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Biomedical subjects

A Sommer

Publications and source records attributed to A Sommer.

At least 73 records · Page 4Linked to original sources
PubMed1999

The relationship between optic disc area and open-angle glaucoma: the Baltimore Eye Survey.

PURPOSE: To determine if eyes with larger optic disc area are more likely to have open-angle glaucoma or to have glaucoma at lower intraocular pressure (IOP). METHODS: Data were collected from a population-based sample of adults residing in East Baltimore, consisting of demographic information, ocular examinations, automated and static/kinetic visual field tests, IOP as measured by applanation tonometry, and image analysis of the optic disc. Optic disc area was calculated using refractive error to correct magnification. Open-angle glaucoma was defined by visual field and optic disc criteria. One eye from each of 75 patients with glaucoma was compared to those of 3,518 subjects without glaucoma. RESULTS: Although optic disc area was somewhat larger among patients with glaucoma than control subjects, in a regression model adjusting for age, gender, and race, the significance of this difference had a probability of 0.06. Among patients with glaucoma, disc area was not related to IOP level measured at study examination. CONCLUSION: Disc area is a weak risk factor for open-angle glaucoma. Disc area did not differ between patients with glaucoma who had lower IOP and those who had higher IOP among a group with glaucoma that were identified in a population survey.

Adult↗
PubMed1998

Purification and properties of a novel chloroplast stromal peptidase. Processing of polyphenol oxidase and other imported precursors.

Polyphenol oxidases (PPOs) are nuclear-encoded chloroplast proteins that are targeted to the thylakoid lumen by a bipartite presequence. The N-terminal part of this sequence is removed by a stromal processing peptidase (SPP), and the resulting intermediate is translocated across the thylakoid and processed to the mature protein. A 4800-fold-purified SPP processed a PPO precursor (pPPO) at a site identical to that occurring in organelle. The in vitro product of SPP action on pPPO was further processed and translocated by thylakoids. This SPP processed other precursors but was inactive toward those of light-harvesting chlorophyll binding proteins. The enzyme appeared to be a metalloendopeptidase, like previously reported SPPs. However, it differed in substrate specificity, apparent size, and, most significantly, cleavage site of pPPO. Whereas the processing sites of lumen proteins determined so far were relatively distant from the hydrophobic core of the thylakoid targeting domain, pPPO was cleaved immediately before this domain. Cleavage removed the twin arginine motif characteristic of thylakoid targeting domains of lumen proteins, which are translocated by the DeltapH-dependent pathway. The possible significance of these observations to PPO translocation mechanism is discussed. It is suggested that several SPPs may exist in chloroplasts with preferences for different subsets of precursors.

Amino Acid Sequence↗
PubMed1998

Identification and characterization of specific DNA-binding complexes containing members of the Myc/Max/Mad network of transcriptional regulators.

In the past, eukaryotic cell-derived complexes of the Myc/Max/Mad network of transcriptional regulators have largely been refractory to DNA binding studies. We have developed electrophoretic mobility shift assay conditions to measure specific DNA binding of Myc/Max/Mad network complexes using a COS7 cell-based overexpression system. With the established protocol, we have measured on- and off-rates of c-Myc/Max, Max/Max, and Mad1/Max complexes and determined relative affinities. All three complexes appeared to bind with comparable affinity to a Myc E-box sequence. Furthermore, our data derived from competition experiments suggested that the Mad3/Max and Mad4/Max complexes also possess comparable DNA binding affinities. The conditions established for COS7 cell-overexpressed proteins were then used to identify c-Myc/Max, Max/Max, and Mnt/Max complexes in HL-60 cells. However, no Mad1/Max could be detected, despite the induction of Mad1 expression during differentiation. Whereas the DNA binding activity of c-Myc/Max complexes was down-regulated, Max/Max binding increased, and Mnt/Max binding remained unchanged. In addition, we have also tested for upstream stimulatory factor (USF) binding and observed that, in agreement with published data, USF comprises a major Myc E-box-binding factor that is more abundant than any of the Myc/Max/Mad network complexes. Similar to the Mnt/Max complex, the binding activity of USF remained constant during HL-60 differentiation. Our findings establish conditions for the analysis of DNA binding of Myc/Max/Mad complexes and indicate posttranslational regulation of the Max/Max complex.

Animals↗
PubMed1998

Spontaneous healing of cervical pseudoaneurysm in vertebral artery dissection under anticoagulant therapy.

We report a 41-year-old woman with embolic stroke of the mid-pons attributed to embolism from vertebral artery dissection. Angiography revealed an occluded artery on one side and an incidental pseudoaneurysm of the midcervical portion of the vertebral artery on the other. After 3 months of warfare in therapy control angiography showed complete occlusion of the pseudoaneurysm. We discuss therapeutic choices and review the literature.

Adult↗
PubMed1998

Xerophthalmia and vitamin A status.

The existence of 'fat-soluble A' has been known for over 80 years. But until recently clinicians were almost wholly absorbed by the ocular changes accompanying deficiency (xerophthalmia), and scientists with the vitamin's metabolic role in the rhodopsin cycle. The past two decades have witnessed a revolution in clinical and scientific concerns. Xerophthalmia is now recognized as a late manifestation of severe deficiency rather than of early, mild deficiency; as the mechanism responsible for half or more of all measles-associated blindness; and as the cause of half a million or more cases of pediatric blindness worldwide. Milder deficiency increases the severity of infectious morbidity, exacerbates iron deficiency anemia, retards growth, and is responsible for one to three million childhood deaths each year. Scientists are now busy unraveling vitamin A-dependent gene regulation to explain the myriad manifestations accompanying deficiency, while clinicians are designing and supervising programs to improve vitamin A status in over 60 countries, up from only three countries two decades ago. Control of vitamin A deficiency is now a major health challenge and goal of both UNICEF and the World Health Organization (WHO). Reaching that goal requires better parameters for assessing vitamin A status, increased understanding of metabolic pathways responsible for corneal dissolution (keratomalacia) and the molecular and cellular basis by which vitamin A status mediates resistance to infection. These issues are detailed elsewhere (Sommer and West, 1996).

Animals↗
PubMed1998

Evaluation of the vasoconstrictive effects of topical steroids by laser-Doppler-perfusion-imaging.

Corticosteroids are one of the most frequently prescribed local therapeutic treatments. Their potency and bioavailability are tested with different methods. One of the most accepted methods is the skin-blanching test designed by McKenzie. In this study we investigated whether the skin-blanching test designed by McKenzie for screening topically active corticosteroids, producing vasoconstriction, is sufficiently detectable by a laser-Doppler-perfusion-imager (LDPI). Eight sites in two rows on the right forearm of 10 healthy volunteers were treated with a topical glucocorticosteroid (clobetasol-17-propionate 0.05% (Dermovate), and the bloodflow at each site was measured by the LDPI at different timesteps. Four sites per row were chosen to evaluate the dependency of bioavailability according to anatomical differences due to skin changes within the forearm. Furthermore, half of the sites were occluded to demonstrate the difference between occluded and non-occluded sites in bioavailability. The results show that the LDPI can easily detect changes in bloodflow due to the vasoconstriction caused by topical corticosteroid. The results showed significant changes during the different measurements, with a maximum reaction 30 h after the application of the corticosteroid. The sites under occlusion showed a slower decrease of laser values than those without occlusion, so that it can be pointed out that occlusion prolongs the bioavailability of corticosteroids but does not influence the speed of onset. So far we conclude that this technique is a simple and non-traumatic method for assessing steroid potency. Blanching, as a result of vasoconstriction, can be quantified by LDPI measurement. However, LDPI measurements have to be compared with other techniques, such as the non-traumatic 133Xe washout technique, to find out if the two technologies respond in a similar way.

Administration, Topical↗
PubMed1998

Double-blind trial of omeprazole and amoxicillin in the cure of Helicobacter pylori infection in gastric ulcer patients. The Ulcer Study Group, Germany.

BACKGROUND: Our aim was to investigate the efficacy of omeprazole and amoxicillin in curing Helicobacter pylori infection in gastric ulcer patients. METHODS: In a double-blind trial 185 H. pylori-positive gastric ulcer patients were prospectively randomized to receive 40 mg omeprazole twice daily and either 750 mg amoxicillin three times daily or 750 mg amoxicillin placebo three times daily on days 1-14, followed by 20 mg omeprazole daily on days 15-56. RESULTS: Twenty-seven patients were excluded because of lack of compliance or missed follow-up examinations; one patient receiving amoxicillin discontinued treatment owing to side effects. On an intention-to-treat basis, omeprazole/amoxicillin led to cure of H. pylori infection in 67.1% (47 of 70) of patients not using non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin (ASA) and in 46.7% (14 of 30) of those taking NSAIDs/ASA (P < 0.05). With the omeprazole/placebo regimen, H. pylori infection was cured in 8.8% (no NSAIDs), and 0% (NSAIDs). CONCLUSIONS: The use of NSAIDs/ASA may limit the efficacy of omeprazole/amoxicillin in curing H. pylori infection in gastric ulcer patients.

Adolescent↗
PubMed1998

Influence of dietary concentrate to forage ratio on the development of rumen mucosa in calves.

Effects of structural and non-structural carbohydrates on the development of rumen fermentation and ruminal mucosa in calves were examined during the weaning period. Barley/soybean meal (SBM) group was fed a concentrate starting from 2 weeks of age, whereas alfalfa group received a mixture of concentrate and alfalfa hay in which the proportion of the latter was gradually increased from 20% to 70% between weeks 2 and 9 of age. The total volatile fatty acid concentration in rumen fluid of calves increased with age, but at 9 weeks there were no significant differences between the two diets (barley/SBM group 153 mmol/l, alfalfa group 150 mmol/l). Rumen papillae at 9 weeks of age, as compared to 6 weeks of age, were longer and fewer in number per square centimetre mucosa, with larger cut surface. This resulted in a higher surface of papillae per square centimetre mucosa at 9 weeks (barley/SBM group 286 mm2/cm2, alfalfa group 245 mm2/cm2) than at 6 weeks of age (barley/SBM group 217 mm2/cm2, alfalfa group 198 mm2/cm2). At 9 weeks of age, the pH (barley/SBM 5.0, alfalfa 5.7), the acetate to propionate ratio (barley/SBM 2.2, alfalfa 3.2) as well as the length of the papillae in the ventral ruminal sac (barley/SBM 1.96 mm, alfalfa 2.37 mm) were increased in the alfalfa group when compared to the barley/SBM group (P < 0.1). In the former group, the proportion of butyrate revealed significantly increased values at 4 and 6 weeks of age. In animals of the barley/SBM group at 9 weeks of age, characteristic protrusions with proliferated thick epithelium occurred on the papillae and increased the surface for absorption. On the epithelium (Stratum corneum) desquamating cells with parakeratosis could be observed. In the alfalfa group the papillae of the ventral ruminal sac were longer, without protrusions. The morphotypes of the adhering rumen microflora differed between the groups. It can be concluded that feeding greater amounts of non-structural carbohydrates increases the surface for absorption of the rumen epithelium in calves. The absence of hyperkeratosis and rumenitis in the barley/SBM group indicated that there is no reason to limit high starch diets in the early weaning period of calves.

Acetic Acid↗
PubMed1998

Research note: investigation on the metabolism of glycerol in the rumen of bulls.

Two bulls, each fitted with rumen and duodenal cannulas, received (in addition to a hay-grain diet) twice daily an infusion of 200 g glycerol into the rumen over a period of six days. During this preliminary in vivo investigation, the influence of a glycerol application on the rumen environment over a six-day adaptation period was examined. Samples of rumen fluid were collected daily, two hours after glycerol infusion. An additional 15N-urea application into the rumen was given on days 1 (without glycerol infusion), 3 and 7 (with glycerol infusion). Extra samples of rumen fluid and blood plasma (from puncture of vena jungularis) were taken through the 12th hour following urea application. Rumen fluid pH was reduced due to glycerol intake from 6.3 (day 1, without glycerol) to 5.4 by day 7. Molar proportion of acetic acid to propionic acid decreased from 3.5 (day 1) to 2.1 (days 6 and 7). Average glycerol disappearance rate from the rumen was 4.7 gl-1 h-1 for the first hour. Only small amounts of glycerol could be detected in the duodenal digesta. Blood plasma glycerol content was significantly higher after glycerol application (0.061 mmol l-1 vs. 0.019 mmol l-1). The incorporation of 15N into the rumen bacteria and the proportion of bacterial N (as percent of TCA-precipitable N in the rumen fluid) were lower after glycerol influsion. These results, coupled with the lower concentration of iso-acids (isobutyric and isovaleric acids) in the rumen fluid, indicate that the high amount of glycerol infusion (10% of DMI) reduced protein metabolism of rumen bacteria throughout the experimental period.

Adaptation, Physiological↗
PubMed1998

Moving from science to public health programs: lessons from vitamin A.

The transition from research to the applications of its results is a difficult one. Several stages must be passed through before a discovery can be put to practical use. The development of the current standards for vitamin A is a good example of both a successful and a difficult transition. The importance of the public media and of international organizations, especially the World Health Organization, in any transition is noted. Movement from research to practical applications requires that scientists take an active, sensible leadership role, that mechanisms for disseminating information and for bringing about scientific consensus are used effectively, and that international funding and support agencies take a role.

Animals↗
PubMed1998

Palliation of malignant esophageal obstruction due to intrinsic and extrinsic lesions with expandable metal stents.

OBJECTIVE: Metal stents have become the standard of care for esophageal stenting. The aim of this study was to determine the safety and efficacy of metal stents for the palliation of dysphagia caused by extraesophageal malignancies compressing the esophagus, compared with that caused by intrinsic lesions involving the esophagus. METHODS: Expandable metal stents were placed in 46 consecutive patients with dysphagia caused by malignant extrinsic compression of the esophagus (n=24) and intrinsic esophageal strictures (n=22). Quality of life was determined by a dysphagia score and the Karnofsky performance scale. Patients were followed until death. RESULTS: Stents were successfully deployed in all 24 patients. Dysphagia scores improved from a median of 3 (range, 3-4; mean, 3.5+/-0.2) to a median of 2 (range, 1-4; mean, 1.6+/-0.4; p < 0.0001) in the extrinsic group, and from a median of 3 (range, 2-4) to a median of 1 (range, 1-3) in the intrinsic group (p < 0.0001). The improvement was significantly greater (p=0.01) in the intrinsic group. There was no significant difference in the Karnofsky score between the two groups. CONCLUSIONS: Patients with intrinsic lesions have better palliation of dysphagia than those with extrinsic lesions. Future studies with other study designs will need to consider this.

Aged↗
PubMed1997

Cell growth inhibition by the Mad/Max complex through recruitment of histone deacetylase activity.

BACKGROUND: The organization of chromatin is crucial for the regulation of gene expression. In particular, both the positioning and properties of nucleosomes influence promoter-specific transcription. The acetylation of core histones has been suggested to alter the properties of nucleosomes and affect the access of DNA-binding transcriptional regulators to promoters. A recently identified mammalian histone deacetylase (HD1) shows homology to the yeast Rpd3 protein, which together with Sin3 affects the transcription of several genes. Mammalian Sin3 proteins interact with the Mad components of the Myc/Max/Mad network of cell growth regulators. Mad/Max complexes may recruit mammalian Rpd3-like enzymes, therefore, directing histone deacetylase activity to promoters and negatively regulating cell growth. RESULTS: We report the identification of a tetrameric complex composed of Max, Mad1, Sin3B and HD1. This complex has histone deacetylase activity which can be blocked by the histone deacetylase inhibitors trichostatin A and sodium butyrate. The inhibition of cell growth by Mad1 is enhanced by Sin3B and HD1, as measured by colony formation assays. Furthermore, a Mad1-induced block of S-phase progression can be overcome by trichostatin A, as shown in microinjection experiments. CONCLUSIONS: The recruitment of a histone deacetylase by sequence-specific DNA-binding proteins provides a mechanism by which the state of acetylation of histones in nucleosomes and hence the activity of specific promoters can be influenced. The finding that Mad/Max complexes interact with Sin3 and HD1 in vivo suggests a model for the role of Mad proteins in antagonizing the function of Myc proteins.

Animals↗