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Biomedical subjects

K Larsen

Publications and source records attributed to K Larsen.

At least 19 recordsLinked to original sources
PubMed1995

The effect of a stroke unit: reductions in mortality, discharge rate to nursing home, length of hospital stay, and cost. A community-based study.

BACKGROUND AND PURPOSE: Treatment of stroke patients in specialized stroke units has become more frequent, yet the effect of this treatment has not been determined. METHODS: In a community-based, prospective, and consecutive study of 1241 unselected acute stroke patients, we compared outcome of stroke treatment between two neighboring communities within Greater Copenhagen: the Bispebjerg community, where all acute stroke patients are treated and rehabilitated on a stroke unit, and Frederiksberg community, where all acute stroke patients are treated and rehabilitated on general neurological and medical wards. Except for the different organization of stroke treatment, the two communities and the two patient groups were comparable. Specifically, age, sex, marital status, prestroke residence, and stroke severity were not statistically different between patients treated on the stroke unit and those treated on the general neurological and medical wards. Multivariate regression analyses were used to estimate the independent influence of stroke unit treatment on outcome. RESULTS: Stroke unit treatment significantly reduced in-hospital mortality (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.34 to 0.74; P < .001), case-fatality rate (OR, 0.45; CI, 0.28 to 0.71; P < .001), 6-month mortality (OR, 0.57; CI, 0.39 to 0.82; P = .002), 1-year mortality (OR, 0.59; CI, 0.42 to 0.84; P = .003), and discharge rate to a nursing home (OR, 0.61; CI, 0.38 to 0.98; P = .04). Discharge rate to the patient's own home was significantly increased (OR, 1.90; CI, 1.30 to 2.70; P < .001). The length of hospital stay (including rehabilitation) was reduced significantly by 30% in patients treated on the stroke unit despite their lower mortality (P < .001). The savings due to stroke unit treatment were estimated at 1313 bed-days and three places at a nursing home per 100 stroke patients. CONCLUSIONS: Treatment of unselected acute stroke patients on a stroke care unit saved lives, reduced the length of hospital stay, reduced the frequency of discharge to a nursing home, and potentially reduced cost.

Aged↗
PubMed1995

Genetic anticipation in Parkinson's disease.

We studied age at onset and family history of 137 patients (probands) with the diagnosis of idiopathic Parkinson's disease (PD). Probands (N = 21) who had an affected parent, aunt, or uncle were younger (p = 0.0001) at the onset of PD (47.7 +/- 8.8 years) than were probands (N = 11) who had an affected sib only (60.3 +/- 12.9 years) and probands (N = 105) who had no affected sib, parent, aunt, or uncle (59.2 +/- 11.4 years). Age at onset of affected family members differed significantly between generations (p = 0.0001). Age at onset was earlier, by an average of 17 years, in the proband generation than in the parental generation. The intrafamily variation in the calendar year of onset was too great to suggest a common point of exposure. Our data are most compatible with genetic anticipation, which could suggest involvement of an unstable trinucleotide repeat.

Age Factors↗
PubMed1994

[Congenital fructose intolerance. New molecular aspects].

Hereditary fructose intolerance is a human autosomal recessive disease caused by a deficiency of aldolase B that results in an inability to metabolize fructose and related sugars. Molecular analyses have shown that most defects are caused by point mutations in critical regions of the aldolase B gene. We have performed PCR-based DNA analysis of members of two Norwegian families with hereditary fructose intolerance. The affected individuals from both families contained a point mutation (A149P) in exon 5 of the aldolase B gene. Molecular diagnosis of fructose intolerance is rapid and specific, and causes no inconvenience to the patient. It should be preferred to conventional fructose intolerance tests and visceral biopsy analyses.

Adult↗
PubMed1994

Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.

Crystal structures of seryl-tRNA synthetase from Thermus thermophilus complexed with two different analogs of seryl adenylate have been determined at 2.5 A resolution. The first complex is between the enzyme and seryl-hydroxamate-AMP (adenosine monophosphate), produced enzymatically in the crystal from adenosine triphosphate (ATP) and serine hydroxamate, and the second is with a synthetic analog of seryl adenylate (5'-O-[N-(L-seryl)-sulfamoyl]adenosine), which is a strong inhibitor of the enzyme. Both molecules are bound in a similar fashion by a network of hydrogen bond interactions in a deep hydrophilic cleft formed by the antiparallel beta sheet and surrounding loops of the synthetase catalytic domain. Four regions in the primary sequence are involved in the interactions, including the motif 2 and 3 regions of class 2 synthetases. Apart from the specific recognition of the serine side chain, the interactions are likely to be similar in all class 2 synthetases.

Adenosine↗
PubMed1994

Increased risk of Parkinson's disease in parents and siblings of patients.

We studied the incidence of Parkinson's disease in 586 first-degree relatives (parents and siblings) of 114 randomly ascertained white patients with idiopathic Parkinson's disease and in 522 first-degree relatives of 114 age-matched unrelated white control subjects. Sixteen percent of patients had a family history as compared to 4% of control subjects (p < 0.01). The age-specific cumulative incidence was higher in the first-degree relatives of patients than in the first-degree relatives of control subjects (p = 0.007). The age-adjusted odds ratio was 3.5 (95% confidence interval: 1.3-9.4; p = 0.014). These results suggest that genes contribute to the etiology of Parkinson's disease.

Aged↗
PubMed1994

A small percentage of influenza virus M1 protein contains zinc but zinc does not influence in vitro M1-RNA interaction.

A peptide containing the CCHH motif, the putative zinc-binding sequence of influenza virus M1 protein, was found to bind zinc in a one-to-one complex with the characteristics of a typical zinc-binding peptide. Intact influenza virus also contained zinc and we show that this zinc is bound to the M1 protein in the virus. However, only a small proportion of M1 contained zinc: 4% in virus and 6 to 9% in isolated protein. One strain, B/Yamagata/16/88, consistently contained more zinc: 15 to 20% both in virus and in isolated protein. We also determined the RNA binding and transcription inhibition activities of various M1 proteins and found that the zinc content of M1 had no influence on either activity. We suggest that the zinc in M1 has a structural role in the virion other than nucleic acid binding.

Amino Acid Sequence↗
PubMed1994

A protein binding AT-rich sequence in the soybean leghemoglobin c3 promoter is a general cis element that requires proximal DNA elements to stimulate transcription.

A nodule nuclear factor, NAT2, interacts with two AT-rich binding sites (NAT2 BS1 and NAT2 BS2) in the soybean leghemoglobin (lb) c3 promoter. In transgenic Lotus corniculatus nodules, an oligonucleotide containing NAT2 BS1 activated an inactive -159 lbc3 promoter when placed immediately upstream of the promoter. The activation was independent of the orientation of NAT2 BS1 but was dependent on its position in the promoter. The abilities of different mutated binding sites to activate expression in vivo were correlated to their respective in vitro affinities for binding NAT2. This suggested that the interaction between NAT2 and NAT2 BS1 is responsible for the observed reactivation. Further activation experiments with the lbc3 and the leaf-specific Nicotiana plumbaginifolia ribulose bisphosphate carboxylase/oxygenase small subunit (rbcS-8B) promoter suggested that another specific cis element(s) is required for the function of NAT2 BS1. Thus, the -102 lbc3 promoter lacking the organ-specific element (-139 to -102) was not reactivated by the presence of the binding site, and the rbcS-8B promoter required sequences between -312 and -257 to be activated by NAT2 BS1. This implies that NAT2 has to work in combination with other trans-acting factor(s) to increase expression. The finding of NAT2-like binding activities in different plant organs and the specific expression of the hybrid NAT2 BS1/-312 rbcS-8B promoter in leaves suggest that NAT2 is a general activator of transcription.

Arylamine N-Acetyltransferase↗
PubMed1994

Clinical course of patients with primary nasal polyps.

A follow-up study on 180 patients treated for the first time for nasal polyps was performed. The follow-up period was from 1 to 8 years with a median of 57 months. The majority of patients had postoperative topical steroid treatment. 65.6% of patients had one polypectomy, 17.8% had two polypectomies, 10% had 3, 2.8% had 4, and 3.9% of patients had 5-10 polypectomies performed during the follow-up period. Patients without asthma, acute recurrent or chronic sinusitis, acetylsalicylic acid intolerance, or allergy had fewer polypectomies and less topical steroid treatment than patients with these characteristics. The recurrence profile between the first and second polypectomy described with the life-table method showed a slow decline in the number of patients with only one polypectomy. The time span needed before significant clinical symptoms occurred after the first polypectomy indicates that not all primary polyp patients are prone to recurrence. Nasal polyps is probably a manifestation of different clinical and aetio-pathogenetic entities. Further identification of such entities is needed to improve treatment strategy.

Adolescent↗
PubMed1993

Non-reflex and reflex mediated ankle joint stiffness in multiple sclerosis patients with spasticity.

In this study, we have measured the passive, the intrinsic, and the reflex-mediated mechanical response to stretch of the ankle extensors and flexors in 13 spastic multiple sclerosis patients and 10 healthy control subjects. In the ankle flexors, the patients had no reflex-mediated stiffness. The passive stiffness was increased by 138% (95% confidence interval: 26-91%) and the intrinsic stiffness by 79% (41-158%) when compared with the healthy subjects. In the ankle extensors, the reflex-mediated stiffness and the intrinsic stiffness of the patients were equal to the reflex-mediated and the intrinsic stiffness in healthy subjects. The passive stiffness was increased by 152% (41-352%). We conclude that spastic muscles in multiple sclerosis patients have an increased non-reflex stiffness (passive plus intrinsic stiffness), and that the reflex-mediated stiffness in the extensors during a sustained voluntary contraction does not differ significantly from healthy subjects.

Adult↗
PubMed1993

Differential expression within the glutamine synthetase gene family of the model legume Medicago truncatula.

The glutamine synthetase (GS) gene family of Medicago truncatula Gaertn. contains three genes related to cytosolic GS (MtGSa, MtGSb, and MtGSc), although one of these (MtGSc) appears not to be expressed. Sequence analysis suggests that the genes are more highly conserved interspecifically rather than intraspecifically: MtGSa and MtGSb are more similar to their homologs in Medicago sativa and Pisum sativum than to each other. Studies in which gene-specific probes are used show that both MtGSa and MtGSb are induced during symbiotic root nodule development, although not coordinately. MtGSa is the most highly expressed GS gene in nodules but is also expressed to lower extents in a variety of other organs. MtGSb shows higher levels of expression in roots and the photosynthetic cotyledons of seedlings than in nodules or other organs. In roots, both genes are expressed in the absence of an exogenous nitrogen source. However the addition of nitrate leads to a short-term, 2- to 3-fold increase in the abundance of both mRNAs, and the addition of ammonium leads to a 2-fold increase in MtGSb mRNA. The nitrogen supply, therefore, influences the expression of the two genes in roots, but it is clearly not the major effector of their expression. In the discussion section, the expression of the GS gene family of the model legume M. truncatula is compared to those of other leguminous plants.

Ammonia↗
PubMed1992

Recognition of substrates by tyrosylprotein sulfotransferase. Determination of affinity by acidic amino acids near the target sites.

The sulfation of proteins by tyrosylprotein sulfotransferase (TPST) is highly site-specific. In this study, we examined the sequence specificity of the target site for TPST by determining the kinetics of rat liver TPST with peptides related to the sequence of the C4 component of complement. The data obtained from this study demonstrate that selective elimination of negative charges from the -5 to +5 region of the acceptor tyrosine, either by removal or by isosteric substitution or the acidic amino acids in the region, produced a substantial change in the Km value, with relatively little effect on Vmax. Substitutions at -1 and +1 positions increase the Km value by 22- and 4-fold, respectively, whereas removal of the acidic amino acids from the -5, -4, or +4 positions increased the Km values by a factor of 2-4. The effect of elimination of an acidic amino acid on the Km value was constant and specific for its particular position in relation to tyrosine, and the effect of modification of more than one amino acid was multiplicative. This study provides evidence that: 1) acidic residues near tyrosines promote sulfation by increasing the affinity of enzyme-substrate binding and have little effect on catalytic rate; 2) the contribution of each acidic residue to affinity for TPST is independent and varies according to position relative to the acceptor tyrosine; and 3) the enzyme interacts with a segment of at least 4-5 residues on each side of the tyrosine, with the residues on the -1 and +1 positions being the most important determinants. In general, residues on the NH2-terminal side of the tyrosine have a greater effect on affinity for TPST.

Amino Acid Sequence↗
PubMed1992

Marked increase of stroke incidence in men between 1972 and 1990 in Frederiksberg, Denmark.

BACKGROUND AND PURPOSE: Stroke incidence declined until the end of the 1970s in the United States, and the decline continued into the 1980s in Japan. The purpose of this study was to determine possible temporal changes of stroke incidence in a European community. METHODS: A prospective stroke registry was established in the community of Frederiksberg (population, approximately 90,000), Denmark, in the two periods 1972-1974 and 1989-1990. All patients suspected of stroke were clinically evaluated by a neurologist. Only patients with first-ever stroke were included. Complete case ascertainment was ensured by registration of both hospitalized and nonhospitalized patients. Death certificates were also scrutinized. RESULTS: A total of 927 patients with first-ever stroke was recorded. The annual stroke incidence rate per 1,000 increased by 18% from 2.6 in 1972-1974 to 3.1 in 1989-1990 (p < 0.01). This increase was due solely to a 42% increase in men, in whom stroke incidence rose from 2.1 to 3.0 (p < 0.0005). Incidence was unchanged in women at 3.0 and 3.1, respectively. The incidence rates from 1972-1974 were age and sex adjusted to the 1990 population. After adjustment to the Danish population, stroke incidence in Denmark was 2.0 for all, 2.3 for men, and 1.9 for women. In the second study period computed tomography or necropsy was performed in 85% of cases; 2.4/1,000 had cerebral infarction; 0.20/1,000 had intracerebral hemorrhage; and 0.02/1,000 had subarachnoid hemorrhage. CONCLUSIONS: In a period when decline in stroke incidence has stopped in the United States and has continued in Japan, a marked increase of stroke incidence in Danish men was observed.

Aged↗
PubMed1992

Psoriasis treatment with vitamin D derivatives.

The naturally occurring 1,25(OH)2 vitamin D3 and the two synthetic derivatives 1,24(OH)2 vitamin D3 and calcipotriol (Calcipotriol, INN, Calcipotriene, USAN) have a profound effect on keratinocyte proliferation and differentiation. Clinical trials have shown an effect of all three derivatives in psoriasis. The limiting factor for the use of 1,25(OH)2 vitamin D3 is the risk of hypercalcemia, which is 100 to 200 times less for calcipotriol and that may be less also for 1,24(OH)2 vitamin D3. Presently, calcipotriol in an ointment base has been marketed in a number of countries and represents an alternative to treatment with topical glucocorticoids and dithranol.

Calcitriol↗