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M Lundin

Publications and source records attributed to M Lundin.

31 records · Page 2Linked to original sources
PubMed1997

Interexaminer reliability in physical examination of the neck.

BACKGROUND: There are numerous clinical tests used in the evaluation of patients with symptoms arising from the cervical spine. It is necessary to use clinical tests with high validity and reliability. Previous studies of reliability of clinical tests used in the evaluation of the cervical spine have come to various conclusions, most of which suggest low reliability. This might be explained by differences between examiners in performance and where the limit of normality is placed. OBJECTIVE: To evaluate the interexaminer reliability of clinical tests used in everyday clinical work, where the examiners base their evaluations on a comparison between left and right sides. STUDY DESIGN: A total of 50 volunteers were examined by two physiotherapists. The interexaminer reliability of clinical tests included in the physical examination of patients with symptoms from the cervical spine was evaluated. METHODS: Two physiotherapists independently examined volunteers. RESULTS: An acceptable reliability was found for two of 10 clinical tests. CONCLUSION: When it is possible to compare left and right sides, it is possible to show acceptable reliability for some clinical tests. Reliability studies most often find low reliability, perhaps because of bias; clinical tests are not standardized. In future studies, greater efforts should be taken to reduce bias.

Adolescent↗
PubMed1994

Importance of a flanking AT-rich region in target site recognition by the GC box-binding zinc finger protein MIG1.

MIG1 is a zinc finger protein that mediates glucose repression in the yeast Saccharomyces cerevisiae. MIG1 is related to the mammalian Krox/Egr, Wilms' tumor, and Sp1 finger proteins. It has two fingers and binds to a GCGGGG motif that resembles the GC boxes recognized by these mammalian proteins. We have performed a complete saturation mutagenesis of a natural MIG1 site in order to elucidate its binding specificity. We found that only three mutations within the GC box retain the ability to bind MIG1: G1 to C, C2 to T, and G5 to A. This result is consistent with current models for zinc finger-DNA binding, which assume that the sequence specificity is determined by base triplet recognition within the GC box. Surprisingly, we found that an AT-rich region 5' to the GC box also is important for MIG1 binding. This AT box is present in all natural MIG1 sites, and it is protected by MIG1 in DNase I footprints. However, the AT box differs from the GC box in that no single base within it is essential for binding. Instead, the AT-rich nature of this sequence seems to be crucial. The fact that AT-rich sequences are known to increase DNA flexibility prompted us to test whether MIG1 bends DNA. We found that binding of MIG1 is associated with bending within the AT box. We conclude that DNA binding by a simple zinc finger protein such as MIG1 can involve both recognition of the GC box and flanking sequence preferences that may reflect local DNA bendability.

Amino Acid Sequence↗
PubMed1993

Inorganic pyrophosphate gives a membrane potential in yeast mitochondria, as measured with the permeant cation tetraphenylphosphonium.

Evidence for a membrane potential (delta psi) generating capacity of inorganic pyrophosphate (PPi) with inorganic pyrophosphatase in mitochondria from the yeast Saccharomyces cerevisiae is presented. Addition of PPi increases the accumulation of the permeant cation tetraphenylphosphonium (TTP+) in mitochondria, as measured with a TPP(+)-selective electrode or using [3H]TPP+. This accumulation is strongly inhibited by the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) but not by oligomycin, whereas accumulation of TPP+ induced by ATP is strongly inhibited by both FCCP and oligomycin. The values of delta psi obtained upon addition of PPi were similar to those obtained when yeast mitochondria were energized by NADH or ATP. Energization of the wild type yeast mitochondria with ATP resulted in higher delta psi values than those achieved when PPi was hydrolyzed, whereas the effect of PPi was more pronounced in mitochondria from a pyrophosphatase (PPase) overproducing yeast strain. These results clearly indicate that PPi is significant as an energy donor and that the yeast mitochondrial PPase, the gene for which we have recently cloned and sequenced, may participate in energy transfer reactions.

Adenosine Triphosphate↗
PubMed1992

Computer modeling of two inorganic pyrophosphatases.

The yeast Saccharomyces cerevisiae has two inorganic pyrophosphatases that are structurally related. One, PPA1, is a cytoplasmic enzyme. The other, PPA2, is located in the mitochondria and appears to be energy-linked. The sequence similarity of PPA1 and PPA2 is about 66% and the identity is about 50%. All amino acids known to be important for catalysis are conserved, except one glutamate which is substituted by an aspartate in PPA2. The structures of PPA2 and the cytoplasmic PPase from Schizosaccharomyces pombe were modeled based on the three dimensional structure of PPA1. Two cysteines in PPA2 and one in the S. pombe enzyme are located at the catalytic cleft. Four residues form an unique insertion near the entrance of the catalytic cleft in the mitochondrial enzyme.

Amino Acid Sequence↗
PubMed1992

Characterization of a mitochondrial inorganic pyrophosphatase in Saccharomyces cerevisiae.

We have studied a mitochondrial inorganic pyrophosphatase (PPase) in the yeast Saccharomyces cerevisiae. The uncoupler FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone) and the ionophores valinomycin and nigericin stimulate the PPase activity of repeatedly washed yeast mitochondria 2-3-fold. We have previously cloned a yeast gene, PPA2, encoding the catalytic subunit of a mitochondrial PPase. Uncouplers stimulate the PPase activity several-fold in mitochondria from both cells that overexpress PPA2 from a high copy number plasmid and cells with normal expression. These results indicate that the PPA2 polypeptide functions as an energy linked and membrane associated PPase. The stimulation of mitochondrial PPase activity by FCCP, but not by valinomycin and nigericin, was greatly enhanced by the presence of DTT. The antibiotics Dio-9, equisetin and the F0F1-ATPase inhibitor oligomycin also increase mitochondrial PPase activity several fold. This stimulation is much higher, whereas basal PPase activity is lower, in isotonic than in hypotonic solution, which indicates that intact membranes are a prerequisite for maximal effects.

Adenosine Triphosphatases↗
PubMed1992

Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity.

The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h. After 8 h, vascular disruption occurred with hemorrhages. At 24-48 h after dosing, mesenchymal necrosis and, on some occasions, amputation of digits was observed. In the craniofacial region, well-defined superficial hemorrhage was seen in the frontal and nasal region at 8 h. Histologically, subectodermal hemorrhage caused by vascular disruption and microfocal mesenchymal necrosis was observed. At 48 h, some fetuses showed severe diffuse intracranial and superficial hemorrhage, resulting in massive tissue damage, also in the central nervous system (CNS). Maternal heart rate, blood pressure, PO2, and PCO2 were also measured in awake pregnant rabbits 6 h after the last dose on day 16 after daily administration with 150 mg/kg during gestational days 14-16. An attempt was also made to measure fetal heart rate in anesthetized rabbits. The maternal heart rate and blood pressure decreased with about 15% in phenytoin-treated animals, resulting in a decrease in PO2 (approximately 15%) and an increase in PCO2 (approximately 15%). A decrease in fetal heart rate was also registered. The results thus indicate that phenytoin exerts its teratogenic effects by inducing fetal hypoxia, leading to vascular disrupture and necrosis of existing and developing structures.

Abnormalities, Drug-Induced↗
PubMed1991

Protein phosphorylation by inorganic pyrophosphate in yeast mitochondria.

Inorganic pyrophosphate can function as phosphate donor in protein phosphorylation reactions in yeast mitochondria. It was shown that, when PPi substitutes for ATP as inhibitor of the pyruvate dehydrogenase reaction, maximal activity is reached after a lag-period of 30-60 minutes. 32P-labeling of peptides shows that [32P]PPi gives about 25% of the labeling obtained by [gamma-32P]ATP in the protein kinase reaction. The PPi dependent phosphorylation is increased several fold by the presence of cold ATP.

Adenosine Triphosphate↗
PubMed1991

Yeast PPA2 gene encodes a mitochondrial inorganic pyrophosphatase that is essential for mitochondrial function.

We have cloned a gene encoding a mitochondrial inorganic pyrophosphatase (PPase) in the yeast Saccharomyces cerevisiae by low stringency hybridization to PPA1, the yeast gene for cytoplasmic PPase. The new gene, PPA2, is located on chromosome 13 and encodes a protein whose sequence is 49% identical to the cytoplasmic enzyme. The protein differs from cytoplasmic PPase in that it has a leader sequence enriched in basic and hydroxylated residues, which is typically found in mitochondrial proteins. Yeast cells overproducing PPA2 had a 47-fold increase in mitochondrial PPase activity. This activity was further stimulated 3-fold by the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which suggests that PPA2 is part of an energy-linked enzyme. Using gene disruptions, we found that PPA1 is required for cell growth. In contrast, cells disrupted for PPA2 are viable, but unable to grow on respiratory carbon sources. Fluorescence microscopy revealed that these cells have lost their mitochondrial DNA. We conclude that the mitochondrial PPase encoded by PPA2 is essential for mitochondrial function and maintenance of the mitochondrial genome.

Amino Acid Sequence↗
PubMed1987

Energy-dependent formation of free ATP in yeast submitochondrial particles, and its stimulation by oligomycin.

Yeast submitochondrial particles, in a Pi- and NADH-dependent reaction, produced low concentrations of free ATP in the absence of added ADP. This formation of free ATP, as measured by the luciferin-luciferase method, was strongly stimulated by oligomycin. For maximal stimulation, oligomycin was to be added not earlier than 5-10 min after the addition of NADH. Upon addition of antimycin or FCCP the system was completely inhibited. The amount of free ATP formed corresponded to one-third of the amount of bound ATP in submitochondrial particles. The stimulatory effect of oligomycin disappeared if the submitochondrial particles were spun down after oligomycin stimulation and then resuspended in the reaction medium, whereas submitochondrial particles with no oligomycin added initially were stimulated by oligomycin after the same procedure. A different picture emerged with addition of ADP. If the submitochondrial particles were preenergized with NADH in the presence of oligomycin before the addition of ADP the formation of free ATP upon subsequent addition of ADP was inhibited by oligomycin. In the presence of oligomycin, but lacking preenergization with NADH, a stimulation of free ATP formation was achieved with added ADP. A possible explanation for the stimulating effect of oligomycin on ATP formation in the absence of added ADP is that it enhances the release of bound ATP in an energy-requiring process. The release of only about one-third of the bound ATP could indicate that one of three nucleotide-binding subunits involved in the mechanism of ATP formation by ATP synthase is in a state suitable for such an energy-dependent release of ATP.

Adenosine Triphosphate↗
PubMedDate not supplied

A comparison of serum and tissue hCG beta as prognostic markers in colorectal cancer.

BACKGROUND: Production of the glycoprotein hormone hCG beta has been associated with aggressive behavior in nontrophoblastic tumors. In this study the prognostic value of serum level and tissue expression of hCG beta were compared in 232 patients with colorectal cancer. MATERIALS AND METHODS: Serum levels were measured with a hCG beta specific immunofluorometric assay. Tissue specimens were stained with the same monoclonal antibody as in the serum assay. RESULTS: The proportion of patients with a positive immunohistochemical expression of hCG beta was higher (22%) than the proportion with elevated serum levels (17%). The correlation between serum and tissue expression was moderate (kappa 0.298). Both serum and tissue expression of hCG beta were independent prognostic factors. hCG beta serum level was a stronger prognostic factor than tissue expression both in uni- and in multivariate analysis. The accuracy when predicting 5-year survival status of the patients was highest (63%) when using the combined results of serum and tissue expression. CONCLUSIONS: There is a moderate correlation between hCG beta expression in serum and in tissue. The predictive accuracy of serum hCG beta was higher than the predictive accuracy of tissue expression, and the prognostic accuracy was further slightly increased when using a combination of tissue and serum expression.

Adult↗