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Biomedical subjects

H Weiss

Publications and source records attributed to H Weiss.

At least 91 records · Page 5Linked to original sources

Gastroscopic band removal after intragastric migration of adjustable gastric band: a new minimal invasive technique.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is the most used procedure for bariatric surgery in Europe. Although a low complication rate is reported, band migration within the first 2 years after LAGB is still observed in nearly 5% of cases, requiring operative band removal. To avoid increased risk of complications due to laparotomy, we propose a minimally invasive technique for this purpose. METHODS: We performed this operation in five patients who suffered from band migration after LAGB (1.9% in our series of 211 patients, one patient was operated elsewhere). The described method consists of gastroscopic band and tube removal, combined with removal of the port under local anesthesia. RESULTS: The described procedure was developed in the endoscopy unit without additional equipment. The mean operating-time ranged from 65 to 180 minutes (mean 135 minutes). No perioperative complication were observed. In-patient treatment was necessary for 4 days. CONCLUSIONS: A novel technique for minimally invasive band removal after adjustable gastric band migration is described, offering the patient a low-risk procedure and a better chance for further laparoscopic approaches.

Adult↗

An improved nonfluorescent detection system for in situ hybridization in plants.

Molecular cytogenetics, particularly the localization of DNA sequences by in situ hybridization, has increased our understanding about the genomic structure of plants and animals. We demonstrate here the application of an improved nonfluorescent in situ hybridization system detection (DAKO GenPoint system) to plant chromosomes. Using this system, highly repetitive 18S-25S rRNA genes were mapped on Vicia faba chromosomes (2n = 12). The modified method of this horseradish peroxidase based enzymatic detection system gave satisfactory results that are comparable to fluorescent signal detection.

Chromosomes↗

A reductase/isomerase subunit of mitochondrial NADH:ubiquinone oxidoreductase (complex I) carries an NADPH and is involved in the biogenesis of the complex.

Respiratory chains of bacteria and mitochondria contain closely related forms of the proton-pumping NADH:ubiquinone oxidoreductase, or complex I. The bacterial complex I consists of 14 subunits, whereas the mitochondrial complex contains some 25 extra subunits in addition to the homologues of the bacterial subunits. One of these extra subunits with a molecular mass of 40 kDa belongs to a heterogeneous family of reductases/isomerases with a conserved nucleotide binding site. We deleted this subunit in Neurospora crassa by gene disruption. In the mutant nuo 40, a complex I lacking the 40 kDa subunit is assembled. The mutant complex I does not contain tightly bound NADPH present in wild-type complex I. This NADPH cofactor is not connected to the respiratory electron pathway of complex I. The mutant complex has normal NADH dehydrogenase activity and contains the redox groups known for wild-type complex I, one flavin mononucleotide and four iron-sulfur clusters detectable by electron paramagnetic resonance spectroscopy. In the mutant complex these groups are all readily reduced by NADH. However, the mutant complex is not capable of reducing ubiquinone. A recently described redox group identified in wild-type complex I by UV-visible spectroscopy is not detectable in the mutant complex. We propose that the reductase/isomerase subunit with its NADPH cofactor takes part in the biosynthesis of this new redox group.

Electron Spin Resonance Spectroscopy↗

Androgenic regulation of growth factor and growth factor receptor expression in the CWR22 model of prostatic adenocarcinoma.

The effects of androgen manipulation on epidermal growth factor (EGF) receptor, p185erbB-2 and transforming growth factor-alpha (TGF-alpha) levels were examined in prostatic adenocarcinoma. Male nude mice were inoculated with the CWR22 androgen-dependent human prostatic tumor or an androgen-independent (CWR22R) derivative. Mice with CWR22 tumors were castrated and subsequently killed at 3, 7, 21, 28 or 42 days post-castration. Other CWR22-bearing mice received s.c. testosterone pellets at 21 days post-castration and were killed 7 days later. EGF receptor, p185erbB-2 and TGF-alpha levels were examined by immuno-histochemistry. Strong EGF receptor and p185erbB-2 immunostaining was detected in CWR22 tumors from intact controls. EGF receptor immunostaining decreased by 65% to 70% at 21 to 42 days post-castration. Testosterone treatment at 21 to 28 days post-castration resulted in a 2-fold increase in EGF receptor immunostaining. p185erbB-2 immunostaining within CWR22 tumors did not decrease following castration and, in fact, was slightly increased at 7 days post-castration. The effects of castration on EGF receptor and p185erbB-2 levels were confirmed by Western blot analysis. Fewer than 10% of CWR22 tumor cells demonstrated strong TGF-alpha immunostaining, and androgen manipulation did not effect TGF-alpha immunostaining. In contrast, 30% of androgen-independent CWR22R tumor cells were strongly immunostained for TGF-alpha. Our findings indicate that EGF receptor levels, but not p185erbB-2 levels, are strongly dependent on testosterone in CWR22 tumors. The co-localization of TGF-alpha and the EGF receptor in CWR22R tumors suggests that these factors may constitute an autocrine pathway that regulates androgen-independent growth.

Adenocarcinoma↗

Supramolecular Structure of Precipitated Nanosize beta-Carotene Particles.

A combination of analytical methods and molecular modeling calculations has provided a detailed picture of the supramolecular and microscopic structure of precipitated lipophilic carotenoids. The nanoparticles have a core/shell structure (see schematic representation) in which the particle core (120 nm) consists of a variety of molecular aggregates of different sizes, and the shell (40 nm) consists of an adsorbed gelatin layer.

Journal Article↗

Reduction in the mean number of Plasmodium falciparum genotypes in Gambian children immunized with the malaria vaccine SPf66.

SPf66, a synthetic peptide Plasmodium falciparum vaccine, did not protect young Gambian children against clinical attacks of malaria. Nevertheless, Gambian children who had been vaccinated with SPf66 and who were parasitaemic at the end of the first malaria transmission season after vaccination had significantly fewer detectable P. falciparum genotypes than control children, as determined by polymerase chain reaction analysis of 3 polymorphic loci--the msp1 block 2 repeat region, the msp2 repeat region, and the R11 region of the glutamate-rich protein gene (glurp). Geometric mean numbers of genotypes were 1.66 vs. 1.87, 1.95 vs. 2.43, and 1.21 vs. 1.50 for msp1, msp2 and glurp, respectively (P = 0.31, P = 0.04 and P < 0.01). Differences between groups became a little more marked for msp1 and msp2 when children with symptomatic malaria were excluded. No significant difference was found between parasites obtained from SPf66-vaccinated or control children in the prevalences of amino acid alleles at positions 44 and 47 in the 11 amino acid sequence of the merozoite surface protein 1 molecule, which is present in SPf66. The reduction in the number of genotypes observed could not be explained by a difference in parasite densities between SPf66-vaccinated and control children, as geometric mean parasite densities were almost identical in the 2 groups. These observations suggest that SPf66 vaccine may have induced an immune response which reduced the incidence of new infections in immunized children or accelerated the rate of clearance of parasites of individual genotypes. However, no reduction in the prevalence or density of parasitaemia was recorded in SPf66-vaccinated children, suggesting the existence of some kind of density-dependent mechanism for controlling low levels of malaria parasitaemia.

Animals↗

Serological responses of Gambian children to immunization with the malaria vaccine SPf66.

Antibody responses to the malaria vaccine SPf66 and to its constituent peptides were measured over a period of 2 years in Gambian children who had been immunized with SPf66 or with a control vaccine (inactivated polio vaccine). Three hundred and six of 308 children (99%) who had received three doses of SPf66 vaccine had antibodies to SPf66 at a level above that found in European controls who had not been exposed to malaria. Responses to the constituent peptides derived from 35.1, 55.1 and 83.1-kDa proteins were found in 88%, 97% and 97% of children, respectively; 26% had an antibody response to the NANP repeat peptide of circumsporozoite protein which is also included in the SPf66 vaccine. A response to SPf66 was found in 22% of children who had received the control vaccine. Antibody responses to NANP, 35.1, 55.1 and 83.1-kDa peptide were found in 3%, 33%, 49% and 33% of these children. Overall, no significant correlation was found between the level of anti-SPf66 antibody at the beginning of the malaria transmission season following vaccination and the subsequent risk of malaria. However, further analysis showed that among the control children who had acquired antibodies to SPf66 as a result of natural exposure to malaria, those with high levels of anti-SPf66 were less at risk of malaria, perhaps reflecting their greater previous exposure and thus immunity. In contrast, among children who had received three doses of SPf66, those with high antibody levels were at greater risk of have malaria during the subsequent malaria transmission season.

Animals↗

Evaluation of biomarker modulation by fenretinide in prostate cancer patients.

An NCI-sponsored, phase II trial of N-(4-hydroxyphenyl)- retinamide (4-HPR) in patients with organ-confined prostate cancer in the period prior to radical prostatectomy was carried out. Thirty-seven men with the histologic diagnosis of prostate cancer planning to have radical prostatectomy entered the study after informed consent and were given 4-HPR (or matching placebo) as a single daily dose (two 100-mg capsules of 4-HPR or two capsules of placebo daily) for 3 weeks prior to surgery. Four men dropped out for unrelated reasons. Thirty-three men completed the study. At the time of surgery, repeat biopsies of the prostate were performed to study the effects of the drug on potential surrogate endpoint biomarkers (SEBs) of malignancy within the tissue. The panel of potential SEBs of malignancy include p53, cytomorphometric indices, ploidy, PNCA, erbB-2, erbB-3, EGF receptor, TGF-alpha tumor-associated glycoprotein-72, fatty acid synthetase and Lewis Y antigen. Twenty-three patients had matching pre- and posttherapy lesions and were considered informative. Results from the patients indicate significant differential expression of biomarkers in pretreatment specimens of uninvolved prostatic tissue (normal-appearing epithelia) prostatic intraepithelial neoplasia (PIN) and prostate cancer. The mean erbB-2 expression was 0.58 in uninvolved vs. 1.04 in PIN (p = 0.002); while the mean erbB-2 expression was 1.35 in prostate cancer (p = 0.0007, uninvolved vs. prostate cancer). A similar pattern of increased biomarker expression between uninvolved and PIN or prostate cancer tissues can be observed for EGF receptor (mean = 1.21, 1.87 and 1.76 for uninvolved, PIN and prostate cancer, respectively) and erbB-3 (mean = 0.81, 1.59 and 1.30 for uninvolved, PIN and prostate cancer, respectively). There were no statistically significant differences in biomarkers observed in the 4-HPR-treated patients when compared with placebo-treated control patients. There was a posttreatment up-regulation of biomarkers observed in both groups of patients. This observation is most likely explained by an effect due to the diagnostic sextant biopsy equally affecting both groups of patients. Results from this study do not demonstrate a chemoprevention effect of 4-HPR on tissue-based SEBs at the dose given.

Adenocarcinoma↗

Permanent anatomic closure of the ductus arteriosus in newborn baboons: the roles of postnatal constriction, hypoxia, and gestation.

Permanent closure of the ductus arteriosus requires loss of cells from the muscle media and development of neointimal mounds, composed in part of proliferating endothelial cells. We hypothesized that postnatal ductus constriction produces hypoxia of the inner vessel wall; we also hypothesized that hypoxia might lead to cell death and the production of vascular endothelial cell growth factor (VEGF), a hypoxia-inducible growth factor that stimulates endothelial proliferation. We mapped the distribution of hypoxia in newborn baboons and correlated it with the appearance of cell death (TUNEL technique), VEGF expression, and endothelial proliferation (proliferating cell nuclear antigen expression). In the full-term baboon (n=10), the ductus was functionally closed on Doppler examination by 24 h after delivery. Regions of the ductus where the lumen was most constricted were associated with moderate/intense hypoxia; VEGF expression was increased in the hypoxic muscle media, and luminal endothelial cells, adjacent to the hypoxic media, were proliferating. Cells in the most hypoxic regions of the ductus wall were undergoing DNA fragmentation. In contrast, regions of the ductus with mild degrees of hypoxia had no evidence of cell death, VEGF expression, or endothelial proliferation. Cell death and endothelial proliferation seemed to be limited to regions of the full-term ductus experiencing moderate/intense hypoxia. In the premature baboon (67% gestation) (n=24), only 29% closed their ductus by Doppler examination before d 6. None of the premature baboons, including those with a closed ductus by Doppler, had evidence of moderate/intense hypoxia; also, there was no evidence of cell death, VEGF expression, endothelial proliferation, or neointima formation by d 6. Therefore, the premature ductus is resistant to developing hypoxia, even when its lumen is constricted; this may make it susceptible to later reopening.

Animals↗

Redox components and structure of the respiratory NADH:ubiquinone oxidoreductase (complex I).

The proton-pumping NADH:ubiquinone oxidoreductase is the first complex in the respiratory chains of many purple bacteria and of mitochondria of most eucaryotes. The bacterial complex consists of 14 different subunits. The mitochondrial complex contains at least 29 additional proteins that do not directly participate in electron transfer and proton translocation. We analysed electron micrographs of isolated and negatively stained complex I particles from Escherichia coli and Neurospora crassa and obtained three-dimensional models of both complexes at medium resolution. Both have the same L-shaped overall structure with a peripheral arm protruding into the aqueous phase and a membrane arm extending into the membrane. The two arms of the bacterial complex are only slightly shorter than those of the mitochondrial complex although the protein mass of the former is only half of that of the latter. The presence of a novel redox group in the membrane arm of the complex is discussed. This group has been detected in the N. crassa complex by means of UV-visible spectroscopy. After reduction with an excess of NADH and reoxidation by the lactate dehydrogenase reaction, a reduced-minus-oxidized difference spectrum was obtained that cannot be attributed to the known cofactors flavin mononucleotide (FMN) and the FeS clusters N1, N2, N3 and N4. Due to its positive midpoint potential the novel group is believed to transfer electrons from the FeS clusters to ubiquinone. Its role in proton translocation is discussed.

Computer Simulation↗

Consistent structure between bacterial and mitochondrial NADH:ubiquinone oxidoreductase (complex I).

Respiratory chains of bacteria and mitochondria contain closely related forms of the proton-pumping NADH:ubiquinone oxidoreductase (complex I). In bacteria the complex has a molecular mass of approximately 530 kDa and consists of 14 different subunits. The homologues of these 14 subunits together with some 27 additional subunits make up the mitochondrial complex, adding up to a molecular mass of approximately 1 MDa. We calculated three-dimensional models at medium resolution of isolated and negatively stained complex I particles from Eschericha coli and Neurospora crassa by electron microscopy using the random conical tilt reconstruction technique. Both the bacterial and the mitochondrial complexes are L-shaped molecules with an intrinsic membrane arm extending into the lipid bilayer and a peripheral arm protruding from the membrane. It is discussed whether the consistent length of the arms of both complexes has an implication for their function. The additional protein mass of the mitochondrial complex is distributed along both arms, but especially around the junction between the two arms and around the membrane arm. It appears that the structural framework of procaryotic complex I is stabilized in eucaryotes by this additional mass. A discrete location of additional protein in the peripheral arm of the mitochondrial complex is interpreted as being the possible position of two subunits with a specialized role in the biosynthesis of a yet unknown cofactor of complex I.

Bacterial Proteins↗

Search for novel redox groups in mitochondrial NADH:ubiquinone oxidoreductase (complex I) by diode array UV/VIS spectroscopy.

The proton-translocating NADH:ubiquinone oxidoreductase of mitochondria (complex I) is a large L-shaped multisubunit complex. The peripheral matrix arm contains one FMN and a number of iron-sulfur (FeS) clusters and is involved in NADH oxidation and electron transfer to the membrane intrinsic arm. There, following a yet unknown mechanism, the redox-driven proton translocation and the ubiquinone reduction take place. Redox groups that would be able to link electron transfer with proton translocation have not been found so far in the membrane arm. We searched for such groups in complex I isolated from Neurospora crassa. Under anaerobic conditions, the preparation was analyzed in different redox states by means of UV/VIS and EPR spectroscopy. Absorption bands in the UV/VIS redox difference spectra were found which cannot be attributed to the FMN or the EPR detectable FeS clusters. The existence of two novel groups is postulated and their possible locations in the electron pathway and their roles in proton translocation are discussed.

Electron Spin Resonance Spectroscopy↗

[Follow-up of myasthenia gravis. Results of a longitudinal study of the significance of psychosocial predictors].

Forty-two patients suffering from myasthenia gravis were examined in a longitudinal study design. The aim of the study was to investigate possible psychosocial predictors for the course of the disease. At the time of the first examination (T1) the diagnosis myasthenia gravis had been established for no longer than 1 year. Two further examinations were done at 6 months (T2) and 18 months (T3) after T1. Methods consisted of a personality questionnaire (FPI), a coping questionnaire (FKV), an assessment of neurotic symptoms by interviewers (PSKB) and an assessment of the doctor-patient relationship by the attending physicians. Two different severity scores (Oosterhuis Index, Myasthenia Score) served as criteria for the course of the disease. There was no connection between the course of myasthenia gravis and neurotic symptoms like anxiety or depression and the quality of the doctor-patient relationship (both assessed at T1). Also demographic data were independent from the development of severity scores. The personality factor extraversion was associated with a positive course of the disease, aggressiveness and worrying about health with a negative one. Among the coping behaviors religiousness and looking for sense were associated with a favorable course but that was shown only regarding the Oosterhuis Index and not the Myasthenia Score. As several T1 personality factors were predictive for the severity scores at T3, these results may suggest a causal influence of personality factors on the severity of the illness. Whether or not this relationship is actually in operation, however, remains ellusive. Further studies using an experimental design are needed to strengthen this hypothesis.

Adaptation, Psychological↗

[Time requirements of medical and non-medical personnel for ultrasound studies].

To assess the time needed for ultrasound examinations for physicians and assistants we carried out a survey among members of the German Association of Ultrasound in Medicine (DEGUM) in hospitals and practices. The physician's examination time for the investigation of the upper abdomen and kidneys was 12.3 min with additional time for preparation (2.9 min), for work up (2.3 min) and written documentation (3.6 min), together 21.3 min. The examination times in practices (18.9 min) are shorter than in ultrasound labs in hospitals. Assistants in ultrasound laboratories need for organisation, upkeep of equipment, to filing the images in archives etc. medium 15.2 min per patient. Assistants with exclusive employment in the ultrasound laboratory need 17.6 min (4-57 min), whereas assistants employed in the ultrasound laboratory and other departments need 12.7 min (1.6-31 min). In internal practices the desired time is 7.9 min (3.5-20 min). Because of the different organisation in the ultrasound laboratories in several hospitals and in practices a comparison of times needed by assistant personnel (or, in many cases, by the physicians who perform such work themselves) is very difficult. The examination time really needed by physicians and the time for assistant personnel are shorter than presumed earlier, but are longer than estimated in the recent discussion about money saving in medicine.

Abdomen↗

Nonconvulsive status epilepticus in the critically ill elderly.

PURPOSE: To describe the electrographic and clinical features of nonconvulsive status epilepticus (NCSE) in the critically ill elderly and to identify potential predictors of outcome. METHODS: We prospectively identified 25 episodes of altered mentation and NCSE in 24 critically ill elderly patients associated with generalized, focal, or bihemispheric epileptiform EEG patterns. Patients with anoxic encephalopathy were excluded. RESULTS: Of 25 hospitalizations, 13 (52%) resulted in death, and 12 (48%) patients survived to discharge. Death was associated with the number of acute, life-threatening medical problems on presentation (survivors, 1.8; fatalities, 2.8; p = 0.013) and with generalized EEG pattern (p = 0.017). Higher doses or greater number of antiepileptic drugs (AEDs) did not improve outcome. Treatment with intravenous benzodiazepines was associated with increased risk of death (p = 0.033). Ten patients with advance directives were managed outside the intensive care unit (ICU). Mean hospitalization was 39 days in the ICU group and 22 for those with advance directives (p = 0.017). CONCLUSIONS: Severity of illness correlates with mortality in critically ill elderly patients with NCSE. Treatment with intravenous benzodiazepines may increase their risk of death. Aggressive ICU management may prolong hospitalization at considerable cost, without improving outcome. It is unclear whether NCSE affects outcome in the critically ill elderly or is merely a marker for severity of disease in predisposed patients. The benefits of aggressive therapy are unclear. Carefully controlled, prospective trials will be necessary to determine the best therapies for NCSE in the critically ill elderly and the appropriate role of the ICU in their management.

Aged↗

Modular evolution of the respiratory NADH:ubiquinone oxidoreductase and the origin of its modules.

The proton-pumping NADH:ubiquinone oxidoreductase is the foremost of the respiratory chain complexes providing the proton motive force required for the synthesis of ATP. The complex is found in purple bacteria and in the mitochondria of most eukaryotes. The bacterial complex consists of 14 different subunits while the mitochondrial complex contains at least 28 accessory proteins which do not directly participate in the electron and proton transport function. A homologous complex which has 11 subunits in common with the respiratory complex I exists in cyanobacteria and chloroplasts. This complex might probably work as a NADPH:plastoquinone oxidoreductase being possibly involved in a cyclic photosynthetic electron transport. Homologues of the functional modules of the complex are also found in other bacterial electron transfer and ion transport proteins. The modular evolution of the complex and the possible origin of its modules are discussed in this paper.

Adenosine Triphosphate↗