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S Holmberg

Publications and source records attributed to S Holmberg.

At least 37 records · Page 2Linked to original sources

A multicenter study of bacterial vaginosis in women with or at risk for human immunodeficiency virus infection.

BACKGROUND: Bacterial vaginosis is a common gynecologic infection that has been associated with a variety of gynecologic and obstetric complications, including pelvic inflammatory disease, postabortal infection and premature delivery. Recent studies suggest that bacterial vaginosis may increase a woman's risk for human immunodeficiency virus (HIV). We undertook this study to assess whether the prevalence and characteristics of bacterial vaginosis differed according to HIV status in high-risk US women. METHODS: Prevalence of bacterial vaginosis was assessed by Gram's stain and clinical criteria for 854 HIV-infected and 434 HIV-uninfected women enrolled in the HIV Epidemiology Research (HER) Study. Multiple logistic regression techniques were used to determine whether HIV infection independently predicted bacterial vaginosis. RESULTS: Almost half (46%) the women had bacterial vaginosis by Gram's stain. The prevalence of bacterial vaginosis was 47% in the HIV-positive women compared with 44% in the HIV-negative women; this difference was not statistically significant (p = 0.36). After adjustment for other covariates, HIV-positive women were more likely than HIV-negative women to have bacterial vaginosis (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.01-1.70) by Gram's stain but not by clinical criteria (OR 1.16; CI 0.87-1.55). Among HIV-positive women, use of antiretroviral drugs was associated with a lower prevalence of bacterial vaginosis (adjusted OR 0.54; Cl 0.38-0.77). CONCLUSIONS: In this cross-sectional analysis of high-risk US women, HIV infection was positively correlated with bacterial vaginosis diagnosed by Gram's stain.

AIDS-Related Opportunistic Infections↗

Blood lipid levels in a rural male population.

OBJECTIVES: Farmers have a low risk for cardiovascular disease, which may be related to a favourable blood lipid profile. In order to study the blood lipid levels and evaluate the effect of other cardiovascular risk factors on the blood lipid profile, this cross-sectional study was made. MATERIAL AND METHODS: A total of 1013 farmers and 769 non-farming rural men in nine different Swedish counties were examined, interviewed, and replied to questionnaires. The inter-relationships between different risk factors were analysed using a multivariate linear regression model. RESULTS: The farmers had a significantly more favourable blood lipid profile than the non-farmers although the total cholesterol levels were almost the same for the two groups. In the total study population there were significant positive relationships between total cholesterol level and body mass index (BMI), diastolic blood pressure and smoking. The high-density lipoprotein (HDL) level was positively related to physical workload and alcohol consumption, and negatively related to BMI, waist/hip ratio and smoking. Triglyceride levels showed a positive relationship to BMI, waist/hip ratio and blood pressure. Differences between farmers and other rural males were seen, especially with respect to the effect of physical activity and psychosocial factors. Among the farmers, a negative correlation between the Karasek-Theorell authority over work index and total cholesterol, the low-density lipoprotein (LDL)/HDL ratio and triglyceride levels was observed. CONCLUSIONS: This study indicated that diet is of minor significance for the blood lipid profile, whereas factors such as physical activity, body weight and the waist/hip ratio, smoking, alcohol consumption, and perhaps psychosocial working conditions are major independent factors affecting the blood lipid profile most prominently among farmers, but also among non-farming rural men.

Age Factors↗

Chromatin-mediated transcriptional regulation by the yeast architectural factors NHP6A and NHP6B.

The Saccharomyces cerevisiae NHP6A and NHP6B proteins are chromatin architectural factors, functionally and structurally related to the mammalian high mobility group (HMG)-1 and -2 proteins, a family of non-sequence-specific DNA binding proteins. nhp6a nhp6b mutants have various morphological defects and are defective in the induced expression of several RNA polymerase II-transcribed genes. We found that NHP6A/B proteins are also required for full induction of the yeast CHA1 gene. Importantly, CHA1 basal level expression is increased 10-fold in an nhp6a nhp6b double deletion mutant. Micrococcal nuclease and DNase I analysis of the CHA1 gene in this strain showed an open promoter structure, characteristic of the activated state of this promoter, even under non-inducing conditions. To address the possible function of the NHP6A/B proteins in chromatin-mediated gene regulation, we performed whole-genome transcriptional profiling of a Deltanhp6a Deltanhp6b yeast strain. Our results suggest that NHP6A/B proteins play an important regulatory role, repressing as well as potentiating expression of genes involved in several cellular processes, and that NHP6A/B control is exerted at the level of the individual gene.

Chromatin↗

[Improved survival after in-hospital cardiac arrest].

Internationally, survival among patients suffering in-hospital cardiac arrest is relatively low and unchanged at about 15%. Our experience at Sahlgrenska Hospital in Göteborg indicates a higher rate. We found survival to be related to the type of arrhythmia initially encountered, the highest rate having been observed among patients in ventricular fibrillation. We also found survival among patients suffering cardiac arrest to be higher in monitored as opposed to non-monitored wards. Whether the improved survival rate observed at Sahlgrenska as compared with international observations among patients suffering cardiac arrest is due to improvements in the organization or to patient selection is not clear. In order to achieve a higher survival rate after in-hospital cardiac arrest an efficient organization in which health care providers are given regular training and feed back is most likely of the utmost importance.

Cardiopulmonary Resuscitation↗

Effect of bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients in Sweden.

BACKGROUND: Information from the Swedish Cardiac Arrest Registry was used to investigate: (a) The proportion of patients suffering an out-of-hospital cardiac arrest who were given bystander cardiopulmonary resuscitation (B-CPR). (b) Where and by whom B-CPR was given. (c) The effect of B-CPR on survival. METHOD: a prospective, observational study of cardiac arrests reported to the Swedish Cardiac Arrest Registry. Analyses were based on standardised reports of out-of-hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of the Swedish population. From 1983 to 1995 approximately 15-20% of the population had been trained in CPR. RESULTS: Of 9877 patients, collected between January 1990 and May 1995, B-CPR was attempted in 36%. In 56% of these cases, the bystanders were lay persons and in 25% they were medical personnel. Most of the arrests took place at home (69%) and only 23% of these patients were given B-CPR in contrast to cardiac arrest in other places where 53% were given CPR. Survival to 1 month was significantly higher in all cases that received B-CPR (8.2 vs. 2.5%). The odds ratio for survival to 1 month with B-CPR was in a logistic regression analysis 2.5 (95% CI 1.9-3.1). CONCLUSIONS: In Sweden, the willingness and ability to perform B-CPR appears to be relatively widespread. More than half of B-CPR was performed by laypersons. B-CPR resulted in a two to threefold increase in survival.

Cardiopulmonary Resuscitation↗

Incidence, duration and survival of ventricular fibrillation in out-of-hospital cardiac arrest patients in sweden.

UNLABELLED: The chance of survival from ventricular fibrillation (VF) is up to ten times higher than those with other cardiac arrest rhythms. To calculate the effect of out-of-hospital resuscitation organisations on survival, it is necessary to know the percentage of cardiac arrest patients initially in VF and the relationship between delay time to defibrillation and survival. AIM: To study the incidence of VF at the time of cardiac arrest and on first ECG, the duration of VF and the relation between time to defibrillation and survival. METHOD: The Swedish Cardiac Arrest Registry has collected standardised reports on out-of-hospital cardiac arrests from ambulance organisations in Sweden, serving 60% of the Swedish population. RESULTS: In 14065 cases of out-of-hospital cardiac arrest collected between 1990 and 1995, resuscitation was attempted in 10966 cases. INCIDENCE: The first ECG showed VF in 43% of all patients. The incidence of VF at the time of cardiac arrest was estimated to be 60-70% in all patients and 80-85% in the cases with probable heart disease. DURATION: The estimated disappearance rate of VF was slow. Thirty minutes after collapse approximately 40% of the patients were in VF. SURVIVAL: Overall survival to 1 month was only 1.6% for patients with non-shockable rhythms and 9.5% for patients found in VF. With increasing time to defibrillation, the survival rate fell rapidly from approximately 50% with a minimal delay to 5% at 15 min. CONCLUSIONS: This study suggests a high initial incidence of VF among out-of-hospital cardiac arrest patients and a slow rate of transformation into a non-shockable rhythm. The survival rate with very short delay times to defibrillation was approximately 50%, but decreased rapidly as the delay increased.

Adolescent↗

Attitudes of trained Swedish lay rescuers toward CPR performance in an emergency. A survey of 1012 recently trained CPR rescuers.

59 years old. Only 1% had attended the course because of their own or a relative's cardiac disease. Ninety-four per cent believed there was a minor to major risk of serious disease transmission while performing CPR. When predicting their willingness to perform CPR in six scenarios, 17% would not start CPR on a young drug addict, 7% would not perform CPR on an unkempt man, while 97% were sure about starting CPR on a relative and 91% on a known person. In four of six scenarios, respondents from rural areas were significantly more positive than respondents from metropolitan areas about starting CPR. In conclusion, readiness to perform CPR on a known person is high among trained CPR rescuers, while hesitation about performing CPR on a stranger is evident. Respondents from rural areas are more frequently positive about starting CPR than those from metropolitan areas.

Adult↗

Possibilities of implementing dispatcher-assisted cardiopulmonary resuscitation in the community. An evaluation of 99 consecutive out-of-hospital cardiac arrests.

AIM: By evaluating tape recordings of true cardiac arrest calls, to judge the dispatchers ability to (a) identify cases as suspected cardiac arrest (CA), (b) give the case the right priority, (c) identify CA cases suitable for dispatcher-assisted, telephone-guided cardiopulmonary resuscitation (T-CPR) and (d) accomplish T-CPR. METHODS: Evaluation of 99 tape recordings of consecutive cases that had been admitted to the two city hospitals in Göteborg after out-of-hospital CA. RESULTS: In 70% of the interviews, the dispatcher demonstrated impeccable behaviour with short, distinct questions, quickly resulting in a decision on how to handle the case. In 30%, serious criticism could be voiced as the dispatcher displayed very stressful behaviour, or omitted to ask important questions such as whether the patient was conscious and breathing. In 21%, the interviews indicated a clear opportunity to perform T-CPR. In another 10%, there was a possibility of performing T-CPR. Only in 8% was T-CPR actually accomplished. CONCLUSIONS: (1) In the majority of the interviews, the quality was very high, while in one-third, serious criticism could be voiced. (2) In our study, only one-third (95% confidence interval, 22-41) of CA cases were suitable for T-CPR, and T-CPR was performed in only 8% of the 99 cases. (3) To optimise the dispatcher ability to identify suspected CA and initiate T-CPR, both medical knowledge and practical training are needed, preferably with protocols for pre-arrival instructions.

Adolescent↗

A comparison between patients suffering in-hospital and out-of-hospital cardiac arrest in terms of treatment and outcome.

AIM: To compare treatment and outcome amongst patients suffering in-hospital and out-of-hospital cardiac arrest in the same community. PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska University Hospital covering half the catchment area of the community of Göteborg (500 000 inhabitants) and all patients suffering out-of-hospital cardiac arrest in the community of Göteborg. Criteria for inclusion were that resuscitation efforts should have been attempted. TIME OF SURVEY: From 1 November 1994 to 1 November 1997. METHODS: Data were recorded both prospectively and retrospectively. RESULTS: In total, 422 patients suffered in-hospital cardiac arrest and 778 patients suffered out-of-hospital cardiac arrest. Patients with in-hospital cardiac arrest included more women and were more frequently found in ventricular fibrillation. The median interval between collapse and defibrillation was 2 min in in-hospital cardiac arrest compared with 7 min in out-of-hospital cardiac arrest (< 0.001). The proportion of patients being discharged from hospital was 37.5% after in-hospital cardiac arrest, compared with 8.7% after out-of-hospital cardiac arrest (P < 0.001). Corresponding figures for patients found in ventricular fibrillation were 56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P < 0.001). CONCLUSION: In a survey evaluating patients with in-hospital and out-of-hospital cardiac arrest in whom resuscitation efforts were attempted, we found that the former group had a survival rate more than four times higher than the latter. Possible strong contributing factors to this observation are: (i) shorter time interval to start of treatment, and (ii) a prepared selection for resuscitation efforts.

Adolescent↗

Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy.

The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia ¿PCP, esophageal candidiasis, and disseminated Mycobacterium avium complex ¿MAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care. Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART. PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care. The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART. Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.

AIDS-Related Opportunistic Infections↗

Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Adult↗

Mutations that cause threonine sensitivity identify catalytic and regulatory regions of the aspartate kinase of Saccharomyces cerevisiae.

The HOM3 gene of Saccharomyces cerevisiae encodes aspartate kinase, which catalyses the first step in the branched pathway leading to the synthesis of threonine and methionine from aspartate. Regulation of the carbon flow into this pathway takes place mainly by feedback inhibition of this enzyme by threonine. We have isolated and characterized three HOM3 mutants that show growth inhibition by threonine due to a severe, threonine-induced reduction of the carbon flow into the aspartate pathway, leading to methionine limitation. One of the mutants has an aspartate kinase which is 30-fold more strongly inhibited by threonine than the wild-type enzyme. The predicted amino acid substitution in this mutant, A406T, is located in a region associated with the modulation of the enzymatic activity. The other two mutants carry an aspartate kinase with reduced affinity for its substrates, aspartate and ATP. The corresponding amino acid substitutions, K26I and G25D, affect residues located in the vicinity of a highly conserved lysine-phenylalanine-glycine-glycine (KFGG) stretch present in the N-terminal part of the aspartate kinase, to which no function has so far been assigned. We suggest that this region is involved in substrate binding. Mutagenesis of a HOM3 region centred in the KFGG-coding triplets generated alleles that determine threonine sensitivity or auxotrophy for threonine and methionine, but not a phenotype associated with a feedback-resistant aspartate kinase, indicating that this region is not involved in the allosteric response of the enzyme.

Alleles↗

Yeast transcriptional regulator Leu3p. Self-masking, specificity of masking, and evidence for regulation by the intracellular level of Leu3p.

Recent work suggests that the masking of the activation domain (AD) of yeast transactivator Leu3p, observed in the absence of the metabolic signal alpha-isopropylmalate, is an intramolecular event. Much of the evidence came from the construction and analysis of a mutant form of Leu3p (Leu3-dd) whose AD is permanently masked (Wang, D., Hu, Y., Zheng, F., Zhou, K., and Kohlhaw, G. B. (1997) J. Biol. Chem. 272, 19383-19392). In a modified two-hybrid experiment, the ADs of both wild type Leu3p and Leu3-dd were shown to interact with the remainder of the Leu3 protein, in an alpha-isopropylmalate-dependent manner. The finding that masking and unmasking proceed apparently normally when full-length Leu3p is expressed in mammalian cells is also consistent with the notion of intramolecular masking. Here we report on the identification of nine missense mutations (all of them suppressors of the Leu3-dd phenotype) that cause permanent unmasking of Leu3p. The nine mutations map to three short segments located within a 140-residue-long region of the C-terminal part of the middle region of Leu3p. These segments may be part of a spatial trap for the AD. We also performed "domain swaps" between Leu3p and Cha4p, a serine/threonine-responsive activator that, like Leu3p, belongs to the family of Zn(II)2Cys6 proteins. We show that AD masking and response to the appropriate metabolic signal only occur when a given AD remains attached to its own middle region; middle region swapping results in constitutively active proteins. Finally, we show that the extent to which Leu3p regulates reporter gene expression depends on the intracellular concentration of Leu3p. The possible physiological significance of this observation is discussed in light of the known regulation of Leu3p by Gcn4p.

Amino Acid Substitution↗

Transcriptional repression of the yeast CHA1 gene requires the chromatin-remodeling complex RSC.

In eukaryotes, DNA is packaged into chromatin, a compact structure that must be disrupted when genes are transcribed by RNA polymerase II. For transcription to take place, chromatin is remodeled via nucleosome disruption or displacement, a fundamental transcriptional regulatory mechanism in eukaryotic organisms. Here we show that the yeast chromatin-remodeling complex, RSC (remodels the structure of chromatin), isolated on the basis of homology to the SWI/SNF complex, is required for proper transcriptional regulation and nucleosome positioning in the highly inducible CHA1 promoter. In the absence of Sth1p/Nps1p (a homolog of Swi2p/Snf2p) or of Swh3p (a homolog of Swi3p), expression of CHA1 in non-induced cells is increased to a level comparable with that of fully induced cells. Furthermore, in non-induced cells depleted for Sth1p/Nps1p or Swh3p, a nucleosome positioned over the TATA box of the CHA1 promoter is disrupted, an architectural change normally only observed during transcriptional induction. In addition, deletion of the gene-specific activator Cha4p did not affect derepression of CHA1 in cells depleted for Swh3p. Thus, CHA1 constitutes a target for the RSC complex, and we propose that RSC is essential for maintaining a repressive chromatin structure at the CHA1 promoter.

Chromatin↗

The problem of out-of-hospital cardiac-arrest prevalence of sudden death in Europe today.

In Europe, 40% of all deaths of individuals who are 25-74 years of age are caused by cardiovascular disease. Cardiac disease is the underlying cause in two-thirds of out-of-hospital sudden deaths. The 28-day case fatality rate for the combined population of out-of-hospital coronary artery disease deaths and hospitalized acute myocardial infarction patients is approximately 50% in 29 of the regions included in the World Health Organization (WHO) Monitoring Trends and Determinants in Cardiovascular Disease registry. Of 14,065 patients included in the Swedish Cardiac Arrest Registry, resuscitation procedures were started in 10,966 patients. The remaining 3,099 were considered definitely dead; 70% were witnessed, cardiac arrests and 32.3% had been given bystander cardiopulmonary resuscitation (CPR). The incidence of ventricular tachycardia (VT)/ventricular fibrillation (VF) in all patients was 43%, in witnessed cases 54%, and in nonwitnessed cases, 31%. The initial incidence of VT/VF was calculated to be approximately 60% in the whole population and 80-85% in those with probable cardiac disease. Survival to 1 month was 5.0% in the total population, 9.5% for those with VT/VF on the first electrocardiogram compared with 1.6% for those not in VT/VF. Survival rate was also calculated in relation to delay time to first defibrillation. Survival was 50% when defibrillation was performed immediately and decreased gradually to 0% for those with a delay time of 20 minutes. The survival rate after bystander CPR was 2.6-fold higher than the rate for those where no treatment was given until the ambulance arrived.

Adult↗

Substrate specificity and gene expression of the amino-acid permeases in Saccharomyces cerevisiae.

All known amino-acid permeases (AAPs) in Saccharomyces cerevisiae belong to a single family of homologous proteins. Genes of 15 AAPs were overexpressed in different strains, and the ability to take up one or more of the 20 common L-alpha-amino acids was studied in order to obtain a complete picture of the substrate specificity for these permeases. Radiolabelled amino-acid uptake measurements showed that Agp1p is a general permease for most uncharged amino acids (Ala, Gly, Ser, Thr, Cys, Met, Phe, Tyr, Ile, Leu, Val, Gln and Asn). Gnp1p, which is closely related to Agp1p, has a somewhat less-broad specificity, transporting Leu, Ser, Thr, Cys, Met, Gln and Asn, while Bap2p and Bap3p, which are also closely related to Agp1p, are able to transport Ile, Leu, Val, Cys, Met, Phe, Tyr and Trp. All four permeases are transcriptionally induced by an extracellular amino acid, but differ in expression with respect to the nitrogen source. On a non-repressive nitrogen source, AGP1 is induced, while GLN1, BAP2 and BAP3 are not. Except for Dip5p, which is a transporter for Glu, Asp, Gln, Asn, Ser, Ala and Gly, the rest of the permeases exhibit narrow specificity. Tat2p can take up Phe, Trp and Tyr; Put4p can transport Ala, Gly and Pro; while Can1p, Lyp1p and the previously uncharacterized Alp1p are specific for the cationic amino acids. These findings modify the prevalent view that S. cerevisiae only contains one general amino-acid permease, Gap1p, and a number of permeases that are specific for a single or a few amino acids.

Amino Acid Transport Systems↗