Biomedical subjects

A J Koning

Publications and source records attributed to A J Koning.

10 recordsLinked to original sources

PubMed2006

Partial photoneutron cross sections for the isomeric state 180Tam.

Photoneutron cross sections for (181)Ta(y, n) (180)Ta(m) were determined from simultaneous measurements of total cross sections (sigma(tot) and ground-state cross sections (sigma(gs)) for (180)Ta in photodisintegration of with laser Compton-backscattered rays. Techniques of direct neutron counting and photoactivation were used for the measurement of sigma(tot) and sigma(gs), respectively. The partial cross sections for the isomeric state serves as a novel probe of the nuclear level density of (180)Ta. Implications for the p- and s-process nucleosynthesis of (180)Ta(m) are given.

Journal Article↗

PubMed1999

The role of the 3-hydroxy 3-methylglutaryl coenzyme A reductase cytosolic domain in karmellae biogenesis.

In all cells examined, specific endoplasmic reticulum (ER) membrane arrays are induced in response to increased levels of the ER membrane protein 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase. In yeast, expression of Hmg1p, one of two yeast HMG-CoA reductase isozymes, induces assembly of nuclear-associated ER stacks called karmellae. Understanding the features of HMG-CoA reductase that signal karmellae biogenesis would provide useful insights into the regulation of membrane biogenesis. The HMG-CoA reductase protein consists of two domains, a multitopic membrane domain and a cytosolic catalytic domain. Previous studies had indicated that the HMG-CoA reductase membrane domain was exclusively responsible for generation of ER membrane proliferations. Surprisingly, we discovered that this conclusion was incorrect: sequences at the carboxyl terminus of HMG-CoA reductase can profoundly affect karmellae biogenesis. Specifically, truncations of Hmg1p that removed or shortened the carboxyl terminus were unable to induce karmellae assembly. This result indicated that the membrane domain of Hmg1p was not sufficient to signal for karmellae assembly. Using beta-galactosidase fusions, we demonstrated that the carboxyl terminus was unlikely to simply serve as an oligomerization domain. Our working hypothesis is that a truncated or misfolded cytosolic domain prevents proper signaling for karmellae by interfering with the required tertiary structure of the membrane domain.

Carbocyanines↗

PubMed1996

Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations.

In all eucaryotic cell types analyzed, proliferations of the endoplasmic reticulum (ER) can be induced by increasing the levels of certain integral ER proteins. One of the best characterized of these proteins is HMG-CoA reductase, which catalyzes the rate-limiting step in sterol biosynthesis. We have investigated the subcellular distributions of the two HMG-CoA reductase isozymes in Saccharomyces cerevisiae and the types of ER proliferations that arise in response to elevated levels of each isozyme. At endogenous expression levels, Hmg1p and Hmg2p were both primarily localized in the nuclear envelope. However, at increased levels, the isozymes displayed distinct subcellular localization patterns in which each isozyme was predominantly localized in a different region of the ER. Specifically, increased levels of Hmg1p were concentrated in the nuclear envelope, whereas increased levels of Hmg2p were concentrated in the peripheral ER. In addition, an Hmg2p chimeric protein containing a 77-amino acid lumenal segment from Hmg1p was localized in a pattern that resembled that of Hmg1p when expressed at increased levels. Reflecting their different subcellular distributions, elevated levels of Hmg1p and Hmg2p induced sets of ER membrane proliferations with distinct morphologies. The ER membrane protein, Sec61p, was localized in the membranes induced by both Hmg1p and Hmg2p green fluorescent protein (GFP) fusions. In contrast, the lumenal ER protein, Kar2p, was present in Hmg1p:GFP membranes, but only rarely in Hmg2p:GFP membranes. These results indicated that the membranes synthesized in response to Hmg1p and Hmg2p were derived from the ER, but that the membranes were not identical in protein composition. We determined that the different types of ER proliferations were not simply due to quantitative differences in protein amounts or to the different half-lives of the two isozymes. It is possible that the specific distributions of the two yeast HMG-CoA reductase isozymes and their corresponding membrane proliferations may reveal regions of the ER that are specialized for certain branches of the sterol biosynthetic pathway.

Endoplasmic Reticulum↗

PubMed1993

DiOC6 staining reveals organelle structure and dynamics in living yeast cells.

When present at low concentrations, the fluorescent lipophilic dye, DiOC6, stains mitochondria in living yeast cells [Pringle et al.: Methods in Cell Biol. 31:357-435, 1989; Weisman et al.: Proc. Natl. Acad. Sci. U.S.A. 87:1076-1080, 1990]. However, we found that the nuclear envelope and endoplasmic reticulum were specifically stained if the dye concentration was increased or if certain respiratory-deficient yeast strains were examined. The quality of nuclear envelope staining with DiOC6 was sufficiently sensitive to reveal alterations in the nuclear envelope known as karmellae. These membranes were previously apparent only by electron microscopy. At the high dye concentrations required to stain the nuclear envelope, wild-type cells could no longer grow on non-fermentable carbon sources. In spite of this effect on mitochondrial function, the presence of high dye concentration did not adversely affect cell viability or general growth characteristics when strains were grown under standard conditions on glucose. Consequently, time-lapse confocal microscopy was used to examine organelle dynamics in living yeast cells stained with DiOC6. These in vivo observations correlated very well with previous electron microscopic studies, including analyses of mitochondria, karmellae, and mitosis. For example, cycles of mitochondrial fusion and division, as well as the changes in nuclear shape and position that occur during mitosis, were readily imaged in time-lapse studies of living DiOC6-stained cells. This technique also revealed new aspects of nuclear disposition and interactions with other organelles. For example, the nucleus and vacuole appeared to form a structurally coupled unit that could undergo coordinated movements. Furthermore, unlike the general view that nuclear movements occur only in association with division, the nucleus/vacuole underwent dramatic migrations around the cell periphery as cells exited from stationary phase. In addition to the large migrations or rotations of the nucleus/vacuole, DiOC6 staining also revealed more subtle dynamics, including the forces of the spindle on the nuclear envelope during mitosis. This technique should have broad application in analyses of yeast cell structure and function.

Carbocyanines↗

PubMed1992

Developmental expression of tomato heat-shock cognate protein 80.

Heat-shock protein 80 (HSP80) is a major heat-shock protein induced in yeast and animals both by heat shock and by specific developmental events. In plants, a heat-shock-induced HSP80 cDNA has been described, although no information concerning developmental regulation of HSP80 genes is available. We have characterized a tomato (Lycopersicon esculentum) gene encoding a typical HSP80 protein. This gene, called HSC80, is interrupted by two introns, 995 and 109 bp long. Northern blot analyses and in situ RNA hybridization show that HSC80 mRNA is abundant in shoot and root apices and in fertilized ovaries up to 6 d postanthesis but is rare in mature leaves. Heat shock increased mRNA levels in mature leaves but only 3-fold. Developmental regulation of the HSC80 gene was confirmed by fusing 2 kb of its 5' region to the beta-glucuronidase reporter gene and introducing the chimeric gene into tomatoes. The roots of transformants showed high beta-glucuronidase expression in the apex and in lateral root primordia but not in mature tissue. Expression in the shoot was up to 10-fold higher in the apex than in mature leaves. Thus, HSC80 is preferentially expressed in shoot and root apices during normal development.

Journal Article↗

PubMed1991

Cell-specific expression of plant histone H2A genes.

Histone H2A is a component of eukaryotic chromatin whose expression has not been studied in plants. We isolated and characterized a tomato and a pea cDNA encoding histone H2A. We found that in tomato H2A is encoded by a small gene family and that both the pea and the tomato mRNAs are polyadenylated. Tomato H2A has 82% amino acid residue identity to pea H2A, 83% to wheat, and 65% to human and yeast H2A. Plant H2As differ from fungal and animal H2As in their amino-terminal and carboxy-terminal regions. Carboxy-terminal plant H2A regions contain the motif SPKK, a peptide implicated in binding of A/T-rich DNA regions. By using RNA gel blot analysis, we determined that the steady-state mRNA level of these genes was abundant in apices and early developing fruit and very low in mature tissues. In situ RNA hybridization showed strong spatial regulation because the mRNA was abundant in some cells and not detectable in others. In tomato shoot tips, H2A-expressing cells were distributed irregularly in or near meristems. In tomato or pea root tips, expressing cells were concentrated near the apex, and their distribution was consistent with that expected of cycling cells. Other H2A transcripts were found in nondividing cortical cells that are known to undergo endoduplication during the late maturation phase of primary development.

Amino Acid Sequence↗

PubMed1990

Regularity in alcohol distributions: implications for the collective nature of drinking behaviour.

The assumption of a one parameter lognormal distribution in the Ledermann theory is relaxed. Implications of only regularity in distributional form for the collective nature of drinking behaviour are considered. It is shown that there must be a so-called point of attraction over which an increase in mean consumption will result in a decrease of percentile point value. The validity of regularity in distributional form and the practical relevance of the Ledermann model is discussed. An example from Dutch data on alcohol consumption among men obtained in 1970 and 1985 illustrates the relevance of an existing point of attraction.

Alcohol Drinking↗

PubMed1988

Renal function following open heart surgery: the influence of postoperative artificial ventilation.

In order to detect changes in renal perfusion and function in the postoperative period of open heart surgery, a prospective study of 21 patients following open heart surgery was performed. Cardiac output, renal blood flow, glomerular filtration and renal function parameters were determined during intermittent positive pressure ventilation (IPPV), and during spontaneous ventilation (SV). During IPPV, renal perfusion was found to be substantially decreased. The glomerular filtration rate was also reduced, but to a lesser extent, implying that the changes were due to a selective increase in postglomerular vascular resistance. The clearances of urea and creatinine were decreased during IPPV, but the clearances of osmoles and potassium were higher. The reabsorption of sodium, potassium and osmoles were also decreased during IPPV, but not that of urea. These findings are consistent with the development of increased renal venous pressure during IPPV, caused by impeded venous return to the heart. In the low cardiac output range a cardiac index in excess of 0.5l/min/m2 during IPPV seems necessary to achieve the same renal perfusion as during SV.

Acute Kidney Injury↗

PubMed1987

Optimal perfusion during extra-corporeal circulation.

A multivariate analysis of 130 consecutive patients operated during one month in our hospital was carried out to determine the influence of age and blood flow during cardiopulmonary bypass on the renal response to cardiac surgery. The postoperative level of serum creatinine could be related to three variables: preoperative serum creatinine, age and lowest blood flow during cardiopulmonary bypass. A higher blood flow is needed during cardiopulmonary bypass in older patients and in patients with a raised pre-operative serum creatinine to prevent deterioration in renal function postoperatively. A nomogram is given for the lowest blood flow during CPB, corrected for age and the pre-operative serum creatinine level, which will result in a desired postoperative serum creatinine of 110 mumol/l.

Adult↗

PubMed1985

Serious acute renal failure following open heart surgery.

The influence of 51 preoperative, peroperative and postoperative variables on the development of serious acute renal failure (ARF) following open heart surgery was studied. Although a large number of significant variables was found, a logit-model with only 2 explanatory variables showed an almost perfect fit. With this model the chances of serious ARF up to 90% were estimated. The results suggest that a critical circulation is the main cause of serious ARF. Furthermore, a reduced ability to cope with a critical circulation without renal failure plays an important role in the pathogenesis. There is a higher risk of serious ARF for patients older than 70, especially when circulatory support with dopamine is needed.

Acute Kidney Injury↗