Biomedical subjects

H Pfister

Publications and source records attributed to H Pfister.

At least 19 recordsLinked to original sources

PubMed2006

Interferon regulatory factor 5.2 acts as a transcription repressor of Epidermodysplasia verruciformis-associated human papillomaviruses.

Human papillomavirus type 8 (HPV8) poses a high risk for malignant conversion of skin lesions in patients with Epidermodysplasia verruciformis (Ev). Its oncogene promoter P(175) contains the conserved sequence motifs CCAAC, M29, and an A/T-rich region, which are common in many Ev-associated viruses. In human keratinocytes P(175) shows very weak activity. We used the M29 sequence as bait in a yeast-one-hybrid screen of a HaCaT cDNA library to identify interacting proteins regulating P(175). We report the identification of a cDNA encoding the interferon regulatory factor IRF5.2. In band shift assays the physical interaction of IRF5.2 and M29 was confirmed, and also its binding to the negative regulatory element (NRE) of HPV8 could be demonstrated. In transient reporter gene assays, overexpressed IRF5.2 acts as a transcriptional repressor of HPV8 and the Ev-associated HPV types 5, 14, and 25. These results indicate that the cellular transcription factor IRF5.2 is a general transcription repressor of Ev-associated HPV.

Alphapapillomavirus↗

PubMed2006

E7 proteins from high- and low-risk human papillomaviruses bind to TGF-beta-regulated Smad proteins and inhibit their transcriptional activity.

Human papillomaviruses (HPV) infect keratinocytes of skin and mucosa. Persistent infection can lead to the formation of benign tumors. In cases of high-risk HPV, such as HPV16 or 18, these may further progress to cancer. In order to support viral replication in suprabasal keratinocytes, the HPV E7 protein employs various strategies to keep keratinocytes in cycle and counteracts anti-proliferative signals from outside. HPV16 E7 can directly interfere with transforming growth factor-beta (TGF-beta) signalling by binding to Smad proteins mediating growth arrest. It has been speculated that this property of HPV16 E7 contributes to HPV-associated carcinogenesis. Here, we show that E7 proteins from different low- and high-risk HPV types bind to Smad 1 to 4. The E7 protein from HPV1, a low-risk HPV causing plantar warts, efficiently inhibited Smad 3-induced transcription. Our data strongly indicate that the Smad-binding capacity of E7 proteins from different HPVs may preserve keratinocyte proliferation required for the productive viral life cycle rather than promoting carcinogenesis.

Cell Proliferation↗

PubMed2005

"Anxietas tibiarum". Depression and anxiety disorders in patients with restless legs syndrome.

BACKGROUND: Symptoms of anxiety and depression in patients with restless legs syndrome (RLS) have been observed. However, it is unclear whether rates of threshold depression and anxiety disorders according to DSM-IV criteria in such patients are also elevated. METHODS: 238 RLS patients were assessed with a standardized diagnostic interview (Munich-Composite International Diagnostic Interview for DSM-IV) validated for subjects aged 18-65 years. Rates of anxiety and depressive disorders were compared between 130 RLS patients within this age range and 2265 community respondents from a nationally representative sample with somatic morbidity of other types. RESULTS: RLS patients revealed an increased risk of having 12-month anxiety and depressive disorders with particularly strong associations with panic disorder (OR=4.7; 95% CI=2.1-10.1), generalized anxiety disorder (OR=3.5; 95% CI= 1.7-7.1), and major depression (OR=2.6; 95% CI=1.5-4.4). In addition, lifetime rates of panic disorder and most depressive disorders as well as comorbid depression and anxiety disorders were considerably increased among RLS patients compared with controls. CONCLUSIONS: The results suggest that RLS patients are at increased risk of having specific anxiety and depressive disorders. Causal attributions of patients suggest that a considerable proportion of the excess morbidity for depression and panic disorder might be due to RLS symptomatology.

Adolescent↗

PubMed2004

Prevalence, co-morbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS).

BACKGROUND: The German National Health Interview and Examination Survey (GHS) is the first government mandated nationwide study to investigate jointly the prevalence of somatic and mental disorders within one study in the general adult population in Germany. This paper reports results from its Mental Health Supplement (GHS-MHS) on 4-week 12-month, and selected lifetime prevalence of a broad range of DSM-IV mental disorders, their co-morbidity and correlates in the community. METHODS: The sample of the GHS-MHS (n=4181; multistage stratified random sample drawn from population registries; conditional response rate: 87.6%) can be regarded as representative for the German population aged 18-65. Diagnoses are based on fully structured computer assisted clinical interviews (M-CIDI), conducted by clinically trained interviewers. RESULTS: 12-month prevalence for any DSM-IV study disorder is 31% (lifetime: 43%; 4-week: 20%) with anxiety disorders, mood disorders and somatoform syndromes being the most frequent diagnoses. Retrospective age of onset information reveals that most disorders begin early in life. Co-morbidity rates among mental disorders range from 44% to 94%. Correlates of increased rates of mental disorders and co-morbidity were: female gender (except for substance disorders), not being married, low social class, and poor somatic health status. Health care utilization for mental disorders depended on co-morbidity (30% in 'pure', 76% in highly co-morbid cases) and varied from 33% for substance use disorders to 75% for panic disorder. CONCLUSIONS: Results confirm and extend results from other national studies using the same assessment instruments with regard to prevalence, co-morbidity and sociodemographic correlates, covering a broader range of DSM-IV disorders [i.e. somatoform disorders, all anxiety disorders (except PTSD), mental disorders due to substance or general medical factor, eating disorders]. Intervention rates were higher than in previous studies, yet still low overall.

Adolescent↗

PubMed2004

2',5'-Oligoadenylate synthetase activity analysis and human papilloma virus typing as prognostic factors in patients with recurrent respiratory papillomatosis.

OBJECTIVE: Determination of early prognostic factors in patients with recurrent respiratory papillomatosis is extremely important, so the major goal of our prospective, multicentre study was to evaluate (1) the feasibility of various factors to determine prognosis of the clinical course, as well as (2) the response to interferon-alpha therapy in recurrent respiratory papillomatosis. METHODS: Forty-two patients with recurrent respiratory papillomatosis were treated with interferon-alpha (3 MU/m(2) three times per week; mean therapy duration was 2.7 +/- 1.8 years) in 1983-1994 and followed-up until 2003. Human papilloma virus (HPV) type, recurrent respiratory papillomatosis severity and 2',5'-oligoadenylate synthetase activity were determined by standard methods and analysed for correlation with the results of long-term clinical outcome. RESULTS AND CONCLUSION: Patients with HPV type 11, a severity score >4, a high number of surgical procedures prior to interferon-alpha therapy and a high basal 2',5'-oligoadenylate synthetase activity should be considered at high risk of an aggressive clinical course, often with spread to lower airway passages, malignant transformation and death. Human papilloma virus type, score for recurrent respiratory papillomatosis severity, number of surgical procedures and 2',5'-oligoadenylate synthetase activity showed significant association with response to interferon-alpha therapy and the long-term clinical course, so these factors have value in predicting prognosis in recurrent respiratory papillomatosis.

2',5'-Oligoadenylate Synthetase↗

PubMed2003

Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts.

Using PCR, the overall prevalence of human papillomavirus (HPV) DNA in penile carcinoma is about 40-45%, which is similar to the detection rate of HPV-DNA in vulvar carcinoma (50%). In analogy to vulvar cancer two different pathways of penile carcinogenesis seem to exist. In contrast to basaloid and warty penile cancers which are regularly HPV-associated (about 80-100%), only a part of keratinizing and verrucous penile carcinomas appear to be related with HPV (33-35%). Penile intraepithelial neoplasias comprising Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis are precursor lesions of basaloid and warty carcinomas of the penis. Precursors of keratinizing carcinomas and verrucous carcinomas are not established. Whether lichen sclerosus and squamous-cell hyperplasia precede penile keratinizing carcinoma is a matter of discussion. Giant condylomata acuminata may precede the development of verrucous carcinomas in some cases. Since high risk HPVs are more frequently found in verrucous carcinomas than in giant condylomas, HPV typing may be a helpful diagnostic step to differentiate giant condyloma from verrucous carcinoma.

Carcinoma in Situ↗

PubMed2003

[Aim, design and methods of the "Hypertension and diabetes screening and awareness" -- (HYDRA) study].

Aim of the study is a comprehensive clinical-epidemiological description of the prevalence of arterial hypertension and diabetes among primary care patients along with an assessment of doctor's recognition rates and prescription behaviour. The paper describes methods and design of the study and provides background information on the sampling process, instruments used as well as characteristics of doctors and patients. The study is based on a nationally representative sample of 1,912 primary care doctors and 45,000 patients that attended the doctors' office on the target days. The patients were also characterized by laboratory tests. The first stage of study consisted of a comprehensive description of the doctors' characteristics in terms of psychosocial, qualification- and provider aspects as well as attitudes towards hypertension and diabetes and their management. In the second stage all patients completed a questionnaire to describe their health behaviour and attitudes as well as the treatment history and therapy. In the third stage all patients were characterized by their doctors in terms of their diagnostic status and their past and current interventions.

Adolescent↗

PubMed2003

[Management of diabetes and hypertension: how do primary care physicians judge their performance?].

With regard to the management of hypertension and diabetes, HYDRA reveals that doctors report multiple problems in their everyday practice. Being confronted with an average of 73 patients a day, with almost every second having either diabetes or hypertension, frequently associated with multiple comorbid conditions, the core obstacle is the time factor. Doctors do not have sufficient time to perform diagnostic tests and especially no time for non-drug interventions of any type. Further available treatment guidelines are only used in 1 out of 2 doctors. Further they seem not to affect doctors performance significantly.

Adult↗

PubMed2003

[Hypertension, diabetes mellitus and comorbidity in primary care].

Almost every second patient seeing a primary care doctor suffers from arterial hypertension and about every fifth has diabetes mellitus. These diseases often occur at the same time. They are associated in more than 80% of the cases with other severe concomitant and subsequent diseases (heart attack, stroke, renal failure, neuropathy etc.). The magnitude especially of subsequent and concomitant diseases, the dimension of the personal suffering and the immense diagnostic and therapeutic challenges for the doctors have been massively underestimated so far. The article informs about the prevalence of the above disease, and structure of the problem. Before the background of an extremely high patient load seen by German General Physicians, the mainstay challenge is highlighted how to achieve further improvements of the quality of care on the basis of scientific guidelines alone, without a concomitant change in the system structure.

Adolescent↗

PubMed2003

Trauma and PTSD - an overlooked pathogenic pathway for premenstrual dysphoric disorder?

BACKGROUND: A recent epidemiological analysis on premenstrual dysphoric disorder (PMDD) in the community revealed increased rates of DSM-IV posttraumatic stress disorder (PTSD) among women suffering from PMDD. AIMS: To explore whether this association is artifactual or might have important pathogenic implications. METHODS: Data come from a prospective, longitudinal community survey of an original sample of N=1488 women aged 14-24, who were followed-up over a period of 40 to 52 months. Diagnostic assessments are based on the Composite International Diagnostic Interview (CIDI) using the 12-month PMDD diagnostic module. Data were analyzed using logistic regressions (odds ratios) and a case-by-case review. RESULTS: The age adjusted odds ratio between PTSD and threshold PMDD was 11.7 (3.0-46.2) at baseline. 10 women with full PTSD and at least subthreshold PMDD were identified at follow-up. Most reported an experience of abuse in childhood before the onset of PMDD. Some had experienced a life-threatening experience caused by physical attacks, or had witnessed traumatic events experienced by others. 3 women reported more than one traumatic event. CONCLUSIONS: A case-by-case review and logistic regression analyses suggest that women with traumatic events and PTSD have an increased risk for secondary PMDD. These observations call for more in-depth analyses in future research.

Adolescent↗

PubMed2003

Recurrent brief depressive disorder reinvestigated: a community sample of adolescents and young adults.

BACKGROUND: This article presents prospective lower bound estimations of findings on prevalence, incidence, clinical correlates, severity markers, co-morbidity and course stability of threshold and subthreshold recurrent brief depressive disorder (RBD) and other mood disorders in a community sample of 3021 adolescents. METHOD: Data were collected at baseline (age 14-17) and at two follow-up interviews within an observation period of 42 months. Diagnostic assessment was based on the Munich Composite International Diagnostic Interview (M-CIDI). RESULTS: Our data suggest that RBD is a prevalent (2.6%) clinical condition among depressive disorders (21.3%) being at least as prevalent as dysthymia (2.3%) in young adults over lifetime. Furthermore, RBD is associated with significant clinical impairment sharing many features with major depressive disorder (MDD). Suicide attempts were reported in 7.8% of RBD patients, which was similar to MDD (11.9%). However, other features, like gender distribution or co-morbidity patterns, differ essentially from MDD. Furthermore, the lifetime co-occurrence of MDD and RBD or combined depression represents a severe psychiatric condition. CONCLUSIONS: This study provides further independent support for RBD as a clinically significant syndrome that could not be significantly explained as a prodrome or residual of major affective disorders.

Adolescent↗

PubMed2003

Primary anxiety disorders and the development of subsequent alcohol use disorders: a 4-year community study of adolescents and young adults.

BACKGROUND: Cross-sectional findings in community surveys of adults suggest that adolescent anxiety disorders are strong predictors of the subsequent onset of alcohol use, abuse and dependence. However, prospective data that follow a sample of adolescents into adulthood are needed to confirm these associations. METHOD: Baseline and 4-year follow-up data from the EDSP-Study, a prospective community survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich, were used. DSM-IV anxiety disorders, alcohol use and alcohol use disorders were assessed with the Munich-Composite-International-Diagnostic-Interview (M-CIDI). Multiple logistic regression analysis, controlling for age, gender, other mental disorders, substance use disorders and antisocial behaviour was used to study the associations of baseline anxiety disorders with the subsequent onset and course of alcohol use and alcohol disorders. RESULTS: Baseline social phobia significantly predicts the onsets of regular use and hazardous use and the persistence of dependence. Panic attacks significantly predict the onsets of hazardous use and abuse as well as the persistence of combined abuse/dependence. Panic disorder significantly predicts the persistence of combined abuse/dependence. Other anxiety disorders do not significantly predict any of the outcomes. CONCLUSIONS: Panic and social phobia are predictors of subsequent alcohol problems among adolescents and young adults. Further studies are needed to investigate the underlying mechanisms and the potential value of targeted early treatment of primary panic and social phobia to prevent secondary alcohol use disorders.

Adolescent↗

PubMed2003

Are patients with pituitary adenomas at an increased risk of mental disorders?

OBJECTIVE: Retrospective clinical studies suggest that patients with pituitary adenoma (PA) have an increased risk of mental disorders. However, empirical evidence for this hypothesis is deficient because of out-dated methodology. Therefore, we investigated the occurrence of mental disorders in 93 patients with PA within a limited time frame of 2 years. METHOD: Patients were subjected to a comprehensive, standardized lifetime and cross-sectional psychopathological symptom and diagnostic assessment, including an evaluation of psychosocial conditions and life events (CIDI, SCL-90) during the past years. RESULTS: We could not find an increased risk of mental disorders as compared with a representative population sample of 481 subjects matched by age and gender. CONCLUSION: As for our random sample, neither suffering from any type of PA nor the extent of the pituitary deficiency represent factors having significant effect on the risk of the subject to develop psychopathology as compared with the general population.

Adenoma↗

PubMed2002

Esophageal cancer in Germany is associated with Epstein-Barr-virus but not with papillomaviruses.

Esophageal squamous cell carcinomas ( n=23) and adenocarcinomas ( n=14) from German patients were tested for the presence of human papillomavirus (HPV) and Epstein-Barr-Virus (EBV) DNA. No DNA for either genital HPV or epidermodysplasia verruciformis-associated HPV was detected in any tumor. In contrast, 35% of squamous cell carcinomas and 36% of adenocarcinomas were shown to contain EBV DNA by nested polymerase chain reaction.

Adenocarcinoma↗

PubMed2002

Variants of the long control region and the E6 oncogene in European human papillomavirus type 16 isolates: implications for cervical disease.

High-risk human papillomavirus types, especially type 16, are risk factors for cervical cancer. Preliminary studies suggest that HPV16 polymorphisms in the long control region or in the E6 gene may alter the oncogenic potential of the virus. This could partially explain why some lesions progress to cancer while others do not. A systematic study combining the long control region and E6 has not been undertaken. This prompted us to investigate the long control region and the E6 in northern European women infected with human papillomavirus 16. We identified the sequence variations of both regions and investigated the long control region promoter activity among various isolates. In addition, we correlated the distribution of long control region and E6 polymorphisms with disease status. We analyzed 45 samples from Swedish and Finnish women. The long control region and the E6 gene were sequenced after polymerase chain reaction long control region fragments of six European isolates covering the majority of polymorphisms in this region were ligated into the pALuc vector and used for luciferase assays. In European HPV16 isolates, polymorphisms in the long control region are more frequent than in the E6 gene. Nevertheless, the promoter function was slightly increased in only one of the tested European long control region variants. In addition, we found a specific European E6 variant, L83V, to be enriched in high-grade lesions and cancer rather than a specific European long control region variant. The difference in oncogenicity between European HPV16 genotypes is more probably due to an altered property of the corresponding E6 proteins rather than to an altered activity of the P97 promoter.

Adult↗

PubMed2002

Parental alcohol use disorders and alcohol use and disorders in offspring: a community study.

BACKGROUND: We examined the association between parental alcohol use disorders and patterns of alcohol consumption and DSM-IV alcohol use disorders in their offspring in a community-based sample of young adults. METHODS: Data are based on baseline and 4-year follow-up data of 2427 respondents aged 14-24 at baseline. Alcohol use and disorders in respondents were assessed using the Munich-Composite-international-Diagnostic-Interview with DSM-IV algorithms. Diagnostic information about parents was collected by family history information from the respondents, and by direct interview with one parent (cohort aged 14 to 17 years only). RESULTS: Although the association between maternal and paternal alcohol use disorders and non-problematical drinking in offspring was minimal, there was a strong effect for the transition to hazardous use and for alcohol abuse and dependence; the effect of parental concordance for transition into hazardous use was particularly striking. Maternal history was associated with a higher probability of progression from occasional to regular use, whereas paternal history was associated with progression from regular to hazardous use. Parental alcoholism increased the risk for first onset of hazardous use and alcohol dependence between the ages of 14-17, and for an earlier onset of the alcohol outcomes in offspring. The impact of parental alcohol use disorders was comparable for male and female offspring. CONCLUSIONS: Parental alcoholism predicts escalation of alcohol use, development of alcohol use disorders and onset of alcohol outcomes in offspring.

Adolescent↗

PubMed2002

Inducible nitric oxide synthase and nitrotyrosine in listeric encephalitis: a cross-species study in ruminants.

Listeria monocytogenes (LM) is a Gram-positive facultative intracellular bacterium that causes fatal meningoencephalitis in humans and ruminants. A current paradigm predicts that intracellular bacteria are controlled by nitric oxide (NO) whose synthesis is catalyzed by inducible nitric oxide synthase (iNOS). The ability of macrophages (Mphi) to express iNOS shows extreme interspecies variability. Here the expression of iNOS and synthesis of NO was studied in listeric encephalitis of cattle, sheep, and goats. iNOS was expressed by a subset of Mphi in cerebral microabscesses in all three species. The level of iNOS expression and the density of cells per lesion expressing iNOS was highest in cattle, intermediate in sheep, and lowest in goats. The accumulation of nitrotyrosine (NT), an indicator of local NO synthesis, was observed in lesions of cattle but not in those of small ruminants. The density of iNOS-expressing cells in lesions was inversely correlated with the number of bacteria. No species differences were observed in regard to reactive oxygen intermediate (ROI) production by stimulated granulocytes, using the flow cytometric dihydrorhodamine-123 (DHR) method indicating ROI generation. Thus, the marked species differences in iNOS expression, NT accumulation, and LM content in lesions of ruminants with listeric encephalitis are explained by different amounts of ROI produced. It suggests that variations in the ability of Mphi to synthesize NO are of pathophysiological significance in listeriosis.

Animals↗

PubMed2001

The natural course of cannabis use, abuse and dependence over four years: a longitudinal community study of adolescents and young adults.

OBJECTIVES: To determine incidence and patterns of natural course of cannabis use and disorders as well as cohort effects in a community sample of adolescents and young adults. METHOD: Cumulative incidence and patterns of cannabis use and disorders were examined in a prospective longitudinal design (mean follow-up period=42 months) in a representative sample (N=2446) aged 14-24 years at the outset of the study. Patterns of cannabis use, abuse and dependence (DSM-IV) were assessed with the Composite International Diagnostic Interview (M-CIDI). RESULTS: (1) Cumulative lifetime incidence for cannabis use (at second follow-up): 47%; 5.5% for cannabis abuse, 2.2% for dependence. (2) Men used and abused cannabis more often than women. (3) The majority of the older participants (18-24 years at baseline) had reduced their cannabis use at follow-up, while younger participants (14-17 years at baseline) more often had increased their use and developed abuse or dependence. (4) The younger birth cohort (1977-1981) tended to start earlier with substance (ab)use compared to the older birth cohort (1970-1977). (5) Cannabis use was associated with increasing rates of concomitant use of other licit and illicit drugs. CONCLUSIONS: Cannabis use is widespread in our sample, but the probability of developing cannabis abuse or dependence is relatively low (8%). The natural course of cannabis use is quite variable: about half of all cannabis users stopped their use spontaneously in their twenties, others report occasional or more frequent use of cannabis.

Adolescent↗