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Biomedical subjects

O Frank

Publications and source records attributed to O Frank.

At least 19 recordsLinked to original sources
PubMed1998

Protein footprinting reveals specific binding modes of a high mobility group protein I to DNAs of different conformation.

The high mobility group proteins I and Y (HMGI/Y) are abundant components of chromatin. They are thought to derepress chromatin, affect the assembly and activity of the transcriptional machinery, and associate with constitutive heterochromatin during mitosis. HMGI/Y protein molecules contain three potential DNA-binding motifs (AT-hooks), but the extent of contacts between DNA and the entire protein has not been determined. We have used a protein-footprinting procedure to map regions of the Chironomus HMGI protein molecule that are involved in contacts with DNA. We find that in the presence of double-stranded DNA all AT-hook motifs are protected against hydroxyl radical proteolysis. In contrast, only two motifs were protected in the presence of four-way junction DNA. Large regions that flank the AT-hook motifs were found to be strongly protected against proteolysis in complexes with interferon-beta promoter DNA, suggesting amino acid residues outside the AT-hooks considerably contribute to DNA binding.

Animals↗
PubMed1998

Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease.

OBJECTIVE: We wanted to know if alterations in plasma cobalamin (B12) concentration and B12 carriers, e.g., holotranscobalamins (holo TC), occur in blood and liver tissue from patients with severe alcoholic liver disease. Our purpose was to test the hypothesis that liver disease may disrupt B12 distribution. METHOD: Total B12, as well as B12 bound to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas malhamensis--a protozoan reagent served to measure only metabolically active (true) B12. Total B12 as distributed in holo TC in plasma and liver tissue of healthy subjects (controls) were compared to patients with severe alcoholic liver disease. RESULTS: Severe liver disease initiates highly elevated B12 levels in plasma and a lowered liver tissue total B12 concentration. The percent of B12 distributed to holo TC II is significantly depleted during liver disease. In contrast, holo TC I and III are elevated in plasma during liver disease and contain more B12 than controls. Total B12 and B12 distributed to TC are lower in diseased liver tissue. CONCLUSION: Severe alcoholic liver disease involves leakage of total B12 from liver tissue into the plasma. Holo TC I and III concentration increases in plasma; this preserves the high plasma B12 from being excreted. However, plasma holo TC II B12 distribution is decreased, indicating that there is a depression of exogenous B12 entering the plasma and tissues. In severe liver disease, liver tissue B12 binding and storage by TC is disrupted and causes B12 to leak out of the liver into the circulation. Eventually liver disease could produce enough severe tissue B12 deficits to cause metabolic dysfunction despite elevated plasma total B12. Elevation of plasma B12, accompanied by a lowering of holo TC II distribution, seemed to be a useful index of liver disease severity suggesting preventive treatment.

Humans↗
PubMed1998

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) mortality in industrialized nations, 1987-1991.

OBJECTIVE: To compare patterns of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) mortality in 11 selected industrialized countries with highly developed death registration systems and a broad range of cumulative AIDS incidence rates. METHODS: Data on HIV/AIDS mortality were obtained from the World Health Organization (WHO) and Statistics Canada for the years 1987-1991. We obtained data for Australia, Canada, Denmark, France, the former Federal Republic of Germany, Italy, the Netherlands, New Zealand, Spain, Switzerland, and the US, stratified by sex and 5-year age groups. Population figures were obtained from national censal, post-censal or interpolated annual estimates compiled by WHO and from Statistics Canada. RESULTS: A total of 141534 deaths were attributed to HIV/AIDS (126224 in men and 15310 in women) in the 11 countries from 1987 to 1991. The majority of deaths (73.7%) occurred in the US. Other countries contributing substantially to the number of deaths were France (7.1%), Italy (4.9%), Spain (4.9%), former West Germany (3.5%), and Canada (3.0%). Age-specific death rates for men aged 25-44 years in 1991 were highest in the USA at 47.1 per 100000 population and highest for women in Switzerland at 7.7 per 100000 population. Potential years of life lost (PYLL) before age 75 years were highest for males in the US (2388 per 100000 population) and for females in Switzerland (373 per 100000 population). The lowest rates were in New Zealand (339 per 100000 population in men and 6.5 per 100000 population in women). CONCLUSIONS: This historical demographic analysis indicates that mortality resulting from HIV infection and AIDS among men and women varies considerable by country. Rates of death were highest in the US and lowest in Australia, the Netherlands, and New Zealand.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Endothelial cell effect on smooth muscle cell collagen synthesis.

UNLABELLED: Extracellular matrix (ECM) constitutes the bulk of mature intimal hyperplastic lesions. To determine if endothelial cells (ECs) inhibit smooth muscle cell (SMC) collagen synthesis, bovine aortic SMCs were cultured on plastic semipermeable membranes either alone or opposite ECs. SMCs were pulsed with 4 microCi/ml [3H]proline for 3 days and collagen synthesis was measured as trichloroacetic acid-precipitable counts in conditioned media and in cell lysate fractions. Each was standardized to SMC DNA (cpm/microgram DNA). EC effect on SMC gene expression of type I collagen was studied using Northern analysis. To determine whether TGF-beta 1 activation is involved in collagen synthesis regulation, parallel studies were performed in the presence of a neutralizing antibody to TGF-beta 1 (25 micrograms/ml) or aprotinin (a plasmin inhibitor, 200 micrograms/ml). SMCs cocultured with ECs were either untreated or treated with 5 ng/ml TGF-beta 1. The effect of culture substrate on EC-SMC interaction was studied by repeating experiments on type I collagen (CI), matrigel (MG), fibronectin (FN), and type IV collagen (CIV). RESULTS: Compared to SMCs cultured alone, ECs inhibited SMC collagen synthesis by 40 +/- 5% (P < 0.01) and gene expression of type I collagen by 60 +/- 4% (P < 0.01). The addition of neutralizing TGF-beta 1 Ab or aprotinin to SMCs cultured alone had no effect on collagen synthesis. Collagen synthesis in SMCs cultured alone on MG was reduced by 49% and by 16% on CIV when compared to SMCs cultured on plastic (plastic: 100 +/- 12% vs MG: 51 +/- 15% vs CIV: 84 +/- 18%, P = 0.10). Collagen synthesis was increased in SMCs cultured alone on FN (195 +/- 14% vs plastic: 100 +/- 12, P < 0.001) and CI (207 +/- 17 vs plastic: 100 +/- 12, P < 0.001). ECs decreased SMC collagen synthesis by 18 +/- 4% when cocultured on CI (P < 0.05) and by 22 +/- 2% when cocultured on MG (P < 0.05). FN prevented EC inhibition of SMC collagen synthesis. CONCLUSIONS: ECs inhibit SMC collagen synthesis and downregulate SMC type I collagen gene expression. TGF-beta 1 does not appear to be involved in this process. Culture substrate composition can affect SMC collagen synthesis and EC modulation of this process.

Animals↗
PubMed1997

Peripheral afferents with common function cluster in the median nerve and somatotopically innervate the human palm.

Concentric needle electrodes with a central core diameter of 20-30 microm were used to explore median nerve fascicles in man. Such electrodes can simultaneously monitor subtle electrophysiological and topographical features even within parts of a fascicle. Single-unit recordings from myelinated fibres were more easily obtained at some intrafascicular sites than others. Typically, groups of identified myelinated fibres in these regions, possibly corresponding to a cluster of Ranvier nodes, tended to be fibres responding to stimuli of the same modality. These afferents innervated the glabrous skin of the human hand and fingers in a somatotopic manner. In particular, the somatotopy even seemed to be present at the receptor level in the skin. This novel aspect of peripheral nerve organisation is probably of fundamental importance for the interplay between peripheral and central processes involved in somatosensation both under normal conditions and in disease. Some clinical implications of the findings are discussed.

Adult↗
PubMed1996

Antioxidant survey to assess antagonism to redox stress using a prokaryotic and an eukaryotic system.

Using a prokaryote (Escherichia coli) and a metazoa-resembling eukaryote (Ochromonas danica), we surveyed antioxidants which might overcome redox stress imposed by menadione sodium bisulphite (MD) and buthionine sulphoximine (BSO). BSO oxidant stress was evident only in O. danica; MD oxidant stress was evident in both organisms. Glutathione, its precursors, e.g. cysteine, homocysteine, and 2-oxo-4-thiazolidine carboxylic acid, and red blood cells, emerged as prime antioxidants for relieving BSO and MD oxidant stress. BSO and MD oxidant activity and antioxidant-annulling effect in O. danica were judged comparable to those found in animal cells whereas the results E. coli were not entirely equivalent. The O. danica system emerged as a practical, rapid, and useful system for pinpointing oxidant stressors and antioxidants, and shows promise for studies with mammalian systems.

Antioxidants↗
PubMed1996

Holotranscobalamins in B12 and non B12 requiring prokaryotes and eukaryotes.

Transcobalamins, vitamin B12 binding proteins, deliver B12 to cell surface receptors which then permit B12 to cross cell membranes for metabolic use. There is little documentation concerning B12 binding proteins in bacteria and protists. We found that prokaryotes and eukaryotes requiring B12, as well as those protists synthesizing B12, also produce several transcobalamins for functionally transporting B12 similar to humans.

Animals↗
PubMed1996

Human plasma patterns during 14 days ingestion of vitamin E, beta-carotene, ascorbic acid, and their various combinations.

OBJECTIVE: We wanted to learn about plasma patterns of ascorbic acid (AA), beta carotene (BC), and vitamin E (vit E) when each or their various combinations were fed to humans. Conceivably, the combined absorption of these antioxidants could synergize maximum plasma redox potential. METHODS: Vit E (800 mg/day), BC (30 mg/day), and AA (1000 mg/day) were fed individually or in various combinations with each other to 91 volunteers divided into different feeding groups for 14 days. Plasma vit E, carotenes, and AA patterns were analyzed by standardized methods; values were compared with each group's baseline value. RESULTS: AA feeding did not significantly increase already saturated plasma AA concentrations above baseline. Intake of BC did not influence vitamin A (vit A) levels. Feeding of only vit E or only BC, with or without AA addition, or a combination of BC and vit E significantly increased plasma vit E and carotene levels after 2 days. A statistically (ANOVA) significant increase in plasma vit E above baseline was noted when vit E was ingested combined with AA or BC; this increase in plasma vit E was not significant when AA, BC and vit E were taken in combination. CONCLUSION: Our results show that BC or AA ingestion in combination with vit E significantly increases circulating vit E above that seen when vit E is individually ingested. Vit E in combination with BC or AA seems a practical means or increasing the circulating antioxidant potential afforded by vit E. Reasons why such synergism does not exist when an AA, BC, vit E combination is ingested is not yet obvious.

Adult↗
PubMed1996

A guide to computer-generated prescriptions.

The use of computer systems to produce prescriptions offers many benefits at a reasonable cost. This article summarises the benefits and costs and the steps recommended for general practitioners who wish to start using a computer to generate their prescriptions.

Australia↗
PubMed1994

The end of fertility: age, fecundity and fecundability in women.

Onset of capacity for childbearing in women is dated biologically by menarche, although actual onset may be delayed. The end of childbearing is less understood but recent demographic and biological research on fertility at older ages in clarifying the end of fertility. The demographic view of declining fertility with age is based on age-specific fertility in natural fertility populations, artificial insemination and pregnancy rates by age and World Fertility Survey data. New data from the Demographic and Health Surveys on exposure to the risk of pregnancy shows that whereas older women biologically need longer exposure to pregnancy, exposure declines on behavioural grounds such as duration of marriage. Actual fecundity is obscured by factors of fecundability. Recent research on medically assisted conception is adding to the understanding of declining fecundity with age, especially the relative contributions of endometrial and ovarian ageing. This paper reviews the available information on declining fertility with age and discusses the implications of the extension of fertility through new medical technologies.

Adult↗
PubMed1994

Biocidal action of chlorhexidine is annulled by nicotinic acid.

An analytical system comprising a bacterium and a protozoan was used to pinpoint the metabolic lesion whereby chlorhexidine (CLX) produced cell death. Nicotinic acid but not nicotinamide annulled the biocidal action of CLX. The results suggest that CLX may not permit bioconversion of nicotinamide to nicotinic acid to annul the growth inhibition induced by CLX.

Animals↗
PubMed1994

Electrophysiological evidence of Ranvier node clustering in human sensory nerve fascicles.

Thin concentric needle electrodes were used to explore intact median nerve fascicles in human subjects. In particular, the presence of single units, probably recorded from nodes of Ranvier, was studied in different parts of a fascicle. Single-unit activity in myelinated fibers was rarely found at numerous sites. In many other intrafascicular areas, a substantial number of single units could be discriminated in the same or nearby recording sites with the same technique. To account for the neurophysiological results, stochastic models and statistical tests were developed to test various hypotheses concerning intrafascicular nerve fiber arrangements. The acquired data suggested both an intrafascicular modality grouping of nerve fibers and a simultaneous clustering of the Ranvier nodes of these fibers within very restricted areas of a fascicle. It was further concluded that the yield when searching for units in different types of nerve preparations may depend upon the ultrastructure of the explored nerve segments.

Adult↗
PubMed1994

Vitamin activities in human portal, hepatic and femoral blood after vitamin ingestion.

The dynamics of intestinal absorption, blood concentration and distribution of thiamin, biotin, nicotinate, riboflavin, pantothenate, various folates (folic acid, folinic acid, pteroyltriglutamate), vitamins A, E, C, B12, and B6 were monitored in 12 patients by multiple simultaneous sampling of blood obtained by combined catheterization of portal vein, hepatic vein, and femoral artery after vitamin ingestion. All water-soluble vitamins proved elevated after vitamin ingestion principally in portal blood within 10 minutes as compared with hepatic and femoral blood. Elevated vitamin levels in portal blood--compared to hepatic and femoral blood--remained high even after 120 min. indicating that absorption from the gut was still progressing. In contrast, ingestion of the fat-soluble vitamins A and E evoked no elevated vitamin activity in portal blood. Within 10 min. after vitamin ingestion, all folates were converted into reduced and methylated 5-methyltetrahydrofolate (5-CH3THF) on passage through the gut. At this time, portal blood elevation of 5-CH3THF persisted before its elevation in hepatic or femoral blood. Presumably, the elevation was not due to the flushing of stored 5-CH5THF from tissues but rather of folate conversion to 5-CH3THF upon gut passage. The significance of these findings is discussed.

Administration, Oral↗
PubMed1993

Absorption and excretion of L-carnitine during single or multiple dosings in humans.

Changes of short-chain (free) and long-chain (acyl) carnitine activity (CA) in plasma, whole blood, red blood cells (rbc) and urine were induced (a) by ingestion of L-carnitine as a single dose of 500 mg, or 2500 mg, or (b) by ingestion of a daily dose of 2500 mg for 10 days. A single 500-mg dose induced insignificant increases of CA in blood constituents. However elevated free CA was noted in urine. Single or daily high doses--e.g. 2500 mg of carnitine--significantly increased free and acyl-CA in plasma, whole blood and urine, but these increases were low. Variations in dosage or frequency of carnitine intake led to no changes in rbc CA; presumably CA in plasma diffused only slowly into rbc. The apparent low absorption of carnitine suggests that oral therapy may not effect rapid repletion of body stores of CA.

Adult↗