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Biomedical subjects

S Holmberg

Publications and source records attributed to S Holmberg.

At least 55 records · Page 3Linked to original sources

Prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women. HIV Epidemiology Research Study Group.

This study was undertaken to assess whether the prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive women was higher than among high-risk HIV-seronegative women at their baseline visit for the HIV Epidemiology Research Study. Results were available for 851 HIV-seropositive and 434 HIV-seronegative women. Human papilloma virus (HPV) infection was more prevalent among HIV-seropositive women (64% vs. 28%). Bacterial vaginosis was common (35% vs. 33%), followed by trichomoniasis (12% vs. 10%), syphilis (8% vs. 6%), Chlamydia trachomatis infection (4% vs. 5%), candidal vaginitis (3% vs. 2%), and Neisseria gonorrhoeae infection (0.8% vs. 0.3%). Alcohol use (odds ratio [OR], 1.8; 95% confidence interval [CI], 1. 3-2.4) and smoking (OR, 1.8; 95% CI, 1.3-2.5) were associated with bacterial vaginosis. Bacterial vaginosis (OR, 2.3; 95% CI, 1.5-3.4), trichomoniasis (OR, 2.3; 95% CI, 1.1-4.7), and syphilis (OR, 3.1; 95% CI, 1.3-7.4) were found to be more prevalent among black women. Our study showed no statistically significant difference in the prevalence of lower genital tract infections except for HPV between HIV-infected and demographically and behaviorally similar HIV-uninfected high-risk women.

Adult↗

Nucleosome structure of the yeast CHA1 promoter: analysis of activation-dependent chromatin remodeling of an RNA-polymerase-II-transcribed gene in TBP and RNA pol II mutants defective in vivo in response to acidic activators.

The Saccharomyces cerevisiae CHA1 gene encodes the catabolic L-serine (L-threonine) dehydratase. We have previously shown that the transcriptional activator protein Cha4p mediates serine/threonine induction of CHA1 expression. We used accessibility to micrococcal nuclease and DNase I to determine the in vivo chromatin structure of the CHA1 chromosomal locus, both in the non-induced state and upon induction. Upon activation, a precisely positioned nucleosome (nuc-1) occluding the TATA box and the transcription start site is removed. A strain devoid of Cha4p showed no chromatin alteration under inducing conditions. Five yeast TBP mutants defective in different steps in activated transcription abolished CHA1 expression, but failed to affect induction-dependent chromatin rearrangement of the promoter region. Progressive truncations of the RNA polymerase II C-terminal domain caused a progressive reduction in CHA1 transcription, but no difference in chromatin remodeling. Analysis of swi1, swi3, snf5 and snf6, as well as gcn5, ada2 and ada3 mutants, suggested that neither the SWI/SNF complex nor the ADA/GCN5 complex is involved in efficient activation and/or remodeling of the CHA1 promoter. Interestingly, in a sir4 deletion strain, repression of CHA1 is partly lost and activator-independent remodeling of nuc-1 is observed. We propose a model for CHA1 activation based on promoter remodeling through interactions of Cha4p with chromatin components other than basal factors and associated proteins.

Chromatin↗

A novel esterase from Saccharomyces carlsbergensis, a possible function for the yeast TIP1 gene.

An extracellular esterase was isolated from the brewer's yeast, Saccharomyces carlsbergensis. Inhibition by diisopropyl fluorophosphate shows that the enzyme has a serine active site. By mass spectrometry, the molecular weight of the enzyme was 16.9 kDa. The optimal pH for activity was in the range of four to five. Esterase activity was found in beer before pasteurization, and a low level of activity was still present after pasteurization. Caprylic acid, which is present in beer, competitively inhibited the esterase. The substrate preference towards esters of p-nitrophenol indicated that the enzyme prefers esters of fatty acids from four to 16 carbon atoms. The esterase has lipolytical activity; olive oil (C-18:1), which is a classical substrate for lipase, was hydrolysed. N-terminal sequence analysis of the esterase yielded a sequence which was identical to the deduced amino acid sequence of the S. cerevisiae TIP1 gene. The esterase preparation did not appear to contain significant amounts of other proteins than Tip1p, indicating that the TIP1 gene is the structural gene for the esterase.

Amino Acid Sequence↗

Health services use by urban women with or at risk for HIV-1 infection: the HIV Epidemiology Research Study (HERS).

OBJECTIVE: To characterize health services use by urban women with or at risk for HIV-1 infection enrolled in a prospective multicenter study. METHODS: 1310 women 16 to 55 years of age who were at risk for HIV-1 infection were recruited between April 1993 and January 1995 at four urban centers (Baltimore, Maryland; The Bronx, New York; Detroit, Michigan; and Providence, Rhode Island). HIV-1-seropositive women without AIDS-defining illness were oversampled in a ratio of 2:1 in comparison with HIV-1-seronegative women. At a baseline study visit, the women received physical and laboratory examinations, including CD4+ counts, and were interviewed regarding HIV risk behavior, health services use, and clinical data. RESULTS: 863 women were HIV-1-seropositive and 430 were HIV-1-seronegative. Fifty-two percent of the women reported injection drug use (IDU) since 1985, and 48% acquired HIV through sexual contact. Seventy-seven percent were African American, 23% were white, and 16% were Hispanic. The median age was 35 years. HIV-seronegative women were significantly less likely to have health insurance (19%) than were HIV-seropositive women (30%; p < .001). Among the HIV-seropositive women, 68% had CD4+ cell counts of <500/microl, and 64% were asymptomatic. Sixty-four percent of the HIV-seronegative women had had an outpatient hospital visit in the past 6 months, as had 86% of HIV-seropositive women (p < 0.001). Hospitalization in the past 6 months was also higher in HIV-seropositive women (22% vs. 12%; p < .001). Despite heavy use of health services, only 49% of women with CD4+ counts of <200/microl reported current use of antiretroviral therapy, and only 58% reported current use of Pneumocystis carinii pneumonia (PCP) prophylaxis. Among HIV-seropositive women, and after adjusting for CD4+ count, HIV symptoms, race, and study site, IDUs were significantly less likely to have a regular doctor and a recent outpatient visit and more likely to be hospitalized and use the emergency department (ED) than were non-IDUs. In multivariate analyses of HIV-seropositive persons, African American women had similar access to care and use of antiretroviral therapy and PCP prophylaxis than did white women but were less likely to have an outpatient department visit in the previous 6 months and to be taking PCP and opportunistic infection (OI) prophylaxis. Health services access and use of HIV-related therapies did not significantly differ between Hispanic and white women with HIV infection. CONCLUSION: Although both HIV-seropositive and HIV-seronegative women had high levels of use of medical services, current use of antiretrovirals and OI prophylaxis was low throughout, and IDUs used HIV-related primary health services less and were more likely to receive emergency or episodic care. IDU and African American race were independently associated with decreased use of medical services.

Adolescent↗

Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count.

CONTEXT: Plasma human immunodeficiency virus type 1 (HIV-1) viral load and CD4+ cell count are used to predict prognosis of persons infected with HIV. However, whether combining these markers improves prognostic accuracy and whether they predict prognosis for injection drug users (IDUs) and nonwhite persons infected with HIV has not been extensively investigated. OBJECTIVE: To evaluate plasma viral load and CD4+ cell count as prognostic indicators for the acquired immunodeficiency syndrome (AIDS) and infectious disease deaths. DESIGN: Cohort study initiated in 1988 and 1989 with follow-up for up to 7.9 years. PARTICIPANTS: Injection drug users infected with HIV recruited from the community in Baltimore, Md. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA and CD4+ cell count measured at baseline compared with time to first clinical AIDS diagnosis and death due to an infectious disease. RESULTS: Of 522 subjects, 96% were African American, 80% were male, 96% injected drugs within the past 6 months, and the median age was 33 years. A total of 146 cases of AIDS and 119 infectious disease deaths were seen during a median follow-up period of 6.4 years. Time-fixed baseline levels of viral load and CD4+ cell count were independent predictors of progression to AIDS and infectious disease deaths, but in proportional hazards models, viral load had better predictive value than CD4+ cell count. Kaplan-Meier analysis of time to AIDS and to infectious disease deaths by viral load (<500, 500-9999, 10000-29 999, > or =30000 copies/mL) at 3 levels of CD4+ cell count (<0.20, 0.20-0.49, and > or =0.50x10(9)/L [<200,200-499, and > or =500/microL]) was reduced to a 5-stage classification scheme using a backward stepwise regression procedure. The 5-year cumulative probabilities for AIDS and infectious disease deaths ranged from 0% and 0%, respectively, for group I (viral load, <500 copies/mL; CD4+ cell count, 0.50x10(9)/L) to 81.2% and 76.1% respectively, for group V (viral load, > or =10000 copies/mL; CD4+ cell count, 0.20x10(9)/L). CONCLUSIONS: In this study, plasma HIV-1 viral load independently and in combination with CD4+ cell count measurements provided powerful prognostic information for progression to AIDS and death caused by infectious disease in a population of predominantly African American IDUs. Combining categories of both markers provided a simple method for prognostically staging HIV disease.

AIDS-Related Opportunistic Infections↗

Dip5p mediates high-affinity and high-capacity transport of L-glutamate and L-aspartate in Saccharomyces cerevisiae.

Genes encoding homologues of known amino-acid permeases were deleted in a strain also deficient in the general amino-acid permease. The uptake capacity of the mutants was investigated for several L-alpha-amino acids. Deletion of a gene denoted DIP5 results in the loss of L-aspartate and L-glutamate uptake. The dip5 mutation caused a several hundred-fold reduction of uptake of the two amino acids, both in cells grown on proline as a nitrogen source and in cells grown on ammonium. DIP5-dependent uptake of L-aspartate and L-glutamate was somewhat lower in ammonium-grown cells than in proline-grown cells. Transcriptional regulation is at least partially responsible for this difference, as shown by assaying the DIP5 promoter fused to lacZ. This suggests that the promoter is subject to nitrogen catabolite repression. Transport of a few other amino acids was moderately affected by dip5 but was not competed by L-aspartate in the DIP5 parental strain; transport of these amino acids is therefore unlikely to be mediated by Dip5p. Our results suggest that DIP5 encodes an amino-acid permease with a high transport capacity and a high affinity for L-glutamate and L-aspartate, with a Kt of about 50 microM for both.

Amino Acid Transport Systems↗

Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild-type ILV1 promoter and interacts synergistically with Reb1p.

A cis-acting element required for GCN4-independent basal-level transcription of ILV1 was previously identified in our laboratories as a binding site for the REB1 protein (Reb1p). Further deletion analysis of the ILV1 promoter region identified a second element also required for GCN4-independent basal-level ILV1 expression. This second element is an A.T-rich tract (26 As out of 32 nucleotides) situated 15 bp downstream of the Reb1p-binding site. Deletion of both the Reblp site and the poly(dA:dT) element totally eliminates basal activity of the ILV1 promoter. We show that the two elements act synergistically to control ILV1 expression and that the synergistic effect is distance dependent. We demonstrate that (i) datin (Dat1p), the only known poly (dA:dT)-binding protein in yeast, specifically binds to the ILV1 poly(dA:dT) element in vitro; (ii) Dat1p functions as a trans-activating factor in the ILV1 context; and (iii) the synergistic activation observed in vivo between the Reb1p site and the poly(dA:dT) element depends on the presence of the structural gene for Dat1p, DAT1.

Base Sequence↗

Survival after cardiac arrest outside hospital in Sweden. Swedish Cardiac Arrest Registry.

The voluntary Swedish Cardiac Arrest Registry has collected and analyzed 14,065 standardised reports on cardiac arrests up until May 1995. The reports have been collected from approximately half of Sweden's ambulance districts, which cover 60% of the population. Resuscitation was attempted in 10,966 cases. The median age was 70 years. In 70.0% the arrest was witnessed, and in 43.3% the first recorded rhythm was VT/VF. Bystander-CPR was initiated in 32.3% of the cases. Most cardiac arrests took place at home (65.8%) and 67.1% were judged to be of cardiac origin. In 1692 cases (15.4%), the patient was admitted alive in hospital and 544 patients (5.0%) were alive after 1 month. Survival to 1 month in the subgroup which presented with VT/VF was 9.5%. We found no significant difference between survival in large cities and smaller communities. The survivors were analysed in relation to time to defibrillation and we found a strong correlation between a short time and increased survival.

Aged↗

Factors surrounding cardiopulmonary resuscitation influencing bystanders' psychological reactions.

The incidence of Sweden's out-of-hospital cardiac arrests averages 10000 annually. Each year bystanders initiate cardiopulmonary resuscitation (CPR) approximately 2000 times prior to arrival of emergency medical service (EMS). The aim of this study was to identify factors influencing the bystanders psychological reactions to performing CPR. We mailed a questionnaire to all bystanders who reported performing CPR to the CPR Centre of Sweden from autumn 1992 to 1995. The study included 544 bystander reports. Nine factors were found to be associated with bystanders experience in a univariate analysis. Among these were victim outcome (p < 0.0001), CPR duration (p = 0.0009) and their experience of the attitude of the EMS personnel (p = 0.004). In a multivariate logistic regression model, lack of debriefing following the intervention (p = 0.0001) and fatal victim outcome (p = 0.03) were independent predictors of a negative bystander psychological reaction. The importance of having someone to talk to following an intervention and the EMS personnel concern for the rescuer should be emphasised. The goal should be that critical incident debriefing is available to every bystander following his or her CPR attempt.

Attitude of Health Personnel↗

Jaw lift--a simple and effective method to open the airway in children.

Assessment of breathing during resuscitation of children is important. Misjudgement due to failure to open the airway may lead to mouth-to-mouth ventilation in unconscious children who have retained spontaneous breathing efforts, and might lead to completely ineffective ventilation with gastric distension. The efficiency of the standard head tilt-chin lift manoeuvre (HT-CL) and the jaw lift manoeuvre (JL) for opening of the airway in children was investigated. Fifty children between 1 and 9 years of age breathing spontaneously during deep anaesthesia were studied. Both manoeuvres were randomly performed in all children by nurse anaesthetists. The time for opening and the quality of the airway was determined by a blind folded anaesthesiologist listening to the breathing sounds. The standard HT-CL manoeuvre was insufficient in 12% of the children. JL was more effective than HT-CL in opening the airway in unconscious children who had retained attempts at spontaneous breathing. The JL manoeuvre may, therefore, be recommended in situations when the HT-CL manoeuvre is insufficient.

Age Factors↗

Ventilation Flow Organization for Efficient Elimination of Contaminated Air.

Displacement ventilation and well-organized ventilation flow structures are emphasized. Perhaps the biggest advantage of displacement ventilation is its increased effectiveness in removing pollutants from a ventilated space and the efficient use of ventilation air. Several questions on how the systems should be designed to achieve optimal efficiency are still unanswered. Small variations in room geometries and air supply arrangements can totally change the conditions. Results from this investigation show the importance of an even distribution of the incoming supply air, numerically calculated age-of-air values and the influence of residual tracer concentrations on measured mean values for the age of air.

Journal Article↗

Treatment of primary liver cancer.

OBJECTIVE: To evaluate treatment of patients with primary liver cancer. DESIGN: Prospective protocol including subsets of randomised studies. SETTING: University hospital, Sweden. SUBJECTS: 123 patients with primary liver cancer. INTERVENTIONS: 64 patients underwent hepatic resection, 25 were included in a trial of adjuvant chemotherapy. 24 further patients whose tumours were not resectable were included in a trial of intra-arterial infusion of doxorubicin. MAIN OUTCOME MEASURES: Survival and postoperative morbidity. RESULTS: The median survival time for patients who had had resections was 11 months (range 0-111). Twelve per cent survived more than 5 years. No prognostic factor had any significant effect on outcome. The postoperative mortality was 11% (7/64). The patients allocated to adjuvant chemotherapy survived a median of 10 months (range 1-47) and the controls 29 months (range 8-111) (p=0.04). Patients with unresectable liver cancer treated with intra-arterial doxorubicin lived no longer than untreated controls (median 8 months (range 1-56) compared with 7 months (range 1-28)). CONCLUSIONS: Treatment of patients with primary liver cancer is still an unsolved problem. Adjuvant chemotherapy with doxorubicin had no beneficial effect on survival.

Adult↗

Reported health status among farmers and nonfarmers in nine rural districts.

Farmers appear to have a lower morbidity and mortality rate than other occupational groups. Whether this better health is due to exposure to farming or to the well-known fact that rural populations have better health than urban ones, irrespective of occupation, is not clear. To explore this problem, all male farmers in nine administrative areas and age-matched nonfarmers from the same rural areas were sampled and invited to participate in a survey. 1782 (76%) men responded. We found that farmers had somewhat lower rates of outpatient health care utilization for causes other than trauma and fewer hospital admissions. These differences were independent of the urban-rural factor and could not be explained by traditional determinants of health and health care utilization. Other factors, linked to farming or to farmers' lifestyles, are probably involved.

Adult↗

Randomised trial of elective stenting after successful percutaneous transluminal coronary angioplasty of occluded coronary arteries.

BACKGROUND: The value of angioplasty in occluded coronary arteries is limited by a restenosis/reocclusion rate of 50-70%. In patients with subtotal occlusion, stent implantation has been shown to reduce clinical and angiographic restenosis. Retrospective observational studies have suggested that stenting could reduce restenosis in total occlusions. The value of sustained coronary patency on global and regional left ventricular function in this clinical setting has not been defined clearly. OBJECTIVES: To assess the medium term effect of elective intracoronary stent deployment after successful percutaneous transluminal coronary angioplasty (PTCA) of an occluded coronary artery. METHODS: Sixty patients with a total coronary occlusion successfully treated by PTCA were randomised to receive an intracoronary stent or no stent. Patients underwent clinical and angiographic follow up at six months. RESULTS: Thirty patients received a stent (group A) and 30 were treated by angioplasty alone (group B), all with initial success. One patient in group B required repeat angioplasty with stenting at 24 hours and one patient died after 10 days. Angiographic follow up was available for 57 patients. This showed a significantly reduced reocclusion rate in group A compared with group B (7% v 29%, p < 0.01) and a tendency to a reduced restenosis rate (22% v 40%, p = 0.105) in patients with no reocclusion. Left ventricular function, both global and regional, improved in group A. Only the regional left ventricular function in the area supplied by the target coronary artery improved in group B. Recurrence of symptoms and clinical events such as repeat angioplasty, coronary artery bypass grafting, death or myocardial infarction tended to be reduced in group A (4 (13%) v 9 (30%)). CONCLUSIONS: Intracoronary stent insertion is effective in reducing the rate of reocclusion and shows a trend towards reduced restenosis after opening of a total coronary occlusion by balloon angioplasty. Sustained patency of the target coronary artery is associated with improvement in global and regional left ventricular function.

Adult↗

Prevalence of antibodies specific to Puumala virus among farmers in Sweden.

OBJECTIVES: The Puumala virus is the causative agent of nephropathia epidemica, a European form of hemorrhagic fever with a renal syndrome. From its reservoir in bank voles, the virus is spread by airborne transmission to humans. Occupational risks for the acquisition of nephropathia epidemica are not well defined. The prevalence of serum antibodies to Puumala virus was determined for Swedish farmers. From a comparison of the prevalence among farmers from various parts of the country, the assumption that Puumala virus occurs endemically only in the northern and central parts of Sweden was also tested. METHODS: Serum samples from 910 farmers and 663 referents living in various rural parts of Sweden were tested with an enzyme-linked immunosorbent assay, using a recombinant nucleocapsid protein of Puumala virus as the antigen. RESULTS: North of a latitude of 59 degrees N, the prevalence of Puumala virus antibodies was significantly higher among farmers (12.9%) than among referents (6.8%). In the southern areas, antibodies to Puumala virus were rare, and altogether only 2 of 459 persons had antibodies. Seropositive persons did not differ from seronegative ones with regard to blood pressure, and they did not comprise cases of chronic renal disease. CONCLUSIONS: Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.

Adult↗