Biomedical subjects
Publications and source records attributed to S Kaiser.
We report the case of a girl with known large right-sided and small left-sided neonatal adrenal haematomas who underwent bone scintigraphy 23 days after birth for suspected osteomyelitis. The radionuclide examination showed uptake of bone tracer around the right-sided haematoma, but no abnormality on the left side.
Potential effects of tamoxifen therapy on blood coagulation and fibrinolysis were investigated in women with breast cancer. We studied 14 parameters of hemostasis in 19 postmenopausal women receiving 20 mg tamoxifen/day as an adjuvant treatment. Blood sampling was done before and after the 1st, 3rd, and 6th month of treatment. Pretreatment values of procoagulation, anticoagulation, plasminogen, and plasminogen activator inhibitor were found within the reference range, whereas tissue-plasminogen activator, fibrin degradation products, and prothrombin-fragment 1+2 were elevated. On therapy an initial decrease of all measured parameters was observed. The effect was pronounced in coagulation inhibitors (antithrombin III, protein C and S). No pathological values (below 60%) were observed. No further effects were found during the 3rd and 6th month of treatment. Our data indicate that the decrease of hemostatic parameters during the initial phase of tamoxifen treatment is due to the timing of blood collection, which took place no more than 14 days after surgery. The reduction of coagulation inhibitors was not associated with pathological values. No cumulative effects were seen during tamoxifen therapy. The decrease was not associated with a concomittant increase of in vivo coagulation markers (prothrombin-fragment 1+2, thrombin-antithrombin-complex, fibrin degradation products). Therefore our results are likely to reflect only the resolution of postoperative activation and do not translate into a drug related thrombogenic effect.
Growth factors of the transforming growth factor-beta superfamily are involved in cutaneous wound healing. In this study we analyze the expression of the bone morphogenetic protein-6 (BMP-6) gene, a transforming growth factor-beta related gene, in skin wounds. In normal mouse skin high levels of BMP-6 mRNA and protein are expressed by postmitotic keratinocytes of stratified epidermis until day 6 after birth. BMP-6 expression is strongly reduced in adult epidermis with diminished mitotic activity. After skin injury we found large induction of BMP-6-specific RNA and protein in keratinocytes at the wound edge and keratinocytes of the newly formed epithelium as well as in fibroblast shaped cells in the wound bed. BMP-6-specific RNA was induced within 24 h after injury, whereas significant upregulation of BMP-6 on the protein level was detected only 2-3 d after injury. Protein was confined to outermost suprabasal epidermal layers, whereas BMP-6-specific RNA was distributed throughout all epidermal layers including basal keratinocytes and the leading edge of the migrating keratinocytes. We also detected high levels of BMP-6-specific RNA and protein in chronic human wounds of different etiology. In contrast to the overall distribution pattern of BMP-6-specific RNA, the protein was not detected in keratinocytes directly bordering the wound. In order to test the influence of BMP-6 abundance on the progress of wound healing, we analyzed the wound response of transgenic mice overexpressing BMP-6 in the epidermis. In these mice, reepitheliazation of skin wounds was significantly delayed, suggesting that strict spatial and temporal regulation of BMP-6 expression is necessary not only for formation but also for reestablishment of a fully differentiated epidermis.
PURPOSE: The traditional approach to investigating suspected osteomyelitis in children includes conventional radiography and bone scintigraphy. The roles of US, CT and MR imaging are controversial. Our objective was to determine whether the additional use of these modalities would yield information likely to lead to treatment modification. MATERIAL AND METHODS: Sixty-five children with clinically suspected osteomyelitis took part in a prospective study. All patients underwent conventional radiography and bone scintigraphy. In addition to this, US, CT and MR imaging were all performed in 33 patients; the remaining 32 patients were examined with various combinations of these three modalities. The value of the additional information obtained was estimated retrospectively by a pediatric orthopedic surgeon in terms of possible modification of treatment. RESULTS: MR imaging was the modality with the highest sensitivity and specificity for detecting osteomyelitis. MR yielded information likely to influence treatment in the greatest proportion of patients (45%) followed by US (30%). CONCLUSION: The standard investigation protocol with the addition of US (because of its ability to detect subperiosteal abscesses early and simply) is adequate in uncomplicated cases. When additional imaging is required to outline a lesion, or in complicated cases, and when bone scintigraphy is inconclusive, MR imaging should also be performed. CT should be considered when MR investigation is not available or when anesthesia is required but cannot be provided.
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Hypertonic-induced cell shrinkage increases glucose release in H-4-II-E rat hepatoma cells. This is paralleled by a concomitant increase in the mRNA levels of the rate-limiting enzymes of the pathway of gluconeogenesis, phosphoenolpyruvate carboxykinase (PCK) and fructose-1,6-bisphosphatase (FBP), of seven- and fivefold, respectively. In contrast, hypotonic-induced swelling of the cells results in a transient decrease in PCK and FBP mRNAs to 15% and 39% of control levels. The antagonistic effects of hyper- and hypotonicity mimic the counteracting effects of adenosine 3',5'-cyclic monophosphate (cAMP) and insulin on PCK and FBP mRNA levels. The hypertonic-induced increase in mRNA levels is due to an enhanced transcriptional rate, whereas the decrease in mRNAs caused by hypotonicity results from a decrease in transcription as well as mRNA stability. The inductive effect of hypertonicity does not require ongoing protein synthesis and acts independently of the cAMP-dependent protein kinase and protein kinase C pathways. These results suggest that cell volume changes in liver cells may play an important role in regulating hepatic glucose metabolism by altered gene expression.
We proposed that the alpha2-Heremans Schmid glycoprotein/fetuin family of serum proteins inhibits unwanted mineralization. To test this hypothesis in animals, we cloned the mouse fetuin gene and generated mice lacking fetuin. The gene consists of seven exons and six introns. The cystatin-like domains D1 and D2 of mouse fetuin are encoded by three exons each, whereas a single terminal exon encodes the carboxyl-terminal domain D3. The promoter structure is well conserved between rat and mouse fetuin genes within the regions shown to bind transcription factors in the rat system. Expression studies demonstrated that mice homozygous for the gene deletion lacked fetuin protein and that mice heterozygous for the null mutation produced roughly half the amount of fetuin protein produced by wild-type mice. Fetuin-deficient mice were fertile and showed no gross anatomical abnormalities. However, the serum inhibition of apatite formation was compromised in these mice as well as in heterozygotes. In addition, some homozygous fetuin-deficient female ex-breeders developed ectopic microcalcifications in soft tissues. These results corroborate a role for fetuin in serum calcium homeostasis. The fact that generalized ectopic calcification did not occur in fetuin-deficient mice proves that additional inhibitors of phase separation exist in serum.
Warm ischemia is known to induce substantial damage to the liver parenchyma. With respect to clinical liver transplantation, the tolerance of the liver to warm ischemia and the preservation of these organs have not been studied in detail. In isolated reperfused pig livers we proceeded according to the following concept: Livers were subjected to 1 or 3 h of warm ischemia. Subsequently, these organs were preserved by either normothermic perfusion or cold storage (histidine-tryptophan-alpha-ketoglutarate, HTK) for 3 h each. After storage, liver function was assessed in a reperfusion circuit for another 3 h. Parameters under evaluation were bile flow, perfusion flow, oxygen consumption, enzyme release into the perfusate (creatine kinase, glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase, and glutamic pyruvic transaminase), and histomorphology. Damage to the liver was lowest after warm ischemia of 1 h. The results after cold storage were superior to those after normothermic perfusion (GOT: 3.2 +/- 0.3 and 2.6 +/- 0.2 U/g liver; cumulative bile production: 14.7 +/- 2.1 and 9.4 +/- 1 ml, respectively; P < 0.05). In contrast, we found substantial damage at the end of reperfusion in livers undergoing 3 h of warm ischemia under both preservation techniques with severe hepatocellular pyknoses and essentially altered nonparenchymal cells. The results suggest that pig livers undergoing 1 h of warm ischemia and cold storage for 3 h with HTK solution may lead to functioning after transplantation.
Experiments are described concerning the differences in redox properties and biodurability of natural asbestos fibres and an experimental stonewool fibre incubated in Gamble solution and reconstructed surfactant fluid. Crocidolite exhibits a significantly higher oxidative potential compared to the tested stonewool fibres. The oxidative activity of both types of fibres is not constant during incubation over several weeks, but rather shows a sinoidal curve including reactivities much higher than those at the beginning of the incubation. A continuous loss of mass is concluded not to be definitively connected with a continuous loss of toxicity.
Specifications about the size of healthy salivary glands are not available to date. Therefore, we determined the size of the submandibular and the parotid glands by ultrasonography in 50 subjects (25 men, 25 women, mean age 45 y, range 20-68) with no history of disease affecting the salivary glands. The subjects were equally distributed concerning gender and age. Body weight did not differ more than 20% from the ideal weight following Broca's formula (mean body weight 71 kg, range 46-95 kg). In the submandibular glands we found an anterior-posterior length of 35 mm +/- 5.7 mm, a paramandibular dimension to the depth of 14.3 mm +/- 2.9 mm and a dimension in frontal scanning of 33.7 mm +/- 5.4 mm. The parotid glands were measured 46.3 mm +/- 7.7 mm in the axis parallel to the mandibular ramus and 37.4 mm +/- 5.6 mm in the transversel axis. The dimension of the parotid parenchyma was measured with 7.4 mm +/- 1.7 mm lateral to the mandible and 22.8 mm +/- 3.6 mm dorsal to the mandible. No statistically significant difference to the 5%-level was found concerning gender. The dimension of the parotid glands correlated statistically significantly with body weight (p = 0.03). This correlation was not found in the dimension of the submandibular glands. Age did not correlate with the dimension of salivary glands. Results of the submandibular glands were compared with volume measurements of submandibular glands from cadavers.
Noise in EEG and MEG measurements leads to inaccurate localizations of the sources. A confidence volume is used to describe the amount of localization error. Previous methods to estimate the confidence volume proved insufficient. Thus a new procedure was introduced and compared with previous ones. As one procedure, Monte Carlo simulations (MCS) were performed. The confidence volume was also estimated using two methods with different assumptions about a linear transfer function between source location and the distribution of the potential. One method used variable (LVM) and the other fixed dipole orientations (LFM). Finally, the confidence volume was estimated through a procedure in which there was no linearization of the transfer function. This procedure scans the confidence volume by varying the dipole location in multiple directions. Confidence volumes were calculated for simulated distributions of the electrical potential and for experimental data including somatosensory evoked responses to stimulation of lower lip, thumb, and little finger. Results from simulated data indicated that confidence volumes calculated with the MCS method were largest, and those calculated with the LFM method were smallest. For dipole locations close to the brain surface, the confidence volume was smaller than for a central deeper source. An increase in electrode density resulted in smaller confidence volumes. When the noise was correlated, only the method using the MCS produced acceptable results. Since the noise in experimental data is highly correlated, only the MCS method would appear to be useful in estimating the size of the confidence volume of the dipole locations. Thus, using real data with the MCS method, we easily distinguished separate and distinct representations of the thumb, little finger, and lower lip in the somatosensory cortex (SI). It was concluded that adequate estimation of confidence volumes is useful for localizing neural activity. On a practical level, this information can be used prior to an experiment for determining the conditions necessary to distinguish between different dipole sources, including the required signal to noise ratio and the minimum electrode density.
Both cell proliferation and apoptosis (programmed cell death) are supposed to play a role in restenosis after angioplasty. We studied these processes in smooth muscle cells (SMCs) and macrophages 1, 4, and 12 weeks after balloon angioplasty or Palmaz-Schatz stent implantation in rabbit iliac arteries. Proliferating cells were visualized by immunostaining with antibodies directed against proliferating cell nuclear antigen. Apoptotic cells were detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) technique, propidium iodide staining, and transmission electron microscopy. At all time points, the neointimal cross-sectional area of the arteries was twofold to fourfold greater after stent implantation than after balloon angioplasty. The total number of neointimal cells was similar 1 and 12 weeks after both interventions. The neointimal cell density, however, decreased by 58% between the 1st and the 12th week after stent implantation compared with a 20% decrease after balloon angioplasty (P < .01). Stent implantation induced more cell proliferation but also more apoptosis in the media than balloon angioplasty after 1 and 4 weeks. In addition, stent implantation caused more macrophage accumulation and apoptosis in the neointima, but cell proliferation rates did not differ significantly in comparison with balloon angioplasty. The higher rate of apoptosis in the neointima 1 week after stent implantation compared with balloon angioplasty is due to an increased rate of SMC and macrophage death. Macrophage accumulation and apoptosis in the early phase after stent implantation appear to play a role in extracellular matrix secretion, which increases neointima formation after 4 and 12 weeks compared with balloon angioplasty in this model.
Diet-derived lipids may influence cytokine-mediated endothelial cell dysfunction, including TNF-induced apoptosis. To test this hypothesis, oxidative stress, intracellular calcium levels, endothelial barrier function, cell viability, and apoptosis were measured in vascular endothelial cells treated with 90 microM linoleic acid (18:2, n-6) and/or 20 ng/mL TNF (100 U/mL). For short-term exposure, endothelial cells were exposed to 18:2 for 6 h or to TNF for 1.5 h. For long-term exposure, endothelial cultures were treated with 18:2 for 24 h and with TNF for 19.5 h. In cells exposed to 18:2 + TNF, pretreatment with 18:2 began 4.5 h before additional exposure to TNF for either 1.5 h (short-term exposure) or 19.5 h (long-term exposure). After treatment, endothelial cultures were washed and incubated with maintenance medium for up to 4 days. Although initial treatment with TNF or 18:2 significantly increased oxidative stress and intracellular calcium levels, only exposure to TNF induced apoptosis in cultured endothelial cells. Furthermore, the combined exposure to 18:2 + TNF potentiated TNF-induced apoptosis. Additional treatments with BAPTA-AM, n-propyl gallate, vitamin E, and with aurintricarboxylic acid partially protected against TNF- or 18:2 + TNF-induced apoptosis. The present study suggests that changes in the cellular lipid environment may markedly influence local TNF-induced events in the vascular endothelium, including endothelial cell apoptosis. Such mechanisms may play a role in the damage and death of vascular endothelial cells in atherosclerosis.
In this article we summarize our work on the relationships between the social environment, behaviour and stress in guinea pigs. We confirm what Jim Henry predicted to be a general rule for all mammals including man 20 years ago: The individual's degree of social stress is related to the stability of the pre- and postnatal social environment in which it lives, to the amount of social support which it receives from bonding partners and to the social experiences which it has made during behavioural development.
Stopped flow measurements to determine the permeability of vesicles are presented. The kinetics of the reaction between FeSCN2+ and F- ions is used to monitor the permeability of vesicles. Samples with vesicles that have been equilibrated with the iron complex are mixed with F- solutions. The reaction is followed by UV/VIS absorption. The influence of temperature and surfactant concentration on the membrane permeability of large unilamellar phospholipid vesicles was studied. A dramatic increase of the permeability of the LUVs is observed when 30 to 40 mol% of the surfactant OP-10 (main component of Triton X-100) is added to the lipid. It is assumed that the increased permeability is due to the stabilization of transient defects in the bilayers of the vesicles as shown previously by other groups. Furthermore, a strong binding of the iron (III) thiocyanate complex to the phospholipid is observed by UV/VIS spectroscopy and zeta-potential measurements. Additional experiments with vesicles from a fluorocarbon surfactant show a much higher permeability than the phospholipid system. Models for the diffusion of either the iron (III) complex or the fluoride ions through the vesicles bilayer are discussed for LUV as well as for vesicles from a fluorocarbon surfactant. The results indicate that the rate-determining step is the diffusion of the iron complex through the membrane.
The interval between the onset of symptoms in patients with head and neck cancers and the introduction of treatment was evaluated. During a 1-year period, patients were interviewed to determine the duration of any delays from the onset of complaints until the first visit to a doctor. Also asked was how long it took to be referred to an ENT specialist and actual referral to our department. We then determined the interval from diagnosis to the introduction of therapy. It was found that the delay of patients who went directly to an otorhino-laryngologist was shorter (median, 8 weeks) than that of patients who first went to their family doctors (median, 13 weeks) (P < 0.02). The latter then took an additional 4 weeks before sending patients to an otorhinolaryngologist. Referral from the ENT specialist to our department took another 2 weeks, as well as our staging and pre-therapeutic management. Our findings show that the patient himself is the critical factor in delaying diagnosis and therapy. Tumor patients with greater professional qualification went to their doctors earlier (P < 0.0001) or more often went directly to an ENT specialist (P < 0.002). Consultations of physicians without experience in otorhinolaryngology caused yet further delays.
This study investigated the influence of the social environment during pregnancy and lactation on the female offsprings' behaviour and body weight. The subjects studied were daughters whose mothers had lived: a) in a stable social environment (SSE) during pregnancy and lactation; b) in an unstable social environment (USE) during pregnancy and lactation; c) in a SSE during pregnancy but in an USE during lactation; d) in an USE during pregnancy but in a SSE during lactation. The SSE was made by keeping the group composition (one male, five females) constant; in the USE situation every third day two females from different groups were exchanged. After weaning (n = 4 x 3 = 12), groups of daughters, consisting of four females each, were established, originating from the different categories of mothers. From their 41st through their 80th day of age the spontaneous behaviour of the daughters was recorded in their home cages. When the mothers had lived in an USE during pregnancy, the daughters displayed significantly higher amounts of male-typical courtship, play, and social orientation behaviour compared to daughters whose mothers had lived in a SSE during pregnancy. The stability and instability, respectively, of the social environment during lactation, however, had no significant influence on the daughters' prospective behaviour. The four categories of daughters did not differ in their body weights either at birth or at 80 days of age. Thus, the instability of the social environment during pregnancy obviously represented a mild stressor that nevertheless caused a distinct masculinization of the daughters' behaviour.
Bone morphogenetic protein-6 (BMP-6) belongs to the family of TGF-beta-related growth factors. In the developing epidermis, expression of BMP-6 coincides with the onset of stratification. Expression persists perinatally but declines after day 6 postpartum, although it can still be detected in adult skin by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. We constitutively overexpressed BMP-6 in suprabasal layers of interfollicular epidermis in transgenic mice using a keratin 10 promoter. All mice expressing the transgene developed abnormalities in the skin, indicating an active transgene-derived factor. Depending on the pattern of transgene expression, the effects on proliferation and differentiation were completely opposite. Strong and uniform expression of the BMP-6 transgene resulted in severe repression of cell proliferation in embryonic and perinatal epidermis but had marginal effects on differentiation. Weaker and patchy expression of the transgene evoked strong hyperproliferation and parakeratosis in adult epidermis and severe perturbations of the usual pattern of differentiation. These perturbations included changes in the expression of keratins and integrins. Together with an inflammatory infiltrate both in the dermis and in the epidermis, these aspects present all typical histological and biochemical hallmarks of a human skin disease: psoriasis.