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Biomedical subjects

R Kaiser

Publications and source records attributed to R Kaiser.

At least 73 records · Page 4Linked to original sources

Multiple scattering of light by atoms in the weak localization regime

Coherent backscattering is a multiple scattering interference effect which enhances the diffuse reflection off a disordered sample in the backward direction. Classically, the enhanced intensity is twice the average background under well chosen experimental conditions. We show how the quantum internal structure of atomic scatterers leads to a significantly smaller enhancement. Theoretical results for double scattering in the weak localization regime are presented which confirm recent experimental observations.

Journal Article↗

Demonstration of anti-HuD specific oligoclonal bands in the cerebrospinal fluid from patients with paraneoplastic neurological syndromes. Qualitative evidence of anti-HuD specific IgG-synthesis in the central nervous system.

The presence of HuD-specific oligoclonal IgG bands in the CSF was investigated in five patients with paraneoplastic neurological syndromes. All patients revealed intrathecal synthesis of HuD specific antibodies in the CSF, as estimated from elevated antibody indices (>1.5) in an IgG-ELISA using recombinant HuD-protein as antigen. Isoelectrofocussing combined with affinity blotting showed reactivity of IgG bands with recombinant HuD antigen in all CSF samples. These data support the idea that HuD specific antibodies in the CSF are produced mainly by B-cell clones in the central nervous system. These findings support the hypothesis of autoimmunity in the pathogenesis of anti-Hu associated paraneoplastic neurological syndromes.

Aged↗

[Epidemiology and progress of early summer meningoencephalitis in Baden-Württemberg between 1994 and 1999. A prospective study of 731 patients].

BACKGROUND AND OBJECTIVE: Tick-borne encephalitis (TBE) may develop into a serious disease leading to invalidism in a considerable proportion of patients. Detailed clinical and epidemiological data about the risks of TBE in Baden-Württemberg have been missing. A prospective study was started in 1994 to investigate the areas of risk in this part of Germany and to describe the clinical course and prognosis of TBE. PATIENTS AND METHODS: Doctors at all departments of Internal Medicine, Neurology and Paediatrics, at diagnostic laboratories and the departments of public health were asked to participate in this study. Data were recorded by means of a questionnaire. RESULTS: Between 1994 and 1999, 771 patients with TBE were recorded. Detailed clinical and epidemiological data were available for 731 patients. In 88% of the patients infection took place during leisure time activity, two thirds of infections occurring between June and August. The median incubation period was 8 days with a range of 4-28 days. 71% of the patients reported a prodromal stage with flu-like symptoms. TBE manifested as isolated meningitis in 47%, as meningoencephalitis in 42% and as meningoencephalomyelitis in 11%. With increasing age the number with a serious course of disease also increased. The most frequent symptoms were impairment of consciousness, ataxia and pareses of the limbs. In the children, the course of disease and prognosis was much better than in adults. Of 230 patients who were re-examined between 1 and 5 years after the acute illness 23% suffered from persisting moderate or severe symptoms. The death rate was about 1.4%. CONCLUSION: In Baden-Württemberg, tick bites are associated with a high risk of tick-borne encephalitis and severe neurological complications. Therefore, active immunization is recommended for all persons exposing themselves to ticks. Persisting complications after TBE are by far more common than serious complications after active immunization.

Adolescent↗

Public-health impact of outdoor and traffic-related air pollution: a European assessment.

BACKGROUND: Air pollution contributes to mortality and morbidity. We estimated the impact of outdoor (total) and traffic-related air pollution on public health in Austria, France, and Switzerland. Attributable cases of morbidity and mortality were estimated. METHODS: Epidemiology-based exposure-response functions for a 10 microg/m3 increase in particulate matter (PM10) were used to quantify the effects of air pollution. Cases attributable to air pollution were estimated for mortality (adults > or = 30 years), respiratory and cardiovascular hospital admissions (all ages), incidence of chronic bronchitis (adults > or = 25 years), bronchitis episodes in children (< 15 years), restricted activity days (adults > or = 20 years), and asthma attacks in adults and children. Population exposure (PM10) was modelled for each km2. The traffic-related fraction was estimated based on PM10 emission inventories. FINDINGS: Air pollution caused 6% of total mortality or more than 40,000 attributable cases per year. About half of all mortality caused by air pollution was attributed to motorised traffic, accounting also for: more than 25,000 new cases of chronic bronchitis (adults); more than 290,000 episodes of bronchitis (children); more than 0.5 million asthma attacks; and more than 16 million person-days of restricted activities. INTERPRETATION: This assessment estimates the public-health impacts of current patterns of air pollution. Although individual health risks of air pollution are relatively small, the public-health consequences are considerable. Traffic-related air pollution remains a key target for public-health action in Europe. Our results, which have also been used for economic valuation, should guide decisions on the assessment of environmental health-policy options.

Adolescent↗

Comparison between a nucleic acid sequence-based amplification and branched DNA test for quantifying HIV RNA load in blood plasma.

HIV RNA was quantified in blood plasma from 209 patients and in control specimen comparing the NucliSens HIV-1 QT test (Organon Teknika), which is based on the nucleic acid sequence amplification procedure, and the Quantiplex 3.0 test (Bayer), which uses hybridization signal enhancement by branched DNA (bDNA) probes. A highly significant correlation (P=0.01) was found between the two methods with 88% of the samples showing similar results. In cases of discrepant findings, higher virus load was observed with either test (14xNASBA>bDNA; 12xbNDA>NASBA). Differences could neither be related to clinical features nor to divergent virus subtypes. Standard preparations containing 35000 and 222000 copies were quantified with intra-assay coefficients of variation of <20% using both methods. A preparation of 192 copies was measured with lower precision by both tests, yet was detected more reliably by the bDNA method.

Blotting, Western↗

Dopamine D4 receptor 48-bp repeat polymorphism: no association with response to antipsychotic treatment, but association with catatonic schizophrenia.

The dopamine D4 receptor (DRD4) may play a role in the pathogenesis of neuropsychiatric disease and in the action of dopaminergic drugs. The 48-bp repeat polymorphism (48-bp VNTR) coding for a 16-amino acid segment in the third cytoplasmatic loop of the DRD4 was studied as a predictor of the therapeutic response to antipsychotics and as susceptibility factor for schizophrenia. We included 638 in-patients with acute schizophrenic, schizoaffective (mainly schizophrenic), and other nonaffective psychoses, as well as two reference groups: one with 278 in-patients with non-psychiatric diseases, and one with 474 healthy volunteers. Catatonic patients (DSM-IV 295.2) more frequently carried the DRD4 D4.2 and D4.3 allele than did all other schizophrenic cases (P < 0.001; OR: 2.7; CI: 1.5-4.9) and controls (P < 0.004; OR: 2.3; CI: 1.3-4.2). We found no significant difference in the DRD4 allele or in genotype frequencies in our comparison of all schizophrenic patients and controls. The subgroups with affected family members, and the subgroups with early or late onset of disease, also did not differ from the controls in DRD4 allele frequencies. The 48-bp VNTR was not a predictor for therapeutic outcome measured by the positive and negative symptoms scale. A total of 1390 subjects showed between 1 and 10 repeats (D4. 1 and D4.10), with 25 different genotypes. These data exclude a major role of DRD4 48-bp VNTR in response to antipsychotic therapy and as susceptibility factor for schizophrenia, but catatonic schizophrenia may be associated with the D4.2 and D4.3 alleles.

Adolescent↗

Anisotropy and multiple scattering in thick mammalian tissues.

A dual-channel Mach-Zehnder interferometer using heterodyne detection allowed us to measure simultaneously parallel and perpendicular polarization components through various mammalian tissues at a wavelength of lambda = 633 nm. By contrast with liver tissue, squeletic muscles of a few millimeters thickness exhibit strong anisotropic properties that change the direction of the linear polarization of the light. This rotation of the initial plane of polarization is to be distinguished from the depolarization that is due to the multiple light scattering that goes along with large temporal fluctuations. Complementary photos under linearly polarized light illustrate the behavior difference between liver (isotropic medium) and muscle (anisotropic medium).

Animals↗

Failure of double protease inhibitor therapy as a salvage therapy for HIV-infected patients resistant to conventional triple therapy.

A therapeutic dilemma arises once HIV-infected patients develop a break-through of HIV-replication under potent antiretroviral therapy. Therefore, we studied whether patients (n = 12) who failed double nucleoside reverse transcriptase (NRTI) plus indinavir or ritonavir triple therapy can be rescued when therapy is switched to double protease inhibitor (PI) treatment (nelfinavir and hard gel saquinavir) and stavudine. With the rescue regimen HIV-RNA levels initially dropped from 148,571 +/- 45,258 copies/ml to 9,310 +/- 6, 965 copies/ml at week 4 (p = 0.0117). However, virus load subsequently increased to almost baseline levels (131,230 +/- 37,743 copies/ml) at week 12. Likewise, CD4-cell counts could only be stabilized initially (baseline 267 +/- 51; week 4 296 +/- 65 cells/microl), but gradually declined thereafter (216 +/- 34 cells/microl week 12). Before therapy was switched, the viral protease gene from 5 analyzed patients showed 3-5 amino acid substitutions. Moreover, 4 of these patients had one amino acid substitution associated with resistance to nelfinavir. Our data suggest that HIV-infected patients resistant to indinavir or ritonavir and double NRTI combination therapy respond to double PI nelfinavir/saquinavir and D4T rescue therapy only initially but have no sustained benefit.

Anti-HIV Agents↗

Protection against parenteral HIV-1 infection by homozygous deletion in the C-C chemokine receptor 5 gene.

OBJECTIVES: To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1. DESIGN: The prevalence of the delta32 deletion within the CCR5 gene was determined in a cohort of 207 patients, who had received documented amounts of non-antibody-tested and non-inactivated clotting factor concentrate. METHODS: Chromosomal DNA of haemophiliacs was isolated from whole blood. A portion of the CCR5 gene spanning the delta32 deletion was amplified by PCR. The resulting DNA fragments were analysed by agarose gel electrophoresis. RESULTS: The rate of HIV-1 infection was correlated strongly with increasing amounts of inoculated clotting factor concentrate. None of the HIV-positive patients (n = 129) had the delta32/delta32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous delta32 deletion. CONCLUSIONS: The delta32/delta32 genotype was highly protective against HIV-1 infection, even in patients who had received millions of non-inactivated clotting factor units. As it is likely that in the early 1980s plasma pools were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 appears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infected haemophiliacs who have wild-type CCR5.

Base Sequence↗

Enhancement of cyanogen bromide cleavage yields for methionyl-serine and methionyl-threonine peptide bonds.

Cyanogen bromide (CNBr) is a common chemical used to hydrolyze peptide bonds C-terminal to methionine residues in peptides and proteins. In most cases, the efficiency of this bond cleavage is greater than 90% except in situations where a serine or threonine residue follows methionine in the amino acid sequence. We have explored the mechanism of the methionyl-serine and methionyl-threonine CNBr cleavage inefficiencies and have developed a simple methodology to more than double cleavage yields relative to standard literature conditions. This method entails increasing the concentration of water during the cleavage reaction either by reducing the formic acid concentration or by performing the cleavage in an acidic aqueous medium. This approach provides a more desirable methodology from the perspective of enhanced yields and greater ease of handling in cases of large-scale use.

Chromatography, High Pressure Liquid↗

Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution.

The three-dimensional structure of the R form of rabbit liver fructose 1,6-bisphosphatase (Fru-1,6-Pase; E.C. 3.1.3.11) has been determined by a combination of heavy-atom and molecular-replacement methods. A model, which includes 2394 protein atoms and 86 water molecules, has been refined at 2.3 A resolution to a crystallographic R factor of 0.177. The root-mean-square deviations of bond distances and angles from standard geometry are 0.012 A and 1.7 degrees, respectively. This structural result, in conjunction with recently redetermined amino-acid sequence data, unequivocally establishes that the rabbit liver enzyme is not an aberrant bisphosphatase as once believed, but is indeed homologous to other Fru-1,6-Pases. The root-mean-square deviation of the Calpha atoms in the rabbit liver structure from the homologous atoms in the pig kidney structure complexed with the product, fructose 6-phosphate, is 0.7 A. Fru-1,6-Pases are homotetramers, and the rabbit liver protein crystallizes in space group I222 with one monomer in the asymmetric unit. The structure contains a single endogenous Mg2+ ion coordinated by Glu97, Asp118, Asp121 and Glu280 at the site designated metal site 1 in pig kidney Fru-1,6-Pase R-form complexes. In addition, two sulfate ions, which are found at the positions normally occupied by the 6-phosphate group of the substrate, as well as the phosphate of the allosteric inhibitor AMP appear to provide stability. Met177, which has hydrophobic contacts with the adenine moiety of AMP in pig kidney T-form complexes, is replaced by glycine. Binding of a non-hydrolyzable substrate analog, beta-methyl-fructose 1,6-bisphosphate, at the catalytic site is also examined.

Allosteric Site↗

[Paraneoplastic neurologic syndromes. Diagnostic and pathogenetic significance of autoantibodies].

Paraneoplastic neurologic syndromes (PNS) are rare disorders of the nervous system that cannot be ascribed to metastases or to destruction of vital systemic organs by the tumor or its treatment. Most frequently, PNS occur in association with small-cell lung, breast or ovarian carcinomas. The most frequent PNS is Lambert-Eaton myasthenic syndrome, which at the same time has the highest predictive value concerning an underlying carcinoma. PNS have been classified mostly under anatomical aspects but now are increasingly categorized according to specific antibodies. In certain neurologic syndromes (sensible and autonomic neuropathy, cerebellitis, limbic encephalitis, Opsoclonus-Myoclonus syndrome, Stiff-man syndrome, neuromyotonia, subacute amaurosis) specific autoantibodies are highly predictive for a neoplasm. Pathogenic relevance of these autoantibodies has been demonstrated only for antibodies against (1) voltage gated calcium channels (VGCC) in Lambert-Eaton myasthenic syndrome, (2) voltage gated potassium channels (VGKC) in neuromyotonia, and (3) recoverin in cancer associated retinopathy. The present article deals with the neurological symptoms of PNS, associated tumors, and the relevance of specific antibodies for the diagnosis and pathogenesis of PNS.

Animals↗

[Biological hallucinogens. New patterns of substance abuse in young addicts?].

Among young patients with multiple substance abuse, a high level of abuse of natural products was noticed. In a rehabilitation clinic for young addicts 180 patients filled out a questionnaire regarding drugs they regularly consumed. It was discovered that the patients consumed high levels of Psilocybe, Amanita and Datura. The natural drugs of the 70's, Ayahuasco and Cactus, are now rarely seen. The toxicological basis of the frequently used biological drugs is discussed. The results imply that a specific exploration of patients with multiple substance abuse in regard to the use of biological drugs is necessary.

Adolescent↗

Decreased frequency of HCV core-specific peripheral blood mononuclear cells with type 1 cytokine secretion in chronic hepatitis C.

BACKGROUND/AIM: Since the outcome of hepatitis C infection appears to be correlated with the immune response to the HCV core protein, the aim of this study was to investigate the T cell response to hepatitis C virus core and core-derived antigens. METHODS: As this response may be regulated importantly by differential secretion of cytokines, we determined the number of peripheral blood mononuclear cells (PBMC) that secreted IL-2, IL-4, IL-10, and IFN-gamma in response to a recombinant HCV core protein and a panel of 19 core-derived peptides, using the ELI-Spot-technique. Two groups of patients were studied: group A: 11 patients with previously self-limited HCV infection; group B: 12 patients with chronic hepatitis C. RESULTS: In group B significantly less IFN-gamma spot forming cells (SFC) could be detected, both after stimulation with the core protein (0.083+/-0.083 SFC vs. 1.3+/-0.4 SFC/10(5) PBMC; p = 0.005 and with the core-derived peptides (1.3+/-0.5 vs. 4.4+/-1.1 SFC SFC/10(5) PBMC; p = 0.007). By analyzing the cytokine response to each single peptide, we found IFN-gamma responses to peptides aa 39-63 and aa 148-172 in group A but not in group B (p<0.03). In group B also, fewer IL-2 secreting cells were found after peptide stimulation (p = 0.04). Whereas subjects of group B showed IL-10-specific responses to HCV peptides more frequently than patients with self-limiting hepatitis C (p = 0.03), the number of IL-4-producing cells was not different between the two groups. CONCLUSIONS: The data suggest that patients with persistent viremia and chronic liver disease (group B) have less PBMC showing type 1 cytokine (IL-2, IFN-gamma) responses to HCV core protein than patients with self-limited HCV infection (group A).

Chronic Disease↗

Increased frequency of the HLA-DR15 (B1*15011) allele in German patients with self-limited hepatitis C virus infection.

BACKGROUND: A genetically determined resistance or susceptibility to chronic hepatitis C virus infection (HCV) may make an important contribution to the course of liver disease and may be linked to the human major histocompatibility complex. DESIGN: Twenty-one subjects with self-limited HCV infection as assessed by the presence of HCV antibodies, absence of HCV-RNA and normal levels of aminotransferases for 2 years were identified from a large pool of blood donors. The frequency of HLA serotypes of these individuals was compared with 49 consecutive patients with chronic hepatitis C. RESULTS: We detected a significantly higher prevalence of HLA-DR15 in patients with self-limited HCV infection than in patients with chronic hepatitis C (10/21 vs. 6/49; relative risk 6.5; P = 0.02; corrected for multiple comparisons). To confirm HLA assignments by serotyping we also performed sequencing of HLA-DR types in the 27 patients (9 with self-limited infection, 18 with chronic hepatitis C) who had been enrolled during 1995-96. This analysis confirmed the predominance of HLA-DR15 (HLA-DRB1*15011) in self-limited HCV infection (4/9 vs. 1/18; relative risk 13.6; P = 0.03). CONCLUSIONS: Our data suggest that HLA-DR15 (B1*15011) might constitute an important genetic factor for the elimination of the hepatitis C virus in Germany.

Adolescent↗

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.

BACKGROUND: Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. METHODS: Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (+/- SD) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 +/- 5 and 25 +/- 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 +/- 1037 (887) and 1402 +/- 1183 (1430) ml/24 hr and 6.4 +/- 5.9 (4.3) and 8.7 +/- 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 microgram/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate. RESULTS: During the treatment period, which averaged 10.7 +/- 4.1 and 10.6 +/- 4.5 days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo-treated patients died during the 28 days after the onset of treatment. CONCLUSIONS: rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.

Acute Kidney Injury↗