Bulk-doping-controlled implantation site of boron in silicon.
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Biomedical subjects
Publications and source records attributed to B Fischer.
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32 patients with HIV infection presenting with fever or abnormal chest radiograph or both were investigated at the University Hospital of Mainz (FRG). Fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was undertaken in each patient, additionally other methods were used for isolating pathogens (i.e. urine sample, stool and blood culture etc.). In 26 patients one or more complicating diseases were documented, in six persons no reason for fever or pulmonary symptoms could be detected. 21 patients had a pulmonary complication, 13 were found to have pneumocystis carinii pneumonia. Bacterial lung diseases were diagnosed in seven individuals (three caused by M. tuberculosis, two by S. pneumoniae, one by E. cloacae and one by S. aureus). One nonspecific interstitial pneumonitis was diagnosed. By other diagnostic procedures 25 non-pulmonary complications were established. -Fiberoptic bronchoscopy is most accurate for the detection of pulmonary pathogens in HIV infected persons when transbronchial biopsy and bronchoalveolar lavage is combined, especially in pneumocystis carinii pneumonia. Bronchoscopy should be performed also if the chest radiograph is normal.
The development of cultured rabbit preimplantation embryos grown in standard media (Ham's F-10 or BSM II supplemented with bovine serum albumin (BSA) or homologous serum) or in Ham's medium supplemented with uterine flushings was compared. The uterine flushings derived from donors of 0.5-6 years of age. Uterine flushing supplemented media were used natively or after treatments like sterilization by filtration, lyophilization, three times freezing/thawing, heat denaturation, dialysis, or ultrafiltration. Compared with in vivo controls, embryonic growth was substantially reduced during in vitro culture, demonstrably by smaller diameters and impaired cell proliferation (measured by thymidine incorporation). The growth retardation was more pronounced in blastocysts (recovered at day 4 post coitum [p.c.]) than in morulae (recovered at day 3 p.c.). Development in uterine flushing media was notably better than in standard media but did not comply with in vivo development. Highest thymidine incorporation was observed in media with increased concentrations of uterine secretions and after sequential supplementation of flushings from subsequent progestational stages. Advanced donor ages, heating up to 80 degrees C, freezing, and lyophilizing did not affect incorporation data statistically significantly, whereas sterilization by filtration, ultrafiltration, and dialysis led to a significantly reduced thymidine incorporation in the cultured embryos. The positive effects of uterine flushing supplementation are attributed to the supply of components more adjusted to the needs of the cultured embryos and/or to a reduction of pathological effects in vitro like washing out of nutritive and regulatory components from the embryo into the surrounding culture medium.
Two rhesus monkeys were trained to make saccadic eye movements from a central fixation point towards a peripheral target. Saccadic reaction times (SRTs) were measured in the gap paradigm (200 ms pause between offset of fixation point and onset of peripheral target). Target position for extensive training (SRTs of 150 to 250 saccades were collected per day) was four degrees eccentric in the lower quadrant of the visual field contralateral to the intended lesion site in area V4. For control the monkeys were also trained for target positions either in the lower quadrant ipsilateral to the intended lesion site or in the upper visual half field. After several weeks of training a bimodal distribution of saccadic reaction times, one peak at 85 ms (express saccades) and the other around 160 ms (regular saccades) was obtained for each target position. Local injection of ibotenic acid into the 4 deg representation of area V4 resulted in a unimodal distribution of saccadic reaction times (over 90% express saccades) towards the corresponding target position, leaving the distribution of reaction times for the control position unchanged. Recovery began after 5 days and was complete 8 to 10 days after the injection. From these results we conclude that V4 is involved in the generation of the longer latency peak in the distribution of saccadic reaction times by delaying the initiation of visually guided saccades.
Saccadic reaction times (SRT) were measured in a simple task: subjects had to make saccades from a central fixation point to peripheral targets, which appeared randomly 4 deg to the left or to the right. In the first test the fixation point went off before the target appeared (gap trials); in the second test it remained on the screen (overlap trials). The distribution of SRTs for trained normal adults (N = 4), untrained normal adults (N = 11), untrained normal children (aged 9-11 years, N = 9), untrained normal teenagers (aged 15-17 years, N = 8), dyslexic children (aged 9-11 years, N = 15), and dyslexic teenagers (aged 15-17 years, N = 5) were compared, with special emphasis on the number of express saccades, ie saccades with extremely short reaction times (100-120 ms, under the present conditions). In normal adults with the gap paradigm, the distribution of reaction times typically exhibits two or three modes (express saccades, fast regular saccades, and very few slow regular saccades), whereas in the overlap paradigm only one or two modes (few fast regular saccades and many slow regular saccades) are obtained. On average, normal children produce more express saccades than naive normal adults. Dyslexic children produce more express saccades than the normal age-matched controls. Among the dyslexic children, four different types of abnormalities in their reaction times were encountered. The group of dyslexic teenagers was characterized by a larger number of express saccades at the expense of fast regular saccades in gap trials and by fewer express saccades and fewer fast regular saccades in overlap trials when compared to the age-matched control group. It is concluded that the abnormal patterns of saccadic reaction times reflect defects in the system of visual attention and/or in its control over the oculomotor system, rather than indicating a defect in the oculomotor system itself. In this context, symptoms of dyslexia appear as a combination of attentional deficits and irregular timing of saccadic eye movements.
Pseudohypoparathyroidism (PHP) is a rare disorder that might be caused by an hereditary defect in the G protein system. These membrane-bound proteins are responsible for the transduction of biological signals through the outer cell membrane. The investigation of 22 patients with PHP showed a symmetric sensorineural hearing loss in 63.6% of the subjects. In erythrocyte membrane preparations from blood samples of 15 of these patients, we measured the concentration of the stimulatory Gs protein and the inhibitory Gi protein by means of the Western blot analysis using selective antibodies against alpha-subunits of G proteins. In nine of the 15 cases (60%), we found a distinct decrease in the amount of the Gs protein with a partial preponderance of the Gi protein. These patients had a considerable symmetric sensorineural hearing loss. Pathophysiological mechanisms and the possible role of G proteins in the inner ear are discussed.
We used a monoclonal antibody against an epitope located in the N-terminal moiety of the rat glucocorticoid receptor to identify the glucocorticoid receptor-containing cells in the rat pancreas. Monospecific polyclonal antisera against insulin, glucagon, somatostatin, and amylase were applied to serial sections in colocalization studies to identify the respective endocrine and exocrine cells. Glucocorticoid receptor immunoreactivity was exclusively present in nuclei and cytoplasm of the beta-cells of pancreatic islets. Western blots using the glucocorticoid receptor antibody resulted in identical 94K immunoreactive proteins in both liver and pancreas. After adrenalectomy, the glucocorticoid receptor immunoreactivity of beta-cells decreased significantly. A computer-assisted method of semiquantitative evaluation of the glucocorticoid receptor immunoreactivity demonstrated a significant decrease in the staining intensity of the beta-cells by 23.5% and in that of insulin antibodies by 10.4%, while amylase immunoreactivity was only slightly decreased. Serum levels of corticosterone determined by RIA decreased from 225 micrograms/ml in sham-operated animals to 55 micrograms/ml in animals 14 days after adrenalectomy, while the tissue content of amylase decreased by 45%. The immunohistochemical findings give circumstantial evidence of the presence of glucocorticoid receptor in beta-cells. We interpret our data as indicating an indirect effect of glucocorticoids on amylase synthesis via a glucocorticoid-insulin-exocrine cell pathway.
Intact fibrin monomer, the early fibrin degradation product (X-fragment), late fibrinogen degradation products (fragments D and E), fibrinogen cyanogen bromide fragment FCB-2, and isolated peptide chains of fibrinogen and fibrin were investigated for their ability to replace fibrin in the stimulation of one-chain tissue-type plasminogen activator. They were also investigated for their ability to stimulate plasminogen activation by one-chain tissue-type plasminogen activator, which occurs via ternary complex formation. The stimulatory effect of the different fibrin/ogen products decreased in the order: fibrin X-fragment greater than fibrin monomer greater than CNBr-fragment FCB-2 greater than fibrin alpha-chain. Fibrin beta/gamma-chains and fibrinogen peptide chains were found to be weak stimulators. Fibrinogen fragments D and E have almost no effect. The amidolytic activity of one-chain tissue-type plasminogen activator was stimulated by intact fibrin monomer and somewhat more strongly by fibrin X-fragment. This stimulation by fibrin monomer, which occurred via an increase in the kcat value, was competitively inhibited by isolated fibrin alpha-chain (Ki = 0.12 mumol/l). The results show that the fibrin-mediated stimulation of plasminogen activation occurs when both one-chain tissue-type plasminogen activator and plasminogen are bound to fibrin, and that this process is essentially independent of the conformation of the fibrin molecule. In comparison, the fibrin-dependent stimulation of the amidolytic activity of one-chain tissue-type plasminogen activator is a more complex process, which depends on the correct conformation of the fibrin molecule.
Tissue-type plasminogen activator (t-PA) is an important component of the fibrinolytic system. t-PA is released into the circulation as a one-chain peptide with little enzyme activity. There exist several mechanisms which enhance plasminogen activation rate by t-PA: 1. activation of enzyme activity of one-chain t-PA by fibrin binding; 2. activation of enzyme activity by transforming one-chain to two-chain t-PA by plasmin; 3. stimulation of plasminogen activation by forming a ternary complex of t-PA, plasminogen and fibrin; 4. stimulation of plasminogen activation by forming Lys-plasminogen, which has a higher affinity to fibrin and is a better substrate for t-PA than Glu-plasminogen; 5. enhancement of ternary complex concentration after initiation of fibrinolysis due to tighter binding of t-PA and plasminogen to partially degraded fibrin.
Knowledge of the radiopacity of bromine-containing hypnotics and of halogenated hydrocarbons has led to numerous recommendations and speculations. Supported by own investigations the sensible application of a rapid radiological determination in the practice of clinical toxicology is discussed. This should always be carried out, if solvent residues, gastric contents or gastric lavage fluid are available, a ingestion is suspected, and the result of chemical analysis is not promptly obtainable. However, a hint at the group of halogenated hydrocarbons is only possible, if additional information about miscibility with water is accessible. Revealing the presence of radiopaque material in tablet or liquid form by radiologic studies of the abdomen may be very helpful for the rapid evaluation of symptomatology and first therapeutic consequences, but it does not allow any chemical identification of the poison.
In 32 patients infected with HIV with unclear fever and/or pulmonary infiltraes, a fiberbronchoscopy (FB), with transbronchial lung biopsies (TBB) and bronchoalveolar lavage (BAL) was carried out. Thirteen of these patients had pneumocystis carinii pneumonia (PCP), three patients tuberculosis of the lungs, two patients pneumococcal pneumonia, and one patient each had a staphylococcal pneumonia, an enterobacter cloacae pneumonia, and an unspecific alveolitis. Thus, 66% of the patients proved diagnostically diagnosable by FB, so that appropriate therapy could be instituted. It proved possible to diagnose 77% of the PCP cases by TBB, and 62% by BAL. Thus, the combined use of both procedures increases the sensitivity of FB in detecting PCP. In two patients with PCP, no pulmonary infiltrations were to be seen. In no case was FB associated with any complications that required treatment. Through the additional use of other diagnostic procedures for identifying the organism, it proved possible to establish a total of 46 individual diagnoses. These results underscore the frequency of multiple infections in this group of patients.
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Although there are a number of physiological states associated with an increase in body temperature, eg, nonseptic and septic fever or exercise, the effects of hyperthermia on intermediary metabolism in vivo have received little attention. The current study was undertaken to examine the peripheral metabolism of ammonia and ammonia-related amino acids using a model of exogenously induced mild hyperthermia in nonfebrile subjects. Arteriovenous levels of metabolites were measured in subjects with known cerebrovascular insufficiency. Peripheral exchange of these metabolites was monitored before, during, and after hyperthermia to an average temperature of 38.5 degrees C. All subjects showed an increase in plasma ammonia and glutamate. There was also an associated peripheral production of ammonia and an uptake of glutamine and alanine by the skeletal muscle tissues. The exchange of glutamate was not affected. These findings indicate that hyperthermia is associated with a nitrogen-sparing effect, the mechanism of which is yet unknown.
Reaction times of saccades and of hand movements to a single visual target were measured and correlated on a trial-by-trial basis. The absolute values of the reaction times and their correlations depend on whether the fixation point, from which both eye and pointing movement started, remained visible (overlap) or was turned off some time before the target appeared (gap). Under overlap conditions long reaction times were obtained exhibiting large scatter and high correlations. Under gap conditions short reaction times (including express saccades) occurred with a small scatter and almost no correlations. It is concluded that the preparation of the saccade must be completed before the corresponding pointing movement can be initiated but not vice versa.
In an attempt to clarify whether or not glutaraldehyde molecules contribute to the effective osmotic pressure of the fixative solution the ultrastructure of noncultured and in vitro-cultured day 1, 3 and 4 rabbit embryos was evaluated. Total osmolarity of the fixative solution (200-800 mosm) was only varied by changing the aldehyde concentration, whereas the vehicle osmolarity (145 mosm) remained unchanged. Optimum preservation in all embryonic stages was obtained when total osmolarity of the fixative solution was 285-340 mosm. Higher (480-800 mosm) or lower (250 mosm) osmolarities of the fixative solution led to alterations mainly in mitochondria and smooth-surfaced endoplasmic reticulum. Shrinkage of cells and condensation of the cytoplasm occurred only occasionally. Compared with early cleavage stage embryos blastocysts were generally more susceptible to hyperton and hypoton fixative solutions. In vitro culture for 24 h per se did not have any influence on the fixation.
The development of synchronously and asynchronously transferred rabbit morulae (recovered at Day 3 p.c.) and blastocysts (recovered at Day 4 p.c.) was investigated before the anticipated time of implantation. The results obtained with various techniques (evaluation of gross morphology, measurement of diameter, thymidine incorporation, light and electron microscopy) led basically to the same conclusions. Embryos being asynchronously transferred to the uterus of recipient rabbits survived, at least in terms of certain cellular functions like cell proliferation, for more than 2 days. Development, however, was clearly retarded and ultrastructural examination revealed substantial cell damage. Some blastocysts showed, even after 3 days, normal growth and cell proliferation indicating considerable differences between individuals in the ability to compensate for suboptimal developmental conditions before implantation. In general, this ability was greater in the transferred Day-3 morulae than in the Day-4 blastocysts. Embryonic growth and the ability to dissolve the zona pellucida, to synthesize crystalloid bodies and to differentiate extraembryonic endoderm indicated the maintenance of some developmental functions under asynchronous conditions. Blastocyst development was influenced by the progestational stage of the recipient. At 1 day after transfer into asynchronous older uteri, blastocyst diameters were larger and cell proliferation was increased compared with all other groups, suggesting an attempt of the blastocyst to adjust to the more advanced maternal milieu. Development in asynchronous younger uteri was delayed. No comparable differences in development were found in cultured embryos for which the media had been supplemented with flushings from the same progestational uterine stages as used for transfer. Thymidine incorporation in cultured embryos did not differ between the various supplements (P greater than 0.05) and was generally lower than in chronologically aged asynchronously transferred embryos (P less than 0.05 for Day-3 and P less than 0.001 or P greater than 0.05 for Day-4 embryos).
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An otherwise normal female rhesus monkey executed large saccadic eye movements (macro square wave jerks) when required to attentively fixate a small visual target (fixation point). The jerks were observed exclusively in this specific testing situation. They occurred periodically at a frequency of 2.04 + - 0.18 Hz to the right side with an amplitude of 23.5 deg. Direction of the jerks was about 3-4 degrees downward from horizontal. These parameters remained constant throughout the several months of daily recording. No jerks were executed during periods when the behaviourally important target was absent or substituted by another, behaviourally non-relevant visual stimulus. The monkey could perform normal visually guided saccades as well as smooth pursuit eye movements, but with the jerks always superimposed, when the monkey paid attention to the visual target. Histologic inspection of the brain revealed the presence of an incapsulated nematode in the cortex of lobulus simplex of the right cerebellar hemisphere, i.e., in a region involved in oculomotor control.