embryophytes.

3' Untranslated Regions↗
PubMed2001

Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II.

Cyclooxygenase-II (Cox-II) overexpression is involved in the progression of various subtypes of cancer. We investigated the significance of Cox-II in the progression of malignant melanomas (MMs). Using immunohistology we determined that Cox-II is not expressed in 70 benign and malignant melanocytic tumours. Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were also analysed as controls: the BCCs were consistently Cox-II negative (n = 11), whereas the SCCs showed moderate to strong Cox-II expression in 53% (n = 17). Reverse transcription-polymerase chain reaction and Western blotting of MM cell lines and MM tissues confirmed the lack of Cox-II expression in MM. However, in vitro the Cox-inhibiting non-steroidal anti-inflammatory drug (NSAID) sulindac sulphide (SIS) was significantly more effective in inducing apoptosis than sulindac sulphone (SOS), a derivative with a negligible effect on Cox (P < 0.01). The SIS doses needed for the induction of apoptosis were not significantly different in MM cell lines versus a Cox-II-positive colon carcinoma cell line (HT29). Furthermore, add-back experiments with high doses of the prostaglandins PGE2 and PGF2beta, major Cox-II products, did not abrogate this effect. We conclude that Cox-II expression is not involved in the progression of MM, and NSAID-induced apoptosis in MM cell lines seems to follow pathways independent of Cox-II. Nevertheless, Cox-II inhibitors are still candidates for therapy, though they act via an unknown mechanism.

Adolescent↗
PubMed2001

Effect on insulin release of compounds structurally related to the potassium-channel opener 7-chloro-3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide (BPDZ 73): introduction of heteroatoms on the 3-alkylamino side chain of the benzothiadiazine 1,1-dioxide ring.

7-Chloro-3-pyridyl(alkyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxides and 3-alkylamino-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides containing one or more heteroatoms on the side chain in the 3 position have been synthesized in an attempt to discover new potent KATP-channel openers. The compounds were tested as putative pancreatic B-cells KATP channel openers by measuring their inhibitory activity on the insulin releasing process. The influence on the biological activity of the nature of the side chain in the 3 position is discussed.

Animals↗
PubMed2001

Evaluating the effects of a brief motivational intervention for injured drinkers in the emergency department.

OBJECTIVE: The study aim was to test whether a brief motivational intervention, with or without a booster session, would improve drinking-related outcomes more than standard Emergency Department (ED) treatment. METHOD: The study population consisted of 539 (78% male) injured patients treated in the ED and discharged to the community following their treatment. Injured patients met inclusion criteria if they were assessed as hazardous or harmful drinkers by scoring eight or more on the AUDIT and/or having alcohol in their system at the time of their injury or ED visit. Patients were randomly assigned to either standard care (SC), brief intervention (BI) or brief intervention plus a booster session (BIB). At 1-year follow-up, 447 patients (83% of the sample) were re-interviewed to measure alcohol-related negative consequences, injuries and drinking. RESULTS: Patients receiving BIB, but not B1 patients, reduced alcohol-related negative consequences and alcohol-related injuries more than did those in the SC group. All three groups reduced their days of heavy drinking. Patients with histories of hazardous drinking responded to BIB, whether or not they had consumed alcohol prior to their injury. CONCLUSIONS: Together, these results indicate that the effects of a booster session that is added to a brief intervention in the ED can be helpful to injured patients with a history of hazardous or harmful drinking, irrespective of whether they have consumed alcohol prior to their injury.

Adolescent↗
PubMed2000

Effect of latanoprost or 8-iso prostaglandin E2 alone and in combination on intraocular pressure in glaucomatous monkey eyes.

OBJECTIVE: To evaluate the possible additivity of the effects of latanoprost and 8-iso prostaglandin E2 (8-iso PGE2) on intraocular pressure (IOP) in monkey eyes with laser-induced glaucoma. METHODS: The IOP was measured hourly for 6 hours beginning at 9:30 AM on day 1 (baseline day), days 6 and 7 (single-agent therapy), and days 13 and 14 (combination therapy with both agents). Following 1 day of baseline measurement, 4 monkeys with unilateral glaucoma received monotherapy) twice daily with either 1 drop of 0.005% latanoprost, or 0.1% 8-iso PGE2, 25 microL, at 9:30 AM and 3:30 PM from days 2 through 7. From days 8 through 14, both agents were applied twice daily 5 minutes apart. RESULTS: The maximum reduction of IOP (mean +/- SEM) was 8.8 +/- 1.9 mmHg (26%) (P<.05) with latanoprost alone and 6.5 +/- 1.0 mmHg (21%) (P<.0l) with 8-iso PGE2 alone, 2 hours after the morning dosing on day 7. A further reduction of IOP of 4.0 +/- 0.6 mm Hg was produced when 8-iso PGE2 was added to latanoprost and of 3.0 +/- 0.7 mm Hg was produced when latanoprost was added to 8-iso PGE2 on day 13 before the morning dosing. Combination therapy with both agents caused maximum IOP reductions from baseline of 11.3 +/- 3.0 mm Hg (33%) (P<.05) (latanoprost with 8-iso PGE2 added) and of 9.8 +/- 1.3 mm Hg (31%) (P<.01) (8-iso PGE2 with latanoprost added) on day 14. CONCLUSION: Latanoprost and 8-iso PGE2 have an additive effect on IOP in glaucomatous monkey eyes. CLINICAL RELEVANCE: At least 50% of patients are treated with more than 1 ocular hypotensive medication. Thus, the determination of the additive effects on IOP of glaucoma medications will help to define optimum treatment regimens.

Animals↗
PubMed2000

The Golgi apparatus of the scaly green flagellate Scherffelia dubia: uncoupling of glycoprotein and polysaccharide synthesis during flagellar regeneration.

The flagella of the green alga Scherffelia dubia are covered by scales which consist of acidic polysaccharides and glycoproteins. Experimental deflagellation results in the regeneration of flagella complete with scales. During flagellar regeneration, scales are newly synthesized in the Golgi apparatus, exocytosed and deposited on the growing flagella. Flagellar regeneration is dependent upon protein synthesis and N-glycosylation, as it is blocked by cycloheximide and partially inhibited by tunicamycin. Metabolic labeling with [35S]methionine/cysteine demonstrated that scale-associated proteins were not newly synthesized during flagellar regeneration, suggesting that the proteins deposited on regenerating flagella were drawn from a pool. Quantitative immunoelectron microscopy using a monospecific antibody directed against a scale-associated protein of 126 kDa (SAP126) revealed that the pool of SAP126 was primarily located at the plasma membrane, with minor labeling of the scale reticulum and trans-Golgi cisternae, both before deflagellation and during flagellar regeneration. Since SAP126 was sequestered during flagellar regeneration into secretory vesicles together with newly synthesized scales, it is concluded that the persistent presence of SAP126 in the trans-Golgi cisternae during scale biogenesis requires retrograde transport of the protein from the plasma membrane to the Golgi apparatus.

Animals↗
PubMed2000

The transmembrane domain of murine alpha-mannosidase IB is a major determinant of Golgi localization.

Murine alpha1,2-mannosidase IB is a type II transmembrane protein localized to the Golgi apparatus where it is involved in the biogenesis of complex and hybrid N-glycans. This enzyme consists of a cytoplasmic tail, a transmembrane domain followed by a "stem" region and a large C-terminal catalytic domain. To analyze the determinants of targeting, we constructed various deletion mutants of murine alpha1,2-mannosidase IB as well as alpha1,2-mannosidase IB/yeast alpha1,2-mannosidase and alpha1,2-mannosidase IB/GFP chimeras and localized these proteins by fluorescence microscopy, when expressed transiently in COS7 cells. Replacing the catalytic domain of alpha1,2-mannosidase IB with that of the homologous yeast alpha1,2-mannosidase and deleting the "stem" region in this chimera had no effect on Golgi targeting, but caused increased cell surface localization. The N-terminal tagged protein lacking a catalytic domain was also localized to the Golgi. In the latter case, when the stem region was partially or completely removed, the protein was found in both the ER and the Golgi. A chimera consisting of the alpha1,2-mannosidase IB N-terminal region (cytoplasmic and transmembrane domains plus 10 amino acids of the "stem" region) and GFP was localized mainly to the Golgi. Deletion of 30 out of 35 amino acids in the cytoplasmic tail had no effect on Golgi localization. A GFP chimera lacking the entire cytoplasmic tail was found in both the ER and the Golgi. These results indicate that the transmembrane domain of alpha1,2-mannosidase IB is a major determinant of Golgi localization.

Animals↗
PubMed2000

Flagellar membrane proteins of Tetraselmis striata butcher (Chlorophyta).

Highly purified flagella of the green alga Tetraselmis striata (Chlorophyta) were extracted by Triton X-114 phase partitioning. SDS-PAGE analysis revealed that most proteins were present in the aqueous phase, only two prominent flagellar membrane proteins (fmp) of apparent molecular weight 145 and 57 kDa (fmp145 and fmp57) were enriched in the detergent phase. Fmp145 was purified by gel permeation chromatography. Glycosidase treatment in combination with lectin blot analysis showed that fmp145 is a glycoprotein containing 3-5 N-glycans of the high mannose and/or hybrid type. A polyclonal antibody (anti-fmp136) was raised against the deglycosylated form of fmp145 and used to localize fmp145 by immunofluorescence and immunoelectron microscopy. Immunogold labeling showed fmp145 to be present between the scale layers and the flagellar membrane. During flagellar regeneration fmp145 is incorporated evenly and rapidly into the newly developing flagella. Anti-fmp136 specifically cross-reacted with flagella of only a subgroup of Tetraselmis strains characterized by a specific flagellar hair type (type II according to Marin et al. 1993) and thus could be a useful immunomarker for the identification of Tetraselmis strains by fluorescence microscopy.

Algal Proteins↗
PubMed2000

Middle fossa approach in vestibular schwannoma surgery. Postoperative hearing preservation and EEG changes.

When the middle fossa (MF) approach was introduced in Denmark, we were concerned about the possible risk to the temporal lobe caused by the retraction of the lobe when exposing the internal acoustic meatus. EEG recordings were therefore obtained prospectively before (21 patients) and after MF tumor removal (all 23 patients operated from 1989 to 1997). Only three patients had normal EEG recordings before and after surgery, while 86% had induction, or worsening, of focal and paroxystic activity, even at the last follow-up (median 3.5 years). Sixteen patients operated prospectively via the translabyrinthine (TL) also had pre- and postoperative EEG and served as a control group. Only minor EEG changes were found in this group. In neither group did the patients display any clinical neurological signs (seizures). At the latest evaluation the facial function was reduced in 8 patients (35%) with 6 patients going 1 step up the scale, 1 patient 2 steps up and 1 patient 3 steps up (from HB-1 to HB-4). The integrity of the facial nerve was maintained in all patients. Postoperatively, 10 patients (44%) had useful hearing (hearing class A and B) on the operated side. Four patients had anacusis and an additional 4 patients were reduced to hearing class D with very low PTA and SDS. In total, 9 patients (39%) retained their preoperative hearing class, while 14 patients (61%) had impairment in their hearing class. In conclusion, EEG changes (low frequency activity and IEA) may be provoked or worsened as part of the middle cranial fossa procedure. The mechanism is not fully known, but may reflect peroperative pressure on the temporal lobe. EEG changes are fewer and lighter in translabyrinthine-operated patients. The practical clinical implications of the possibility of developing EEG changes, even without clinical signs, are potentially serious, and must be included in the information given to the patients before surgery.

Adult↗
PubMed2000

Smoking among emergency chest pain patients: motivation to quit, risk perception and physician intervention.

The feasibility of the emergency department (ED) as a setting for smoking interventions was examined among 159 adult patients presenting with chest pain (38% were smokers). Subjects had been admitted to a 24-h observation unit (OU) to rule out myocardial infarction. We examined the frequency and extent of physician interventions for smoking using the AHCPR guidelines as a model. We also assessed patients' perceptions of risk from smoking and motivation to quit. Results indicate that ED physicians provided incomplete and inconsistent intervention. While most patients were asked if they smoked, only half were advised to quit, and few were offered assistance with quitting. Perceived risk from smoking was low among almost half of all smokers. However, over three-quarters were willing to receive smoking cessation counseling while in the ED. The ED may be an opportune setting in which to initiate smoking cessation counseling for certain high-risk populations.

Adult↗
PubMed1999

Molecular characteristics and interactions of the intermediate filament protein synemin. Interactions with alpha-actinin may anchor synemin-containing heterofilaments.

Synemin is a cytoskeletal protein originally identified as an intermediate filament (IF)-associated protein because of its colocalization and copurification with the IF proteins desmin and vimentin in muscle cells. Our sequencing studies have shown that synemin is an unusually large member (1,604 residues, 182,187 Da) of the IF protein superfamily, with the majority of the molecule consisting of a long C-terminal tail domain. Molecular interaction studies demonstrate that purified synemin interacts with desmin, the major IF protein in mature muscle cells, and with alpha-actinin, an integral myofibrillar Z-line protein. Furthermore, expressed synemin rod and tail domains interact, respectively, with desmin and alpha-actinin. Analysis of endogenous protein expression in SW13 clonal lines reveals that synemin is coexpressed and colocalized with vimentin IFs in SW13.C1 vim+ cells but is absent in SW13.C2 vim- cells. Transfection studies indicate that synemin requires the presence of another IF protein, such as vimentin, in order to assemble into IFs. Taken in toto, our results suggest synemin functions as a component of heteropolymeric IFs and plays an important cytoskeletal cross-linking role by linking these IFs to other components of the cytoskeleton. Synemin in striated muscle cells may enable these heterofilaments to help link Z-lines of adjacent myofibrils and, thereby, play an important role in cytoskeletal integrity.

Actinin↗
PubMed1999

Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma.

Glaucoma is an optic neuropathy with cupping of the optic disk, degeneration of retinal ganglion cells, and characteristic visual field loss. Because elevated intraocular pressure (IOP) is a major risk factor for progression of glaucoma, treatment has been based on lowering IOP. We previously demonstrated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads from human glaucomatous eyes and from rat eyes with chronic, moderately elevated IOP. Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor of NOS-2, and compared them with an untreated group. At 6 months, untreated animals had pallor and cupping of the optic disks in the eyes with elevated IOP. Eyes of aminoguanidine-treated animals with similar elevations of IOP appeared normal. We quantitated retinal ganglion cell loss by retrograde labeling with Fluoro-Gold. When compared with their contralateral control eyes with normal IOP, eyes with elevated IOP in the untreated group lost 36% of their retinal ganglion cells; the eyes with similarly elevated IOP in the aminoguanidine-treated group lost less than 10% of their retinal ganglion cells. Pharmacological neuroprotection by inhibition of NOS-2 may prove useful for the treatment of patients with glaucoma.

Animals↗
PubMed1999

Role for myelin-associated glycoprotein as a functional tenascin-R receptor.

The expression of the immunoglobulin superfamily member myelin-associated glycoprotein (MAG) and the extracellular matrix glycoprotein tenascin-R (TN-R) by oligodendrocytes overlaps in time and space. The two molecules can be neurite outgrowth-inhibitory or -promoting depending on the neuronal cell type and the environment in which they are presented. Here we show that the two molecules directly bind to each other in vitro and that binding sites on TN-R localize to two domains, the fibrinogen domain and the epidermal growth factor-like repeat domain with the N-terminal cysteine-rich stretch. We further show by a functional assay, namely the repulsion of MAG-transfected Chinese hamster ovary cells (CHO) cells from a TN-R substrate, that MAG is part of the signalling pathway of TN-R for cell repulsion. When coated as a uniform substrate, MAG was inhibitory for neurite outgrowth of hippocampal and cerebellar neurons in vitro, when compared to poly-L-lysine, while TN-R enhanced neurite outgrowth. When added to MAG, TN-R neutralized the neurite outgrowth-inhibitory effects of MAG, presumably by blocking the neurite outgrowth-inhibitory domain of MAG.

Animals↗
PubMed1999

A simple synthesis of 8-(methoxycarbonyl)octyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside and derivatives and their use in the preparation of neoglycoconjugates.

8-(Methoxycarbonyl)octyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside (10) was synthesized in 54% yield by regioselective diglycosylation of unprotected mannoside 4, employing the trichloroacetimidate donor 1, followed by debenzoylation. Derivatives of compounds 4 and 10 were used to prepare conjugates containing fluorochromes for the study of carbohydrate-lectin interactions, as well as conjugates with phospholipids for the preparation of liposomes.

Carbohydrate Sequence↗
PubMed1999

V-ATPase is a major component of the Golgi complex in the scaly green flagellate Scherffelia dubia.

Highly purified membranes isolated from the Golgi complex of the scaly green flagellate Scherffelia dubia (Chlorophyta) were subjected to Triton X-114 two-phase partitioning. Proteins in the detergent phase were analyzed by 2D gel electrophoresis and a major protein of 66 kD (p66) was N-terminally sequenced. The complete cDNA sequence of p66 was obtained by 3' RACE-PCR and screening of a cDNA library of S. dubia with a PCR probe derived from the 3' RACE. Sequence analysis of the cDNA clone identified p66 as subunit A of V-ATPase. Other major proteins in the isolated Golgi complex were immunoreactive to heterologous antibodies raised against subunit B or the holoenzyme of V-ATPase. A polyclonal (anti-p66) antibody raised against a recombinant, bacterially expressed p66 fusion protein recognized p66 in the isolated Golgi complex in western blots and localized the antigen by immunogold electron microscopy mostly to the scale reticulum but also to the Golgi stack within the Golgi complex. Concanamycin A-sensitive (but bafilomycin A1-insensitive) ATPase activity was present in the isolated Golgi complex, and monensin at 0.5-1 microM reversibly inhibited flagellar regeneration and resulted in swelling of Golgi cisternae. It is concluded that a functional V-ATPase is a major protein of the Golgi complex in S. dubia and is presumably associated with sorting processes at the endocytotic/exocytotic boundary of the Golgi complex.

Amino Acid Sequence↗