Search PubMed⌕ Search

Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 955 records · Page 53Linked to original sources

CCK-8 and gastrin plasma levels in cholecystectomized and colorectal cancer patients.

The elevated incidence of large bowel carcinoma after cholecystectomy has long been controversial. The pathomechanism of this entity, however, is still unclear. Many authors have demonstrated a correlation between cholecystokinin (CCK) and gastrin levels and the occurrence of colorectal cancer. As yet, no clear data are available on the potential impact of cholecystectomy on CCK level alterations. Moreover, no reports have yet been published on CCK receptors. We have investigated the role of CCK-8 and gastrin plasma levels in patients with prior cholecystectomy and CCK receptor levels in patients with colorectal cancer. 125 patients entered a prospective study. Of these, 45 served as controls. 40 patients had prior cholecystectomy, 5 patients underwent cholecystectomy during the ongoing trial. 35 patients had a colorectal cancer, 5 of these had prior cholecystectomy. No patient had elevated CCK-8 plasma levels. Gastrin levels were slightly elevated in 2 patients. There was no correlation between large bowel carcinoma and CCK-8 and gastrin levels. Elevated CCK-8 levels following cholecystectomy occur neither immediately after surgery nor on a long-term basis. Immunohistochemical studies in patients with colorectal cancer showed no CCK receptors in the normal colonic or tumor tissue. These findings are contrary to gastrin receptor data.

Cholecystectomy↗

Morphological and functional consequences of chronic epilepsy in rat hippocampal slice cultures.

We have developed an in vitro model of chronic epilepsy in order to study the consequences of prolonged periods of epileptic activity. After applying the convulsants bicuculline and/or picrotoxin to mature rat hippocampal slice cultures for 3 days, large numbers of swollen and vacuolated cells were observed throughout all hippocampal subfields. The number of dendritic spines of pyramidal cells was massively reduced. These changes were similar to those observed previously in post-mortem studies of hippocampal tissue from human epilepsy patients. Intracellular recordings from CA3 pyramidal cells revealed that spontaneous synaptic activity was greatly reduced in treated cultures. gamma-Aminobutyric acid-mediated inhibition was apparently not affected by sustained convulsant activity, although synaptic excitation was markedly depressed. Acute re-application of bicuculline to treated cultures elicited, upon stimulation of the mossy fibre tract, a typical interictal burst lasting several hundred milliseconds, with a wave form similar to those occurring in untreated cultures, but of a shorter duration. In contrast, ictal bursts (lasting tens of seconds), which always occur spontaneously in control cultures during initial perfusion of bicuculline, were not observed in treated cultures. These pathological changes were reversible when treated cultures were returned to normal medium for 1 week. The surviving cells had a healthy morphology and a normal complement of dendritic spines. Spontaneous synaptic activity was normal, and ictal bursts occurred spontaneously upon perfusion of bicuculline. The findings suggest that the morphological and functional changes are a consequence, rather than a direct cause of epilepsy.

Animals↗

Effects of methylprednisolone on the energy metabolism of quiescent and ConA-stimulated thymocytes of the rat.

The short-term effects of high concentrations of Methylprednisolone (MP) on the energy metabolism of quiescent and Concanavalin A-stimulated rat thymocytes were investigated in vitro. Concanavalin A (ConA) stimulated the respiration rate of quiescent thymocytes by 35%. Addition of more than 0.15 mg MP/10(7) cells to ConA-stimulated cells reversed this respiratory stimulation; in addition, higher concentrations of MP caused a similar progressive decrease in the rate of respiration of both quiescent and ConA-stimulated cells. Similarly, the stimulation of respiration by ConA was greatly reduced in MP-treated cells. MP addition lowered cytoplasmic [Ca2+] and, at high concentrations, abolished the ability of ConA to increase [Ca2+]. Thus MP both reverses and prevents the immediate stimulation of thymocytes by ConA. In quiescent thymocytes, MP strongly inhibited that part of the oxygen consumption used to drive the cycle of Na+ influx across the plasma membrane and Na+ efflux on the Na+K(+)-ATPase, but did not inhibit oxygen consumption used to drive protein synthesis. In ConA-stimulated thymocytes MP had the same effects and also strongly inhibited oxygen consumption dependent on the cycle of Ca2+ influx across the plasma membrane and Ca2+ efflux on the Ca(2+)-ATPase, but had little effect on oxygen consumption used to drive RNA and DNA synthesis. These results show that MP prevents cation cycling in thymocytes (either by preventing cation influx or by inhibiting cation pumps) and prevents mitogenic stimulation of the cells. The high MP concentration required and the speed of onset of the effects (less than 30 s) provide strong evidence that these effects of MP are not mediated by glucocorticoid receptors and subsequent activation of gene expression. They may be caused by direct effects of MP on the properties of the plasma membrane. These effects are considered to be, at least partially, responsible for the beneficial results that currently have been obtained using MP megadoses in various clinical situations.

Adenosine Triphosphate↗

Hydrogen peroxide in expired breath condensate of patients with acute respiratory failure and with ARDS.

OBJECTIVE: Measurement of hydrogen peroxide concentrations in breath condensate of mechanically ventilated patients with ARDS and with risk factors for developing ARDS. DESIGN: Open study in intensive care patients. SETTING: Intensive care units of the Clinics of the University of Göttingen, a primary care center. PATIENTS: 10 post-operatively ventilated patients as a control group and 26 patients with acute respiratory failure, 7 of them with ARDS, 12 with polytrauma, 4 with pneumonia, 3 with cardiogenic or nephrogenic pulmonary edema. INTERVENTIONS: None. MEASUREMENTS: Breath condensate was collected by a special cold trap and was analysed for H2O2 by a chemiluminescence method. Daily measurements were performed for 4.2 +/- 2.6 days (mean +/- SD) as soon as possible after manifestation of respiratory failure. RESULTS: Patients with acute respiratory failure exhibited higher H2O2 concentrations than control patients (median 95 nmol/l, range 76-144 nmol/l), with the highest median value found in the ARDS group (552 nmol/l, range 154-893). After clinical improvement, H2O2 concentrations decreased to the range of the control group. CONCLUSION: Since high concentrations of H2O2 in breath condensate were only found in patients with ARDS or with risk factors for ARDS, the results add to the existing evidence that reactive oxygen species are associated with some acute lung diseases.

Adolescent↗

Cigarette smoking, blood lipids, and baroreceptor-modulated nociception.

Activation of arterial blood pressure has been shown to influence higher central nervous activity. In animals, induction of sleep-like states and increases of seizure and pain thresholds in response to baroreceptor stimulation have been reported. In certain human groups, mechanical stimulation of the carotid baroreceptors also increases pain thresholds. The present paper examines the hypothesis that smokers show baroreceptor dependent antinociception as compared to non-smokers. It is speculated that one effect which rewards smoking is the nicotine induced phasic blood pressure increase which leads to baroreceptor stimulation and dampens pain perception. One hundred and twenty subjects were investigated using a recently developed mechanical baroreceptor stimulation technique and an electrical pain stimulus. The group of heavy smokers showed the predicted effect: their pain thresholds were enhanced during conditions of increased baroreceptor activity as compared to the control condition. The group of medium, light and non-smokers, however, did not show this effect. Neither blood lipid levels nor diastolic or systolic blood pressure paralleled the group differences on baroreceptor dependent antinociception. In heavy smokers, the nicotine induced phasic blood pressure increases might have baroreceptor dependent pain dampening effects, which might be among the reinforcing qualities of smoking.

Adult↗

Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients.

Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen, D-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p < 0.005, p < 0.02), factor VII activity (p < 0.0002, p < 0.002), factor VII antigen (p < 0.0001, p < 0.001), protein C (p < 0.003, p < 0.05), and lipid peroxides (p < 0.02, p < 0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p < 0.001) and protein S (p < 0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.

Adult↗

Cellular localization of tissue factor in human breast cancer cell lines.

Expression of tissue factor (TF), the cellular receptor of clotting factor VII/VIIa, is a feature of certain malignant tumours. The TF gene has been classified as an immediate early gene responsive to serum and cytokines. Thus, the regulation of TF gene expression seems to play a role in cell growth. Recently, we have shown that constitutive TF expression in MCF-7 breast cancer cells is modulated by such growth factors as EGF, TGF alpha, and IL-1. The present study deals with the immunocytochemically detectable cellular distribution of TF in human breast cancer cell lines MCF-7 and MaTu stimulated by EGF and TGF alpha. In MCF-7 cells growing logarithmically, stimulation led to a significant increase of TF mRNA after 2 h (in situ hybridization, Northern blot) and to maximum TF expression after 6 h (immunohistochemistry). When decorated by monoclonal antibodies, TF protein showed a pronounced localization at ruffled membrane areas, cell edges, and processes of spreading cells after 6 and 20 h. In more flattened cells TF was concentrated in peripheric lamellae and microspikes communicating with neighbouring cells. After epithelial colony pattern had established, TF was predominantly accumulated at the intercellular boundaries. The vary same distribution patterns as seen in MCF-7 cells were true for the stimulated MaTu cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Changes in cytokeratin, vimentin and desmoplakin distribution during the repair of irradiation-induced lung injury in adult rats.

The expression of cytokeratins, desmoplakin and vimentin has been studied immunohistochemically in the rat lung injured by x-irradiation using 14 well characterized monoclonal antibodies. A time-dependent relationship between the cytokeratin expression pattern and the morphological alterations observed was apparent. A cytokeratin 8 and 18 expression in normally cytokeratectable even at 3-6 h after irradiation. Between 14 days and 2 months, a remarkable heterogeneity in the epithelial cell cytokeratin pattern and an increasing immunoreaction for desmoplakin was found. In terminal bronchial epithelial cells, a heterogeneous CK8, 18 and 19 staining and a neoexpression of cytokeratins 4 and 7 was detected. Finally, peribronchiolar and vascular smooth muscle cells were cytokeratin-positive. At 6 months after irradiation, cytokeratin 13 and vimentin were focally present in bronchial epithelial cells and atypical type I and II pneumocytes as well as scattered epithelioid cell complexes were noted. During the course of injury, a loss of type III alveolar epithelial cells was found, which was characterized in the rat by a specific globular cytokeratin pattern and restricted immunoreactivity with cytokeratin-specific antibodies. These results show that the expression pattern of cytokeratins is a sensitive marker in monitoring epithelial alterations during lung injury.

Animals↗

Misuse mode and effects analysis--an approach to predict and quantify misuse of child restraint systems.

It is known that misuse of Child Restraint Systems (CRS) is widespread and must be considered as a major threat to the safety of children. In this paper a quantitative method of predicting and assessing misuse of CRS is proposed. The process, called "Misuse Mode and Effects Analysis (MMEA)" assesses the likelihood of occurrence of potential misuse modes and their effect on safety before and after corrective actions. The effectiveness of the proposed method is demonstrated in the assessment of a number of commonly used CRS.

Child, Preschool↗

"Probing" the nature of the CNV.

A widespread depolarization in the dendritic trees of cortical pyramidal neurons generates surface-negative potentials. In turn, such potentials may indicate facilitatory processes, while positive-going waves may result from a lowering in cortical excitability. Accordingly, we may expect the processing of "probe" stimuli presented during surface-positive waves, i.e., during phases of lesser excitability, to be inhibited and probes presented during surface-negative waves to be facilitated. This hypothesis was tested by presenting acoustic probe stimuli at various points in time during a forewarned reaction time task. The warning stimulus (WS) elicited a late positive complex followed by a negative slow potential shift (CNV). In 75% of the total of 120 trials a probe could be presented 1.5 sec prior to the WS interval, 0.5, 1, 1.5 or 2 sec after the onset of the 3 sec visual WS, and 3 sec following the imperative signal (WS offset, requiring a fast button press response), while 25% of the trials were without any probe. Only one probe occurred during a trial. The EEG was recorded along the midsagittal line; responses to the probes were evaluated by reaction time (RT) and probe-evoked potentials. RT to probes presented late in the anticipatory interval were speeded up and probe-evoked potentials were enhanced during this interval, in parallel to the development of the slow potential and the CNV in particular. Results suggest that probe stimuli presented during the development of the CNV were processed more intensely, thereby supporting the hypothesis that slow cortical potentials indicate the timing of excitability in cortical neuronal networks.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Cochlear place-frequency map in the marsupial Monodelphis domestica.

In order to determine the place-frequency map of the cochlea in the marsupial Monodelphis domestica, iontophoretic HRP-injections were made at several locations in the ventral cochlear nucleus. Prior to iontophoresis the auditory neurons at these locations were characterized electrophysiologically. The resulting distribution of retrogradely labeled cochlear spiral ganglion cells was analysed by means of a three dimensional reconstruction of the cochlea. The map was established for frequencies between 2.4 and 44.5 kHz, corresponding to positions between 95 to 14% of basilar membrane length (base = 0%). The maximum slope amounted to 1.8 mm/octave. Over the basal-most 60% of the cochlea the slope of the place-frequency map was larger than 1.5 mm/octave, further apically the slope rapidly decreased to values below 0.8 mm/octave. The shape of the cochlear place-frequency map is similar to that described in placental mammals.

Acoustic Stimulation↗

Heterogeneous Dolichos biflorus lectin binding to a subset of rat alveolar macrophages in normal and fibrotic lung tissue.

The distribution of Dolichos biflorus lectin in the rat lung and during fibrosis after irradiation was investigated by lectin histochemical and electron microscopical techniques and double immunofluorescence labelling with the monoclonal antibodies RM-1 and ED-1. The results indicate a selective reaction of Dolichos biflorus lectin with a subpopulation of alveolar macrophages. No binding of the lectin was detectable in ED-1-positive macrophages but strong staining occurred in a part of the RM-1-positive cell population. In fibrotic lung specimens an increased number of Dolichos biflorus lectin-positive macrophages was found in which focally ED-1 reactive and RM-1 negative cells appeared. The finding of changing lectin binding pattern in a radiation-induced lung model emphasizes the suitability of the Dolichos biflorus lectin as a marker of macrophage activation or functional specialization.

Animals↗

Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth.

Four monoclonal antibodies (MAbs) specific for the extracellular domain of the human erbB-2/HER2 protein (FRP5, FSP16, FWP51 and FSP77) have been isolated (Harwerth et al., J. Biol. Chem., 267, 15160-15167, 1992). In this paper we describe the effects of erbB-2 specific MAb administration on the tumorigenic growth of human erbB-2 transformed NIH3T3 cells implanted into athymic nude mice. Two antibodies, FWP51 and FSP77, inhibited the onset of tumour growth, while the administration of FRP5 and FSP16 did not affect tumour growth. In addition, administration of MAbs FWP51 and FSP77 led to a retardation in the growth of established tumours. Treatment was not curative in that tumours regrew within two weeks of the final treatment. The administration of a combination of MAbs FWP51 and FSP77 which react with two distinct regions on the erbB-2 molecule was more effective than treatment with either MAb alone. The two growth-inhibitory antibodies were also effective in the treatment of tumours established from SKOV3 cells, a human ovarian tumour cell line with high levels of the erbB-2 protein. The effect of the MAbs on the anchorage-independent growth of erbB-2 transformed cells and on erbB-2 receptor turnover was also measured.

3T3 Cells↗

The nitrogen response of a barley C-hordein promoter is controlled by positive and negative regulation of the GCN4 and endosperm box.

The 431 bp C-hordein promoter of lambda-1-17 exhibits a specific response to amino acids and NH4NO3 in developing barley (Hordeum vulgare L.) endosperms. With the aid of particle bombardment it is shown that the GCN4 motif ATGA(C/G)TCAT is the dominating cis-acting element in this response. But synergistic interaction with the neighbouring endosperm motif TGTAAAGT within the bifactorial prolamin element and cooperation with upstream sequences including a second prolamin-like element is an absolute requirement for a strong, positive regulation by an optimal nitrogen regime. Low nitrogen levels convert the GCN4 box into a negative motif. In contrast the endosperm box on its own exerted a silencing activity, independent of nitrogen nutrition. Sequence comparisons revealed that GCN4- and endosperm-like motifs are widely distributed among plant promoters. Their putative role in nitrogen regulation is discussed.

Base Sequence↗

[Determination of endogenous N-excretion and nitrogen balance in the range of low N-intake in rats].

The investigations were carried out in order to develop foundations for a complex growth model including the effect of N-efficiency mechanism first of all for the rat. Therefore N-balance trials with rats of different live weights were made using diets of equal protein quality. The curve of the regressively calculated N-efficiency function courses relatively linear in its lower part, i.e. for low N-intakes. The protein quality value "A.b" was proved to be constant for all investigated live weight ranges. In similar trials with different protein qualities was also found a linear course for low N-intakes. The regressively estimated N-maintenance requirement (for N-Intake = 0) related to metabolic live weight (NMR/LWkg0.67) amounts to 180 mg/d. In addition endogenous N-excretions were determined in 15N tracer experiments on animals of different live weight fed graduated amounts of a quality constant protein. The NMR-values (sum of endogenous excretions from faeces and urea) depend on the level of N-intake, i.e. they can not be considered as constant. The endogenous faecal N-loss related to metabolic live weight is relatively constant indeed, whereas the amount of endogenous urea N-loss is dependent on the level of N-intake. Therefore calculations based on the N-efficiency curve, e.g. amino acid requirement dependent on performance and prediction of N-deposition respectively, should not be carried out on the basis of "N-retention" (N-balance + NMR) but only on the basis of N-balance.

Animals↗