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Biomedical subjects

R Kaiser

Publications and source records attributed to R Kaiser.

At least 109 records · Page 6Linked to original sources
PubMed1998

Role of HIV-1 phenotype in viral pathogenesis and its relation to viral load and CD4+ T-cell count.

The predictive value of HIV-1 phenotype in peripheral blood mononuclear cell (PBMC) coculture and the relation among viral phenotype, viral load, and CD4+ T-cell count were examined in two studies. In study A, 132 HIV-1-infected individuals were examined retrospectively for the relation between the result of their initial HIV cultivation in PBMC coculture and survival rate 6 years later. In study B, 176 patients were examined since 1994 for markers of HIV disease progression. HIV-1 phenotype was determined by PBMC cocultivation, viral load by NASBA HIV RNA QT System, and CD4+ T-cell count by flow cytometry. In study A, the percentage of survival for patients with initial negative virus culture was significantly higher (95%) than in patients with nonsyncytia-inducing (NSI) isolates (78%) and syncytia-inducing (SI) isolates (21%) (P < 0.05 and P< 0.0001, respectively). When SI phenotype was subdivided into moderately cytopathogenic and highly cytopathogenic, significant differences in the rate of survival between these subgroups could be observed (45% vs. 14%; P < 0.05). In study B, progression from negative virus culture to the isolation of NSI variants was associated with increasing viral load (P < 0.0001) but did not affect CD4+ T-cell count significantly (P> 0.07), whereas the switch from NSI to SI virus was accompanied by significant decline of CD4+ T-cells (P < 0.0001) but no change in viral load (P > 0.21). Thus, isolation and phenotyping of HIV represents an additional striking predictive marker for progression of HIV infection.

CD4 Lymphocyte Count↗
PubMed1998

[Indications for appendectomy from the ultrasound-clinical viewpoint].

From 1.1.1993 to 30.9.1997 1149 patients with right-sided abdominal pain were examined by an experienced sonographer. The specificity of the sonographic diagnosis of acute appendicitis was 98.7%, sensitivity 95.6%, PPV 96.5%, NPV 98.3%, OA 97.8%. The negative laparotomy rate in 1996 was 5.4% (appendix not inflamed by histological examination), perforation rate 11.5%. 25 wrong sonographic diagnoses were made. Out of 530 Patients examined 1995 and 1996 181 alternative diagnoses could be made by ultrasonography. Under not corresponding clinical and sonographic results patients were observed in hospital and clinical and sonographic examination were repeated within 6 hours. Under definite positive sonographic result and questional clinical result operation was preferred. Under recurrent attacks of abdominal pain diagnostic laparoscopy was recommended. Sonographic diagnosis of right sided abdominal pain helped to reduce the risk of restricted indication for diagnostic laparoscopy respectively appendectomy by reducing the number of unnecessary operations without relevant change of perforation rate.

Acute Disease↗
PubMed1997

[Air pollution in Switzerland--quantification of health effects using epidemiologic data].

Public health costs ascribable to air pollution are socialized in our society. To quantify the damage to public health, epidemiologic studies are needed. We present the methods and epidemiologic background data which form the basis for estimating the public health effect ascribable to air pollution. The figures are presented per 1 million "average" Swiss population and per 10 micrograms/m3 increase in long-term annual mean particulate pollution (PM10). Quantification was restricted to the health effects given below (due to lack of complete data for other effects or to avoid duplicating health effects which may be described by overlapping measurements). In parenthesis we present (1) the mean effect estimates (+/-1 SE) (% increase per 10 micrograms/m3 increment in PM10) derived from national and international epidemiologic studies, and (2) the expected absolute additional health effects (+/-1 SE) per 1 million Swiss population and per 10 micrograms/m3 increment in PM10, based on Swiss population statistics: total mortality (long-term estimates from the 2 US cohort studies) (+4.4% [+/-1.1]/349 [+/-91] premature deaths per year); prevalence of chronic bronchitis in adults (+25% [+8.4]/increase in long-term prevalence by 3,513 [+/-1.475]); bronchitis among children (35% [+/-13]/5,180 [+/-2,590] additional children sufferers in a year); repeated cough among children (+54% [+/-8.8]/23,490 [+/-5,873] additional children per year); cough/phlegm in adults (+12.8% [+/-7.8]/1.56 [+/-1.08] million person-days per year); hospital admissions for respiratory diseases (+1.47% [+/-0.5]/71 [+/-24] additional admissions or 1,104 (+/-390) hospital days); admissions for cardiovascular diseases (+0.9% [+/-0.25]/70 [+19] admissions; 970 (+/-270) hospital days); restricted activity days (+10.5% [+/-0.77]/0.42 [+/-0.03] million person-days); days with asthma attacks among the 6.7% asthmatics (Swiss prevalence) (+5.3% [+/-2.1]/ 240,000 [+/-102,000] additional person-days). Conservative assumptions were used throughout the study and thus the true effects are likely to be larger. Estimates of Swiss population exposure distribution would be needed to apply these results to the entire population. This step, and monetary quantification of these total effects, were the second and third elements (not shown in this report) of this Swiss government funded project. Although individual relative risks of air pollution are rather slight, the public health burden of even moderate pollution may be substantial.

Adult↗
PubMed1997

CD30 induction and cytokine profiles in hepatitis C virus core-specific peripheral blood T lymphocytes.

Since an efficient control of virus infections may depend on the appropriate lymphokine profile, we studied cytokine responses and CD30 induction, a recently proposed surrogate marker of type 2 cells, in 10 healthy anti-hepatitis C virus (HCV)-seropositive blood donors without viremia (group A) and in 15 patients with hepatitis C (group B). Intracytoplasmic IFN-gamma, IL-2, IL-4, and IL-10 were determined by triple-color flow cytometry in the CD3+ and CD3+/CD30+ lymphocyte subsets after stimulation of PBMC with rHCV core protein and five core-derived peptides corresponding to the four immunodominant Th epitopes C.T1 to C.T4. In group A, more type 1 cytokines were induced by the rHCV core protein and all immunodominant core peptides (p < 0.05), whereas IL-10-producing T cells were found more frequently in group B. Induction of CD30+ T cells was found almost exclusively in group B (p < 0.01). The difference in cytokine responses was due to the CD3+/CD30- T cell subset and not the CD3+/CD30+ subset, which predominantly produced both IL-10 and IFN-gamma, but only small amounts of IL-2 and IL-4. We conclude that immunodominant HCV core peptides induce preferentially type 1 cytokines in healthy anti-HCV-positive blood donors and CD30 expression in patients with chronic hepatitis C. However, in both groups, CD30+ T lymphocytes produce an intermediate Th0-like cytokine profile. Thus, chronicity in HCV infection may reflect a lack of type 1 cytokine production.

Adult↗
PubMed1997

IgG-antibodies to CNS proteins in patients with multiple sclerosis.

The CSF and sera of 185 patients with multiple sclerosis (MS), 130 patients with other inflammatory diseases of the CNS (OID) and 50 patients with spinal disc syndrome (controls) were investigated for IgG-antibodies to CNS proteins by SDS-PAGE and immunoblotting and by isoelectric focusing combined with affinity blotting. IgG-antibodies to CNS proteins in serum (immunoblotting) were detected in 18 patients with MS (10%), in 29 patients with OID (22%) and in four controls (8%). Intrathecal synthesis of IgG-antibodies to CNS proteins was demonstrated in 11 patients with MS (6%), in 37 patients with OID (28%) and in none of the controls. In 4/11 patients with MS intrathecally produced antibodies were shown to be specific for glial fibrillary acidic protein (GFAP). Of patients with MS, 180 displayed oligoclonal IgG-bands in the CSF. Specificity of these bands for CNS proteins was demonstrated only in 2/180 specimens (1%). These findings indicate, that in most patients with MS oligoclonal IgG-bands in the CSF do not contain relevant amounts of antibodies to CNS proteins.

Enzyme-Linked Immunosorbent Assay↗
PubMed1997

[Follow-up and prognosis of early summer meningoencephalitis].

Sixty-three patients with tick-borne encephalitis were studied for sequelae up to 5 years after the acute illness (median: 12 months, range: 1-44 months). Patients were examined clinically, by neuropsychological testing and by electroencephalography. The clinical presentation during the acute stage was as follows: Meningitis (M,n = 12), Meningoencephalitis (Me,n = 27), Meningoencephalomyelitis (My,n = 15), and Meningoencephaloradiculitis (R,n = 9). A total of 59 patients reported a neurasthenic syndrome after discharge, which correlated with the severity of the acute illness. Twenty patients were not able to work because of reduced stress tolerance, fatigue or an elevated emotional sensitivity, which lasted for 3 months at most. In some patients hypacusis (n = 7), severe dysarthria and dysphagia (n = 4) remained essentially unimproved for years following the acute illness. While in 8/9 patients with radiculitis paresis of the extremities improved well over months to years, improvement was quite limited in all patients with myelitis. In 41/55 patients, investigations by electroencephalography revealed normal findings even within months after acute illness. Persistent cognitive deficits were present only in 7/11 patients with a severe course of disease.

Adolescent↗
PubMed1997

[Vasculitis course of neuroborreliosis with thalamic infarct].

A-20-year-old man without vascular risk factors presented with paraesthesia of the left side of the body with acute onset. Cerebral magnetic resonance imaging showed an infarction in the right thalamus. Intra-arterial digital subtraction angiography revealed stenosis of the right thalamic vessels. Recent infection by Borrelia burgdorferi was demonstrated by typical findings in the cerebrospinal fluid: lymphocytic pleocytosis and intrathecal synthesis of borrelial-specific antibodies. The diagnosis of a borrelial-induced vasculitis with secondary thalamic infarction was made from these findings. After antibiotic treatment with cefrtriaxone, the patient was discharged without residual complaints.

Adult↗
PubMed1997

Prevalence of antibodies to Borrelia burgdorferi and tick-borne encephalitis virus in an endemic region in southern Germany.

With the intention to evaluate the frequency of asymptomatic infections with TBE virus and B. burgdorferi clinical data and serum specimens were collected from 393 individuals living in an area endemic for both agents (Freiburg, southern Germany). Sera were examined by ELISA. Borderline and positive results were checked by immunoblotting. Only specific antibodies detected by immunoblotting (B. burgdorferi: 22 kDa, 31 kDa, 34 kDa, 39 kDa, 83 kDa; TBE: glycoprotein E) were assessed as positive findings. Specific antibodies to B. burgdorferi were detected in 17/105 individuals with possible symptoms of borreliosis (16%) and in 36/288 individuals without current or previous symptoms of borreliosis (12.5%). Antibody to TBE virus was demonstrated in 34/361 individuals (9.4%) without clinical symptoms of TBE or vaccination against TBE. Thirty individuals had been immunised against TBE (10.6%) and two had clinical TBE one year ago. Antibodies against both agents were detected only in 1.5% of all subjects. Considering the low seroprevalence, antibody screening is not recommended prior to TBE vaccination.

Antibodies, Bacterial↗
PubMed1997

Production of a single-chain fragment of the murine anti-idiotypic antibody ACA125 as phage-displayed and soluble antibody by recombinant phage antibody technique.

The F(ab')2 fragment of the murine monoclonal anti-idiotypic antibody ACA125 mimicking the tumor-associated antigen CA125 is used as a vaccine for the induction of an anti-tumoral immunity in patients with ovarian carcinoma. We tried to generate a single-chain fragment (ScFv) composed of ACA125 heavy- and light-chain variable domains connected by a polypeptide linker as an alternative to the corresponding F(ab')2 fragment. Heavy- and light-chain genes of antibody-producing mouse hybridoma cell line were amplified separately and assembled into a ScFv gene with linker DNA by the polymerase chain reaction (PCR). The ScFv gene was ligated into the phagemid vector pCANTAB5E, which allows the production of both phage-displayed and soluble ScFv. Transformed Escherichia coli TG1 cells were infected with M13K07 helper phage to yield recombinant phage, which display ScFv fragments as a g3p fusion protein on the surface of the filamentous phage M13. Recombinant phages could be selected by binding to the idiotypic antibody OC125 after one round of panning and directly used to reinfect E. coli TG1 cells. The E. coli nonsuppressor strain HB2151 was infected with an antigen-positive phage clone, previously screened by enzyme-linked immunosorbent assay (ELISA), to express soluble ScFv fragments. Functional soluble ScFv binding to the idiotypic antibody OC125 F(ab')2 could be detected in the bacterial periplasm by Western blot and ELISA. The variable heavy- and light-chain genes of the ACA125 ScFv fragment were further sequenced and compared with known antibody sequences.

Amino Acid Sequence↗
PubMed1996

Fructose-1,6-bisphosphatase. Primary structure of the rabbit liver enzyme. 'Intermediate' variability of an oligomeric protein.

The primary structure of rabbit liver fructose-1,6-bisphosphatase was determined by peptide analysis of digests with different proteases. The results establish the primary structure, complete data bank entries, and show that this enzyme variant is indeed homologous with other liver fructose-1,6-bisphosphatases. Residue differences with the enzymes from other mammals are 9-15%, with those from plants and yeasts about 50%, and with those from characterized prokaryotes up to 70%, showing an enzyme variability intermediate between those of 'variable' and 'constant' oligomeric dehydrogenases. Structural relationships, conformations and catalytic mechanisms are consistent within the family of fructose-1,6-bisphosphatases, and the rabbit protein is a typical rather than an aberrant form of the enzyme.

Adenosine Monophosphate↗
PubMed1996

T- and B-cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti-hepatitis C virus--positive blood donors without viremia.

As the host's immune response may determine the course of hepatitis C virus (HCV) infection, we studied the humoral and cellular immune responses to HCV-related antigens in subjects with different outcomes of HCV infection. Lymphoproliferative responses and circulating antibodies to a panel of HCV core- and E1-related 25-mer peptides were examined in 10 healthy anti-HCV-seropositive blood donors (group A) and in 29 patients with chronic hepatitis C (group B). In addition, cellular recognition of recombinant HCV proteins (core, NS3, NS4A, NS5A, NS5B) were investigated. In group A, stronger T-cell responses were detected against both HCV proteins (core, P = .03; NS4, P = .005; NS5B, P = .03) and peptides. Proliferation was induced by the same peptides in each group, defining at least five distinctive epitopes within core (amino acids [aa] of 20-44, aa 39-63, aa 79-103, aa 118-152 and aa 148-172) and three regions within E1(aa 198-252, aa 308-372, and aa 368-392). Subjects with strong T-cell responses had low or no detectable levels of peptide-specific antibodies, and vice versa. In particular, T-cell responses were more common in group A; B-cell responses were more common in group B. From our data, we conclude that a benign course of HCV infection may be the consequence of the effective activation of T-helper lymphocytes.

Adolescent↗
PubMed1996

Human gene therapy in gastrointestinal diseases: in vivo and in vitro approaches.

The first clinical trial in human gene therapy began in 1989 with the successful introduction of marker genes into peripheral blood cells as tumor-infiltrating lymphocytes (TIL) in order to investigate the biological behavior of manipulated cells in humans. In further studies, it was possible to ameliorate clinical genetic diseases based on only one single genetic defect such as adenosine deaminase deficiency (ADA) by repeated infusion of manipulated peripheral blood cells. Meanwhile, a multitude of clinical gene transfer studies were initiated. Three main strategies have thus far been applied in human cancer gene therapy: (1) Reinforcement of the body's immune response by gene transfer into immunological cells; (2) reinforcement of the immune response by manipulating tumor cells; and (3) transfer of drug-sensitive genes into tumor cells with subsequent drug treatment. The first clinical trial in gene therapy for gastrointestinal diseases was performed in 1992 with the introduction of the low-density protein receptor gene (LDL) into liver tissue. Human cancer gene therapy of gastrointestinal diseases is still only in the initial phase of research.

Adenosine Deaminase↗
PubMed1996

[Evaluation of a stay and care center for drug addicts in Lucerne].

UNLABELLED: Between April 1992 and March 1994 a low threshold centre named "Aufenthalts- und Betreuungsraum für Drogenabhängige (ABfD)" ("Common Care Room for Drug Addicts") was run in the city of Lucerne which intended to help drug addicts to live and survive in terms of harm and risk reduction. The evaluation of the ABfD was conducted by the Institute for Social and Preventive Medicine on behalf of the Federal Office of Health. Combining qualitative and quantitative research methods its structure was evaluated regarding the realization of its own objectives. THE RESULTS: the ABfD was frequented beyond expectation by an average of about 65 male and female drug addicts per evening. All of its facilities were used and appreciated. The clientele of the ABfD was characterized by a great diversity of sociodemographic factors such as age, sex and income as well as housing conditions. The majority were residents of the city (approx. 54%) and the canton of Lucerne (approx. 28%). In general, the ABfD had a positive effect on the physical condition of its user insofar as the distribution of sterile injecting material enabled them to behave more risk consciously. Also, it gave many drug addicts something like a home and the opportunity to experience an atmosphere of solidarity. In spite of isolated criticism the ABfD generally enjoyed great esteem. The evaluation has shown that there is a need for a care center for drug addicts such as the ABfD, that it had been widely made use of, realized many of its objectives and it had no attractive effect on other regions. The researchers concluded by recommending the establishment of an analogous institution within a sensible period of time since with the closing of the ABfD in the Lucerne area the help to live and survive, an important pillar of the drug policy was no longer warranted for.

Adult↗
PubMed1996

HIV colonizing peripheral blood monocytes follows lymphocytic isolates in shifting from NSI to SI genotype.

Non-syncytium inducing (NSI) and syncytium inducing (SI) variants of human immunodeficiency virus (HIV) isolated from peripheral blood mononuclear cells (PBMC) could be definitely typed by sequence analysis of the env-gene V3 region. It was thus possible to compare the genotypes of viral variants isolated from PBMC and accompanying monocyte cultures and those derived directly from the patients' blood cells prior to cultivation. Within the investigated group of patients it was shown that HIV variants colonizing monocytes displayed a similar shift from NSI to SI as observed previously for PBMC, i.e. lymphocyte derived isolates. Lymphocytic SI variants could be isolated from the blood of patients, while simultaneously the predominant provirus in both blood and monocytic isolate was NSI. Consequently, we observed a delayed switch in the predominant provirus genotype found in blood which was associated with a synchronous change in the genotype of the corresponding monocytic isolate. The results show that monocytes/macrophages can be colonized by heterogeneous HIV variants in vivo and can therefore also function as carriers for the spread of highly virulent SI variants into the tissues.

Amino Acid Sequence↗
PubMed1996

Geographic distribution and origin of CFTR mutations in Germany.

The geographic distribution and origin of CFTR mutations in Germany was evaluated in 658 three-generation families with cystic fibrosis (CF). Fifty different mutations were detected on 1305 parental CF chromosomes from 22 European countries and overseas. The major mutation. delta F508 was identified on 71.5% of all CF chromosomes, followed by R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%). According to the grandparents' birthplace, 74% of CF chromosomes had their origin in Germany; the delta F508 percentage was 77%, 75%, 70% and 62% in northern, southern, western and eastern Germany, respectively. Ten or more mutant alleles in the investigated CF gene pool originated from Austria, the Czech Republic, Poland, Russia, Turkey and the Ukraine. This widespread geographic origin of CFTR mutations in today's Germany reflects the many demographic changes and migrations in Central Europe during the 20th century.

Cystic Fibrosis↗
PubMed1996

Elucidation of an HIV-1 transmission from mother to child in west Africa by sequence analysis.

A pregnant woman living in Germany went to Ghana for several months, where she received 4 blood transfusions. Her newborn child also received one blood transfusion in West Africa. After return to Germany, HIV-1 infection was detected in both of them. Serotyping with V3 peptides revealed that the sera reacted only poorly with the subtype B-specific antigens. To investigate whether the child had been infected by vertical or parenteral transmission, we amplified different proviral HIV-1 gene segments from samples obtained 1-3 years after infection. Sequence analysis of the hypervariable regions V1 and V2 of the proviral env gene was misleading, since the viral population of the mother was highly heterogeneous, whereas only one predominant viral variant was found in the child. In contrast, sequences of the gag p17 gene and the regulatory genes nef and vif were homogeneous and revealed a very high homology, suggesting that the child had been infected by the mother. This was confirmed by phylogenetic tree analysis showing that sequences of mother and child clustered together and that both were infected by HIV-1 subtype A which is common in West Africa. The results suggest that sequence analysis of the hypervariable regions V1 and V2 alone can lead to unclear results, especially if not single genomes are analysed but a mixture of quasi-species. It is recommended that investigations into HIV transmission should be based on sequence analysis of several HIV genes.

Africa, Western↗