PubMed Health⌕ Search

Biomedical subjects

M Hauge

Publications and source records attributed to M Hauge.

At least 19 recordsLinked to original sources

Mutational effects on conformational changes of the dephospho- and phospho-forms of the Na+,K+-ATPase.

Gly263 of the rat kidney Na(+),K(+)-ATPase is highly conserved within the family of P-type ATPases. Mutants in which Gly263 or the juxtaposed Arg264 had been replaced by alanine were expressed at high levels in COS-1 cells and characterized functionally. Titrations of Na(+),K(+), ATP, and vanadate dependencies of Na(+),K(+)-ATPase activity showed changes in the apparent affinities relative to wild-type compatible with a displacement of the E(1)-E(2) conformational equilibrium in favor of E(1). The level of the K(+)-occluded form was reduced in the Gly263-->Ala and Arg264-->Ala mutants, and the rate constant characterizing deocclusion of K(+) or Rb(+) was increased as much as 20-fold in the Gly263-->Ala mutant. Studies of the sensitivity of the phosphoenzyme to K(+) and ADP showed a displacement of the E(1)P-E(2)P equilibrium of the phosphoenzyme in favor of E(1)P, and dephosphorylation experiments carried out at 25 degrees C on a millisecond time scale using a quenched-flow technique demonstrated a reduction of the E(1)P to E(2)P conversion rate in the mutants. Hence, the mutations displaced the conformational equilibria of dephosphoenzyme and phosphoenzyme in parallel in favor of the E(1) and E(1)P forms. The observed effects were more pronounced in the Gly263-->Ala mutant compared with the Arg264-->Ala mutant. Leu332 mutations that likewise displaced the conformational equilibria in favor of E(1) and E(1)P were also studied. Unlike the Gly263-->Ala mutant the Leu332 mutants displayed a wild-type like rate of K(+) deocclusion. Thus, the effect of the Gly263 mutation on the E(1)-E(2) conformational equilibrium seems to be caused mainly by an acceleration of the K(+)-deoccluding step, whereas in the Leu332 mutants the rate of the reverse reaction seems to be reduced.

Adenosine Triphosphate↗

A comprehensive genetic study of streptococcal immunoglobulin A1 proteases: evidence for recombination within and between species.

An analysis of 13 immunoglobulin A1 (IgA1) protease genes (iga) of strains of Streptococcus pneumoniae, Streptococcus oralis, Streptococcus mitis, and Streptococcus sanguis was carried out to obtain information on the structure, polymorphism, and phylogeny of this specific protease, which enables bacteria to evade functions of the predominant Ig isotype on mucosal surfaces. The analysis included cloning and sequencing of iga genes from S. oralis and S. mitis biovar 1, sequencing of an additional seven iga genes from S. sanguis biovars 1 through 4, and restriction fragment length polymorphism (RFLP) analyses of iga genes of another 10 strains of S. mitis biovar 1 and 6 strains of S. oralis. All 13 genes sequenced had the potential of encoding proteins with molecular masses of approximately 200 kDa containing the sequence motif HEMTH and an E residue 20 amino acids downstream, which are characteristic of Zn metalloproteinases. In addition, all had a typical gram-positive cell wall anchor motif, LPNTG, which, in contrast to such motifs in other known streptococcal and staphylococcal proteins, was located in their N-terminal parts. Repeat structures showing variation in number and sequence were present in all strains and may be of relevance to the immunogenicities of the enzymes. Protease activities in cultures of the streptococcal strains were associated with species of different molecular masses ranging from 130 to 200 kDa, suggesting posttranslational processing possibly as a result of autoproteolysis at post-proline peptide bonds in the N-terminal parts of the molecules. Comparison of deduced amino acid sequences revealed a 94% similarity between S. oralis and S. mitis IgA1 proteases and a 75 to 79% similarity between IgA1 proteases of these species and those of S. pneumoniae and S. sanguis, respectively. Combined with the results of RFLP analyses using different iga gene fragments as probes, the results of nucleotide sequence comparisons provide evidence of horizontal transfer of iga gene sequences among individual strains of S. sanguis as well as among S. mitis and the two species S. pneumoniae and S. oralis. While iga genes of S. sanguis and S. oralis were highly homogeneous, the genes of S. pneumoniae and S. mitis showed extensive polymorphism reflected in different degrees of antigenic diversity.

Amino Acid Sequence↗

Side effects associated with pneumococcal vaccination.

BACKGROUND: Pneumococcal disease is a major cause of morbidity and death, especially among elders and other people at high risk. In spite of long-standing national recommendations for its use, pneumococcal vaccine is underused, with 70% or more of targeted persons as yet unimmunized. Concern about side effects is a barrier to successful vaccine delivery. METHODS: Persons attending a walk-in pneumococcal vaccination clinic were surveyed by use of structured telephone interviews. They were asked about health characteristics and local and systemic symptoms experienced during the week after their vaccination (postvaccination period). These responses were compared with the symptoms they reported for the 7 days immediately preceding their interview (the comparison period). RESULTS: A total of 1006 persons were interviewed a mean of 65.4 days after their vaccination. They had an average age of 69.9 years, and approximately 95% were in a high-risk group targeted for pneumococcal vaccination. For all systemic symptoms including fever, rash, myalgias, fatigue, malaise, and headache, subjects reported similar or lower rates during the postvaccination week than during the comparison week. Local reactions occurred in 28.2% of subjects. These local symptoms were mild to moderate for more than 90% of subjects and rarely resulted in the need to decrease the use of their arm. CONCLUSION: Pneumococcal vaccination was not associated with an increase in systemic symptoms but was associated with mild to moderate local symptoms in about one fourth of vaccine recipients. These findings should help health care providers and their patients address an important barrier to pneumococcal immunization.

Aged↗

Influenza vaccination of healthcare workers.

OBJECTIVE: To assess factors associated with influenza vaccination of healthcare workers. DESIGN: Cross-sectional survey. SETTING: University-affiliated Veterans' Affairs medical center. PARTICIPANTS: Staff physicians and nurses employed by the medical center. METHODS: A mailed, self-administered questionnaire. RESULTS: The response rate was 38.0%. The mean age of the respondents was 43.6 years, 71.5% were females, and 26.2% were physicians. Nearly all of the practitioners had daily or weekly contact with elderly or high-risk patients. The influenza vaccination rate of the respondents was 61.2%. More than 50% of vaccine recipients indicated that avoiding illness, protecting patients, and being able to receive the vaccine conveniently and free of charge all were very important factors influencing their decisions to receive the vaccine. Avoiding illness was rated the most important factor by 58.8% of vaccine recipients. Among vaccine nonrecipients, concern about side effects was identified as a very important factor by 36.2% and as the most important factor by 30.9%. Vaccine recipients were significantly more likely than were vaccine nonrecipients to indicate that influenza and its complications are very serious for high-risk patients. They also were more likely to report that the vaccine is very effective, that influenza vaccination is uncommonly associated with side effects, that healthcare workers' risk for contracting influenza is higher than the general public's risk, and that it is very important for healthcare workers to receive the vaccine to decrease risk for transmission to high-risk patients. After stepwise logistic regression, variables independently associated with receipt of vaccine were age, prior receipt of vaccine, being a physician, considering the vaccine to be very effective, believing that systemic side effects are uncommon, and indicating that it is very important for healthcare workers to receive vaccine for the protection of their patients. CONCLUSION: Many healthcare workers fail to receive influenza vaccine each year. Strategies to improve immunization levels should address concerns about vaccine safety and efficacy, barriers to vaccination including inconvenience and cost, and the reasons for targeting healthcare workers.

Adult↗

Side effects associated with influenza vaccination in healthy working adults. A randomized, placebo-controlled trial.

BACKGROUND: Concern about side effects is a barrier to influenza vaccination. This randomized, double-blind, placebo-controlled trial assessed side effects following vaccination among healthy working adults. METHODS: Healthy working adults were recruited during October and November 1994 and were randomized to receive influenza vaccine or placebo injections. Local and systemic symptoms during the week following the injection were evaluated through structured telephone interviews. RESULTS: Of 849 subjects enrolled in the study, 425 received a placebo and 424 received influenza vaccine. Baseline characteristics were similar between the groups, and 99% of subjects completed interviews to assess side effects after the study injection. No differences were seen between the 2 groups for the systemic symptoms of fever, myalgias, fatigue, malaise, or headaches. Overall, 35.2% of placebo and 34.1% of vaccine recipients reported at least 1 of these systemic symptoms (P = .78, chi 2). Vaccine recipients reported a higher rate of arm soreness at the injection site than did placebo recipients (63.8% vs 24.1%, P < .001). Local reactions were mild in both groups and infrequently resulted in decreased use of the arm. After logistic regression, female sex (odds ratio [OR], 1.5;95% confidence interval [CI], 1.1-2.1), age younger than 40 years (OR, 1.6;95% CI, 1.2-2.2), and coincidental upper respiratory tract illness (OR, 4.6; 95% CI, 3.2-6.6) were independently associated with higher rates of systemic symptoms. In the multivariate model, vaccine again was not associated with systemic symptoms (OR, 0.9; 95% CI, 0.7-1.2). CONCLUSIONS: Influenza vaccination of healthy working adults is not associated with higher rates of systemic symptoms when compared with placebo injection. These findings should be useful to physicians and other health care providers as they counsel patients to take advantage of an important opportunity for disease prevention and health protection.

Adult↗

Factors associated with influenza and pneumococcal vaccination behavior among high-risk adults.

OBJECTIVE: This cross-sectional survey assessed factors associated with influenza and pneumococcal vaccination behaviors among high-risk patients exposed to highly organized vaccination programs. INTERVENTIONS: Self-administered questionnaires were mailed to 700 patients randomly selected from the outpatient roster of the medical center. Questions were asked about patient demographic and health characteristics in addition to their knowledge and attitudes regarding influenza and pneumococcal diseases and vaccines. MAIN RESULTS: After three mailings, the response rate was 68%, and 80% of these respondents were in a high-risk ++group. Influenza and pneumococcal vaccination rates for high-risk respondents were 74.4% and 62.5%, respectively. Factors independently associated with both influenza and pneumococcal vaccination behaviors included health care providers' recommendations and having positive attitudes toward immunization. In addition, for influenza vaccination, willingness to comply with the provider's recommendation was also associated with receipt of the vaccine while cigarette smoking was associated with failure to receive the vaccine. CONCLUSIONS: Emphasis on provider recommendations and the knowledge and attitudes of patients may enhance influenza and pneumococcal vaccination rates, even in the context of organized vaccination programs.

Age Factors↗

Population structure of Streptococcus agalactiae reveals an association between specific evolutionary lineages and putative virulence factors but not disease.

To evaluate the genetic diversity and relationships in a collection of 85 Danish strains of Streptococcus agalactiae (group B streptococcus) we have performed restriction fragment length polymorphism analysis on EcoRI- and MspI-digested whole-cell DNA using as probes rRNA, DNA fragments representing the genes encoding hyaluronidase, C5a-peptidase, alpha-antigen, and beta-antigen as well as two randomly selected genomic DNA fragments for which the coding potential is unknown. In addition, we have assayed for expression of hyaluronidase activity and beta-antigen. Combined analyses of our data and those previously obtained by multilocus enzyme electrophoresis and serotyping revealed a population separating into six major lineages that correlate with individual serotypes. The significant linkage disequilibrium of alleles indicates that the S. agalactiae population examined is predominantly clonal. Notably, strains expressing the serotype III capsule divide into two distant evolutionary lineages, of which one lacks expression of hyaluronidase activity. Six North American isolates of serotype III clustered together with multiple Danish serotype III strains, showing that the combinations of characters on which the phylogenetic tree was based are conserved worldwide. Occurrence of beta-antigen correlated with a specific version of the alpha-antigen gene and was exclusively associated with a single major phylogenetic lineage. Comparisons with the clinical history of the strains revealed no evidence of differences in pathogenic potential among the six major genetic divisions.

Adhesins, Bacterial↗

The effectiveness of vaccination against influenza in healthy, working adults.

BACKGROUND: Although influenza causes substantial morbidity and mortality in all age groups, current recommendations emphasize annual immunization for people at high risk for complications of influenza. We conducted a double-blind, placebo-controlled trial of vaccination against influenza in healthy, working adults. METHODS: In the fall of 1994, we recruited working adults from 18 to 64 years of age from in and around the Minneapolis-St. Paul area and randomly assigned them to receive either influenza vaccine or placebo injections. The primary study outcomes included upper respiratory illnesses, absenteeism from work because of upper respiratory illnesses, and visits to physicians' offices for upper respiratory illnesses. The economic benefits of vaccination were analyzed by estimating the direct and indirect costs associated with immunization and with upper respiratory illnesses. RESULTS: We enrolled a total of 849 subjects. Baseline characteristics were similar in the two groups. During the follow-up period, consisting of the 1994-1995 influenza season (December 1, 1994, through March 31, 1995), those who received the vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo (105 vs. 140 episodes per 100 subjects, P < 0.001), 43 percent fewer days of sick leave from work due to upper respiratory illness (70 vs. 122 days per 100 subjects, P = 0.001), and 44 percent fewer visits to physicians' offices for upper respiratory illnesses (31 vs. 55 visits per 100 subjects, P = 0.004). The cost savings were estimated to be $46.85 per person vaccinated. CONCLUSIONS: Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults.

Adolescent↗

An epidemiological study of congenital anorectal malformations: 15 Danish birth cohorts followed for 7 years.

In the county of Fyn (about 500,000 inhabitants) which is a well defined and representative 10% sample of the total Danish population, 15 total birth cohorts were scrutinized for the occurrence of anorectal malformations (ARM). All the patients were followed until the age of 7 or death. In a total of 96,073 births, 29 cases were observed; one concordant monozygotic pair was counted as one case. The study showed the point prevalence at birth to be 3.0 per 10,000; almost the same frequency has been found in Sweden whereas other figures from Europe and North America are lower. Children with ARM have in general a poor prognosis, largely due to the many associated anomalies. In this material, 11 of 12 isolated ARM cases survived until age 7, but five of these had significant handicaps. Out of 17 probands with associated anomalies, only seven survived until age 7, all of them having some handicap. This group of patients spent at least 15 times more days in hospital than an age-matched group from the same region until age 7, and they underwent a considerable number of operations. The study showed an increased frequency of chromosome anomalies among children with ARM.

Abnormalities, Multiple↗

Evaluation of zygosity diagnosis in twin pairs below age seven by means of a mailed questionnaire.

The mothers of a consecutive series of 125 same sexed pairs of twins aged 6 months to 6 1/2 years completed a mailed questionnaire concerning the physical similarity of the twin partners. Zygosity diagnoses were first determined blindly on the basis of the answers given by the mothers, who did not know the result of the blood group test when fulfilling the questionnaire. Next, the results were compared with the zygosity determination based on examination of erythrocyte-, serum- and enzyme-groups. It turned out that a few simple questions distinguished well enough between MZ and DZ pairs, with a frequency of misclassification of 4%, leaving 5% as unclassifiable. It is concluded that twin zygosity can be estimated by a simple questionnaire with sufficient accuracy even in very young twin pairs. This has relevant implications for more extensive twin studies where the use of a wide spectrum of serological characters would imply too high expenses.

Blood Group Antigens↗

Osteogenesis imperfecta: a genetic, radiological, and epidemiological study.

The point prevalence at birth of osteogenesis imperfecta was estimated by a systematic search of all children born 1. I. 1970 to 31. XII. 1983 in the county of Fyn (Denmark). Additionally, the population prevalence on 31. XII. 1983 of all patients with osteogenesis imperfecta in this county was determined. The county is a well-defined, representative subregion of Denmark which demographically comprises a cross-section including about 9% of the Danish population. Altogether, the study disclosed 48 patients with osteogenesis imperfecta. Of these, 17 patients were born 1. I. 1970 to 31. XII. 1983 and 12 had type I, 2 had type II, 2 had type III, and 1 had type IV. Thus, the point prevalence at birth was 21.8/100,000 and the population prevalence was 10.6/100,000 inhabitants. There was great variation in the clinical manifestations within and between the types.

Child↗

Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey.

The point prevalence at birth of generalised bone dysplasias was estimated by a study of all children born between 1 January 1970 and 31 December 1983 in the county of Fyn (Denmark). Additionally the population prevalence on 31 December 1983 of all patients with generalised bone dysplasias in this county was determined. The county is a well defined, representative subregion of Denmark which demographically comprises a cross section of about 9% of the Danish population. In total, bone dysplasias were found to be more frequent than generally assumed. Achondroplasia was, however, less common with a point prevalence at birth of 1.3 per 100,000, while osteogenesis imperfecta (21.8), multiple epiphyseal dysplasia tarda (9.0), achondrogenesis (6.4), osteopetrosis (5.1), and thanatophoric dysplasia (3.8) were found more frequently. It is striking how many bone dysplasias are still erroneously classified as achondroplasia. Correct diagnosis is important for a valid prognosis, for treatment, and for genetic counselling. The diagnosis relies almost exclusively on the radiographical findings.

Bone Diseases, Developmental↗

Dyssegmental dysplasia in siblings: prenatal ultrasonic diagnosis.

Two cases of dyssegmental dysplasia (type Silverman-Handmaker) in siblings are presented. The first-born died at the age of 3 months and the second fetus was followed during pregnancy with ultrasound examinations. In the 20th week of gestation marked shortening of the extremities was found; a female infant showing the same radiologic bony malformations as the firstborn was born by cesarean section. These cases support the autosomal recessive inheritance and demonstrate the possibility of prenatal diagnosis in this type of micromelic dwarfism.

Bone Diseases, Developmental↗

Cystic fibrosis in Denmark 1945 to 1985. An analysis of incidence, mortality and influence of centralized treatment on survival.

The entire population of cystic fibrosis (CF) patients in Denmark diagnosed in the period January 1, 1945, to June 30, 1985, comprised 514 persons of whom 62 were diagnosed at autopsy. Of the remaining 452 patients, 372 were probands and 80 were secondary cases. The effect of a centralized treatment on the prognosis was evaluated using a Cox's regression model. Furthermore an incidence analysis was performed using probands including autopsies. Centralized treatment had a significantly beneficial effect on the prognosis (p = 0.02), the death intensity (hazard rate) being decreased by a factor of 0.60. It was calculated that at present 1 out of 4,760 newborn Danes may be diagnosed as suffering from CF before the age of 15 years, and 3% of the Danish population are heterozygotes for CF.

Adolescent↗

A cohort study of neural tube defects (NTD) in Denmark covering the first seven years of life.

In the County of Fyn, Denmark, which is a well-delimited region comprising a 10% representative sample of the total population, ten complete one year cohorts of newborn were scrutinized for neural tube defects (NTD). Among 66,000 births, 71 cases with NTD were observed. The total prevalence at birth was 1.08/1,000; 0.29 for anencephaly; 0.20 for encephalocele, and 0.59 for spina bifida (SB). This is at the same level as in other Scandinavian countries. Considering only neonates born alive, 57% of the total survived until the age of 7 years, disregarding anencephaly, but only 4 of 18 SB cases and 6 of 11 encephalocele cases had no handicaps at age 7. On the average, SB patients spent 9% of their life before the age of 7 years in hospitals and encephaloceles 2%. The SB cases occupied 25 times more beds per year than the comparable age group in general and many were likely to need continued medical and social care.

Anencephaly↗

The incidence and prevalence of familial polyposis coli in Denmark.

Based on the Danish Polyposis Register, the frequency of familial polyposis coli was estimated at the end of 1982. The mean annual incidence rate of polyposis coli has remained rather constant at approximately 1 X 10(-6) X yr-1 since the forties. The life-time risk of developing polyposis coli is about 1 X 10(-4). The point prevalence rate was 26 X 10(-6) at the end of 1982. The number of cases found in sibs and children of probands made it probable that a nation-wide prophylactic examination of first degree relatives resulted in a complete identification of affected family members. The completeness of the Danish Polyposis Register in the period 1976-82 was estimated to be 90% and the validity of the diagnosis is considered to be 100%.

Adolescent↗

Facial clefts in sibs and children of epileptic patients.

The prevalence of facial clefts in sibs and children of 2,072 epileptics ascertained in a defined region was determined by record linkage with a national cleft register, which also provided expected figures. Observed/expected ratios were increased only for cleft lip with or without cleft palate if the mother had manifested epilepsy: it was 4.7 when anticonvulsants were given before and during pregnancy, 2.7 in cases with no treatment, and zero in children born prior to maternal epilepsy. Children of epileptic men and sibs of epileptics showed no increase. The prevalence of isolated cleft palate was not above expectation in any group.

Anticonvulsants↗