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Biomedical subjects

M Hoffmann

Publications and source records attributed to M Hoffmann.

At least 19 recordsLinked to original sources

A simplified method for the determination of nitric oxide in biological solutions.

A new simplified procedure for determination of nitric oxide (NO) in biological solutions is described utilizing a new reducing system of nitric oxide prior to chemiluminescence. Advantages of the new method makes heating of the reducing solution unnecessary and avoids cooling and condensation of generated vapors. Only traces of acid with a high boiling point are used. The method permits analysis of small sample volumes (200 microL). The basal production of nitric oxide by freshly harvested endothelial cells ranged from 100 to 880 picomoles.

Animals

Analysis of the promoter of the cytochrome P-450 2B2 gene in the rat.

About 3 kb of the promoter region of the gene encoding cytochrome P-450 2B2 (CYP2B2) in the rat were sequenced and searched for potential cis-acting elements. Apart from putative binding sites for (liver-specific) protein factors, a region showing homology with the LINE 1 retrotransposon element was also found. Three proximal promoter fragments, encompassing nucleotides -579 to -372, -372 to -211, and -211 to +1, respectively, were shown to contain binding sites for multiple protein factors by bandshift analyses. The strongest protein-binding element, designated BRE (basic regulatory element), occurs between -103 to -66. Its structure is very similar to a negative control element in the murine cmyc promoter and displays a composite feature having a tandemly repeated sequence homology with the BTE (basic transcription element; Yanagida et al., 1990) separated by a CCAAA-box. The use of a deletion series of this template in in vitro transcription assays, provided evidence that the BRE serves as a major cis-acting element in the (regulated) transcription activation of the CYP2B2 gene.

Animals

[Mercury concentration in blood and urine--before and after the placement of dental amalgam fillings].

70 patients of dentist's surgery were given MOD amalgam fillings (non-gamma-2 amalgam) for molars. They were allocated for comparison to four groups defined by their treatment, i.e. the number of old and new restorations and whether a rubber dam was used. Blood and urine samples were collected at regular intervals before and during a 14-day period after treatment and tested for mercury concentration (Hg). Over the observation period the groups with the highest exposure (1-2 old restorations replaced by new ones) showed a tendency, in contrast to the less exposed groups (1 new filling with or without dam), towards increases (p less than 0.10) in group average Hg values of approx. 0.2 microgram/L (blood) and 0.3 microgram/g creatinine (urine) as acute treatment effects. The highest values recorded before and after the treatment, 3.3 micrograms/L (blood) and 16.5 micrograms/L (urine) are higher than normal but do not indicate any increase in the risk to health especially if they are not persistent.

Creatinine

[The importance of estradiol treatment by the transdermal route in preventing postmenopausal osteoporosis].

The authors selected 18 women in surgical menopause in order to evaluate the validity of estrogen treatment for the prevention of postmenopausal osteoporosis. Ten of these patients were given transdermal estradiol continuously for 12 months while the remaining eight served as untreated controls. Urinary hydroxyproline and bone density were assessed before and at previously determined intervals during treatment: the results showed the importance of estrogen replacement therapy for the prevention of postmenopausal osteoporosis.

Administration, Cutaneous

Fibrin degradation product D-dimer in the diagnosis of pulmonary embolism.

The study objective was to determine the specificity and sensitivity of plasma concentrations of D-dimer, a fibrin degradation product, as a marker for ongoing thrombotic and thrombolytic events in pulmonary embolism. A prospective study was performed in 74 patients with suspected pulmonary embolism who appeared in the emergency room with dyspnea and/or chest pain. The presence of pulmonary embolism was established by positive findings either in pulmonary angiography or lung scan. D-dimer concentrations were determined in all patients. In 11 patients with positive pulmonary angiography, D-dimer concentrations were monitored for 6-12 days. D-dimer concentrations were determined by a quantitative enzyme-linked immunoassay. Plasma probes of 26 patients (16 with/10 without positive pulmonary angiography) were re-assayed with a semiquantitative latex agglutination assay. D-dimer levels were significantly higher in patients with pulmonary embolism (greater than 1000 ng/mL in 41 out of 43) than in those without (less than 1000 ng/mL in all 21 patients) (p less than 0.01). The sensitivity and specificity for the ELISA were found to be 95% and 100%, respectively, for establishing the diagnosis of pulmonary embolism. In the latex assay the values were 81% and 60%, respectively. It is concluded that in patients with dyspnea and/or chest pain, determination of D-dimer in plasma by ELISA adds a valuable tool to the noninvasive diagnostic procedure for pulmonary embolism. From the time-course of D-dimer values we conclude that this assay might be valuable up to at least 6 days after symptom onset. The assay, however, is unreliable in malignancies or after surgery.

Adult

Spinal cord schistosomiasis. A clinical, laboratory and radiological study, with a note on therapeutic aspects.

Fourteen patients with schistosomiasis of the spinal cord are described. They fall into two groups: 7 patients had clinical and computer-assisted myelographic evidence of lesions in the conus medullaris or cauda equina, or both. The clinical picture in the remaining 7 patients was usually that of acute or subacute transverse myelitis with normal or equivocal CT myelographic appearances. Granulomas containing bilharzial ova were found in 2 female patients with conus swelling subjected to laminectomy and biopsy. In 1 of these the ova were identified as S. haematobium while in the second, unidentified bilharzial ova were found. A presumptive diagnosis of spinal cord schistosomiasis was made in the remaining 12 patients based on characteristic clinical and investigative profiles. All 13 patients tested showed evidence of bilharzial infection based on positive blood serology or the detection of bilharzial ova, or both. All but 1 patient showed at least one of the following abnormalities on CSF examination: pleocytosis, an elevated protein content and as indicated by the presence of oligoclonal IgG bands, an elevated IgG index and an increased CSF IgG synthesis rate. A CSF bilharzia enzyme-linked immunosorbent assay (ELISA) test, developed to indicate the presence of schistosomal infection within the theca, was found to be sensitive although not entirely specific for the diagnosis of spinal cord schistosomiasis. Eleven of the 14 patients showed rapid clinical improvement, 8 after praziquantel and corticosteroid treatment, 2 after operation and 1 spontaneously. Significant reductions in the CSF cell count, protein concentration and bilharzia ELISA titre, and in intrathecal antibody production, occurred following praziquantel and corticosteroid therapy. The CSF sugar level showed a significant rise. A reduction in conus size was observed in 3 patients when CT myelography was repeated after medical therapy. The normalization of most of the laboratory parameters after combined medical treatment with praziquantel and corticosteroids, together with clinical and radiological improvement, strengthened the presumptive diagnosis of cord schistosomiasis and supports the policy of early intensive medical treatment (as opposed to surgical therapy) for this condition when diagnosed on indirect evidence.

Adolescent

A transgenic approach to the study of peripheral T-cell tolerance.

There is now convincing evidence for the imposition of self tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we and other investigators have used transgenic technology to direct expression of a known "nonself" gene to a given extrathymic tissue. No lymphocytic infiltration was ever seen in transgene-expressing tissues, even if the mice were given normal syngeneic (nontransgenic) spleen cells intravenously or were stimulated with H-2Kb spleen cells. Infiltration did, however, occur in irradiated transgenic recipients of H-2Kb immune spleen cells. In MET-Kb mice, this infiltrate diminished with time, raising the possibility that peripheral tolerance may even have been induced in immune cells. H-2Kb-bearing skin was accepted in young RIP-Kb mice but rejected in older mice, which had lost more than 75% of their beta cells as a result of the overexpression of H-2Kb. This loss of tolerance thus occurred when the concentration of the tolerogen, H-2Kb, fell below some critical threshold. Following in vitro stimulation, spleen cells from young RIP-Kb mice could not kill H-2Kb-bearing targets, but could respond to third party targets. Thymus cells, on the other hand, could be stimulated to kill both targets, clearly indicating that tolerance was not imposed intrathymically. Spleen cells from older RIP-Kb mice (those that had lost most of their beta cells) killed both targets, which is in agreement with the in vivo data. Reactivity to H-2Kb was restored to young spleen cells by providing them with IL-2. Two hypotheses were proposed to account for the above findings: tolerance results either from the deletion or functional silencing of high-affinity effector cells or of regulatory, IL-2-producing helper T cells. As it is difficult to distinguish between these, we have produced a second series of transgenic mice (F3+) with rearranged TCR genes encoding an anti-H-2Kb TCR and derived "double-transgenic" (F3+RIP+) offspring by mating these mice with RIP-Kb mice. The transgenic TCR utilized the V beta 11 segment which can be detected by a monoclonal antibody. There were in the thymus very few CD4+ and very few CD4+8+ cells in both F3+ and F3+RIP+ mice and, in the double-transgenic mice, there was no evidence of deletion of CD8+V beta 11+ cells in the periphery although they showed tolerance to H-2Kb-bearing skin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Does interleukin-1 save B cells from paralysis? Studies with pre-B cells and antigen-reactive B cells.

The role of the second messenger cAMP in the differentiation of the pre-B cell line 70Z/3 and in the initial phase of the immune response of B cells, IgM antibody production is examined. Our data indicate that in these B cells, the elevation of intracellular cAMP levels can have two fundamentally different effects: it may dedifferentiate B cells and cause their disintegration (catabolic pathway) or it may induce their differentiation and maturation (anabolic pathway). The switch that determines which pathway B cells enter is set by interleukin-1. Our experiments indicate that intracellular cAMP levels rise in B cells when they interact with helper T cells in a cognate interaction. Given the dual effect that cAMP may have on the fate of B cells, activation or destruction, our data may be taken to suggest that helper T cells may direct B cells into catabolic or anabolic responses, depending on the availability of a costimulatory signal mediated by interleukin-1.

Animals

[The ruminal nitrogen metabolism in calves and sheep. 1. Studies in calves].

In a model experiment with calves supplied with duodenal re-entrant and rumen fistula resp. rations were tested that were energetically different (535 and 585 EFU cattle/kg DM) due to changing quotas of wheat starch and straw resp., dry matter intake being equal, and in which 45% of the crude protein came from soybean oil meal or urea resp. Due to the N-equivalent exchange of soybean oil meal by urea in rations for ruminating calves (130th day of life) the ammonia-N content in the rumen fluid, the quota of bacteria-N in the duodenal non-ammonia N (NAN) as well as the fermentation of crude plant protein in the ration were clearly increased. The iso-acid content in the rumen fluid and the utilization of the N available for bacteria N synthesis (N intake minus not degraded feed N in the duodenum) were reduced. An influence on duodenal NAN passage, on the apparent fermentation of the organic matter, on postruminal NAN digestibility and on the content of amino acid nitrogen as well as the amino acid composition of duodenal NAN could not be proved. A ca. 20% higher energy intake by ruminating calves did not have a clear influence on other parameters, with the exception of the reduction of the molar quota of acetic acid in favour of the quota of propionic acid in the rumen fluid.

Amino Acids

[The ruminal nitrogen metabolism in calves and sheep. 2. Studies in wethers].

Energetically differing rations which received ca. 45% of their crude protein from a supplement of soybean oil meal or urea were tested in a model experiment with adult wethers fitted with duodenal re-entrant cannulae or rumen cannulae resp. The N-equivalent exchange of soybean oil meal by urea in wethers resulted in a distinct increase of the NH3-N content of the rumen fluid, an increase of irreversible N losses and thus a worsening of the utilization of the available N for bacterial N-efficiency. A significant influence on duodenal NAN passage, on the apparent fermentation of the organic matter, on postruminal NAN digestibility and on the content of amino acid nitrogen as well as the amino acid composition of the duodenal NAN could not be detected. The increase of the energy level of the rations did not have a significant influence on the parameters of the ruminal N metabolism in the wethers. The studies with calves and adult wethers showed that a transposition of the parameters of ruminal N metabolism obtained to calves is not possible under the conditions given.

Amino Acids

A murine model of NK cell mediated resorption.

There is increasing evidence that some models of immunologically mediated murine embryo demise involve nonspecific lytic effector cells. In this paper, we use two double stranded synthetic RNAs, known as potent interferon inducers and NK cell activators, the Poly (I). Poly (C) and the less toxic Poly (I). Poly (C12U). These polynucleotides enhance fetal resorption rates in both resorption prone and none-resorption prone strains of mice. We have studied the kinetics of the phenomenon, and observed an anti-implantation-like effect of early injection during early pregnancy. The abortifacient effects can be adoptively transferred to naive recipients by spleen cells from Ds RNA injected donors. Such effects are abrogated if the cells are pretreated with anti-NK cell antiserum. The relevance of these findings to the survival of the conceptus is suggested.

Animals

[Cell proliferation in human cerebral tumors. In vivo study of 45 cases by incorporation of 5-iododesoxyuridine].

A method to study the proliferation of human brain tumors, is presented. Non radioactive 5-Iododeoxyuridine (2.4 gr) infused over a 24 hours period is detected in situ on histologic section by an immunological technique (peroxidase-anti-peroxidase) using a specific anti-Iododeoxyuridine antibody. This exploration utilised in 45 patients is easy, reliable and harmless. All cells which enter in S phase of cellular cycle during the infusion are labelled. So the cellular kinetics of all the brain tumor cells (malignant cells, inflammatory stroma reaction cells, reactive astrocytes, endothelial and muscular cells of the vessels) are detected on the same histological section, as well as all the others proliferative cells of the body (leukocytes, primitive tumor of the metastatic brain localisation...) if multiples biopsies are done. 8 of 9 gliomas of low histological malignancy (grade I and II) have a slow cellular kinetic. The 23 astrocytomas of different histological malignancy (grade III and IV) have variable proliferative speed (7 very fast, 8 fast and 8 slow). Only the large cells of the pinealoma are very proliferative, the lymphoid stroma is quiescent. The 5 metastasis have a slow to very fast kinetic without correlation with the cellular differentiation except in one case (important differentiation and slow cellular proliferation). The 5 lymphoma cells kinetics are well correlated with the histologic differentiation (3 large cells poor differentiated lymphomas and very fast kinetic, 2 better differentiated and slower proliferation). The 2 meningiomas proliferate slowly. The biochemical and histopathological grounds of the presented method and the limits of quantification are discussed. This method is compared with this using Bromodeoxyuridine. The correlation between proliferation and histologic malignancy is analysed. The use of cytokinetic results for therapeutic and prognosis need further statistical anatomoclinical studies.

Adult

[The effect of energy concentration and source on the use of feed protein and NPN in lambs. 3. Allantoin excretion and microbial protein synthesis].

In an N balance experiment with male crossbreeding lambs at an age of 3 ... 4 months four different rations were given differing in energy concentration (high greater than 700 EFU cattle/kg DM and low less than 650 EFU cattle/kg DM) and in the energy source (sugar, starch or crude fibre) with crude protein intake being almost equal. The rations contained 2% urea. Microbial protein synthesis in the rumen was assessed according to ROTH and KIRCHGESSNER (1978) (1), RYS et al. (1975) (2) and BICKEL-BAUMANN and LANDIS (1986) (3) on the basis of allantoin excretion in urine. The highest ruminal protein synthesis quotas were 868 ... 921 mg protein N per kg LW0.75 in (2). In (3) 723 ... 766 mg protein N/kg LW0.75 were synthesized. From the 15N labelling of the supplemented urea and the excreted allantoin it could be calculated that 26 ... 40% of the microbial protein resulted from the urea-N of the ration. Despite a high crude protein content of the ration of between 16 and 17% in the DM and a relation of NPN: pure protein of 0.95 the utilization of the NPN in the ration was relatively high but slightly lower than the utilization of pure protein. The variants with higher energy concentration showed as a tendency higher allantoin excretion in spite of slightly lower dry matter intake and a slightly higher NPN utilization than the variants with lower energy concentration.

Allantoin

[The effect of pregnancy and lactation on digestive processes in sheep].

The average passage time, the rumen fluid volume and the digestibility of the organic matter were determined in addition to 3 individual feeding experiments with fertility oriented crossbreed ewes, which received pelleted straw-concentrate mixtures. The average passage time of the feed particles through the digestive tract is shorter in pregnant animals than in lactating ones. It is longest in non-pregnant sheep. High quotas of straw and coarse particles prolong the passage time, increasing feed intake and supplements of long straw shorten it. The volume of rumen fluid is lower in ewes fed ad libitum in the stage of late pregnancy and after lactation than during lactation. The rumen fluid volume is also lower in restrictively fed animals during the stage of late pregnancy than during lactation. In animals in the stage of late pregnancy it correlates negatively with the weight of the litter. On an average of all experiments at maintenance level the digestibility of the organic matter in ewes in the 4th month of pregnancy gravidity amounted to 56.6%, in the 2nd month of lactation to 59.8% and in wethers to 59.5% Due to an increase of energy intake from maintenance to 2. maintenance digestibility of the straw-concentrate mixture with 40% straw decreased by 5.5 units and of that with 60% straw by 17.8 units in the period before delivery. Pregnancy in the 4th month resulted in a digestion depression of between 3.0 and 5.8 units.

Animals

[Consumption and ruminating behavior of sheep. 4. Experiments on young female sheep in different rearing intensities].

In the framework of two rearing experiments with female merino meat sheep, measurings of the consumption and ruminating behaviour were carried out. Animals raised with a lot of roughage ruminated longer both in their lamb and young sheep periods. An increased quota of roughage in the ration increased both the ruminating time and the number of chewing moves and cycles significantly for young sheep. The dry matter intake capacity of animals raised with high quotas of roughage was by 14 and 8% resp. higher in the lamb period and by 26 and 18% resp. higher in the young sheep period. Rations with 24% chopped and dried green fodder and 11 ... 14% resp. crude fibre brought about a period of more than 6 hours ruminating and a minimum of 22,000 ruminating movements per day for lambs. Young sheep raised with high quotas of roughage showed an increased ruminating activity in subsequent periods of sole feeding with roughage.

Animal Feed

[Consumption and ruminating behavior in sheep. 5. Continuous registration and recording of consumption and rumination dependent jaw movements in sheep based on acceleration measurements].

A method of the registration of the feed intake and ruminating behaviour of sheep which uses piezoelectric converters was tested. The appliance-technological solution and the feasibility and routine measurings are described. It showed that measurings on the basis of acceleration registration produced similar results as the 'halter method with plate feelers' used so far and that disturbance of the test animals is reduced.

Animal Feed