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Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 127 records · Page 7Linked to original sources

[Huntington chorea. Animal models reveal new hypotheses for pathophysiology and therapy].

Huntington's disease (HD) is member of a growing family of neurodegenerative diseases which are caused by a CAG-Triplet expansion in the coding region of their respective genes. The results of the research of the last years is very suggestive of a common pathomechanisms of all these diseases even though their clinical appearance may be quite different. The development of new animal models by transferring the human gene defect into the mouse genome has led to the finding of so-called intranuclear inclusion bodies. This new observation allowed to come closer to solving the problem how this genetic defect causes neurodegeneration. Recent studies on transgenic HD mice could also demonstrate a possible connection between the genetic defect and glutamate exitotoxicity in the neurodegenerative process of HD which had been emphasized by earlier animal models of the disease. Transgenic animal models of HD will have an important impact on the understanding of the disease mechanisms and may contribute to a faster development and testing of new therapeutic approaches.

Animals↗

Spontaneous splenic rupture in infectious mononucleosis: conservative management with gradual percutaneous drainage of a subcapsular hematoma.

Spontaneous splenic rupture (SSR) is a rare but potentially lethal complication of infectious mononucleosis (IM). Because the inflamed spleen is usually enlarged, congested, and friable, emergency splenectomy is recommended. We describe the conservative management of a SSR in a 16-year-old boy with IM. A pigtail catheter was inserted under ultrasonographic guidance and left in place for 36 h. This allowed the successful evacuation of the hematoma without compromising the splenic parenchyma.

Adolescent↗

Simulator trials to determine the wear of the combination aluminium oxide ceramic-carbon fibre reinforced plastic (CFRP) used as an insert in a hip socket.

Hip simulator trials were conducted to determine the initial wear between alumina femoral heads and carbon fibre reinforced plastic (CFRP, CAPROMAN) insert in a titanium socket. A force of 2500 N and a frequency of 0.857 H were applied. Using surface and sphericity measurement techniques, the amount of wear was determined. After 500,000 cycles, the centre of the head had moved by 10 microm into the insert, and the average radius increased by 2 microm. After 1 million cycles, the additional changes were less than 1 microm. Based on an examination of retrieved implants (wear rate: 6.1 microm/year) and based on the simulator results, the combination alumina-CFRP inserts could be approved for total hip replacement.

Biomechanical Phenomena↗

Orthopedic and neurosurgical treatment of severe kyphosis in myelomeningocele.

Kyphosis in myelomeningocele is characterized by a complex pattern of problems during development and therapy. On the one hand, decompensation of upright posture leads to loss of sitting ability and social integration; on the other hand, accompanying malformations and trophic alterations threaten the physical integrity and performance. Neurologic function, cerebrospinal fluid (CSF) circulation, skeletal deformity and the urinary transport system need to be kept in mind and need to be treated with cooperation between the different specialties. Especially during serious surgical interventions such as spinal surgery, neither the nervous system nor the kidneys must be ignored. Sixteen patients underwent kyphectomy in the Orthopedic Department of the University of Mainz between 1993 and 1997, all of them supervised by the Neurosurgical Department. In 13 cases, transversal myelotomy was performed. No insufficiency of CSF circulation was seen; neither were there any CSF fistulae. Particular problems arose from the skin and soft tissue above the gibbus, the lack of muscles and the regeneration deficiency caused by trophic disorders. Therefore, a significantly higher complication rate was found than with other correctional operations.

Adolescent↗

Pax2/5 and Pax6 subdivide the early neural tube into three domains.

The nested expression patterns of the paired-box containing transcription factors Pax2/5 and Pax6 demarcate the midbrain and forebrain primordium at the neural plate stage. We demonstrate that, in Pax2/5 deficient mice, the mesencephalon/metencephalon primordium is completely missing, resulting in a fusion of the forebrain to the hindbrain. Morphologically, in the alar plate the deletion is characterized by the substitution of the tectum (dorsal midbrain) and cerebellum (dorsal metencephalon) by the caudal diencephalon and in the basal plate by the replacement of the midbrain tegmentum by the ventral metencephalon (pons). Molecularly, the loss of the tectum is demonstrated by an expanded expression of Pax6, (the molecular determinant of posterior commissure), and a rostral shift of the territory of expression of Gbx2 and Otp (markers for the pons), towards the caudal diencephalon. Our results suggest that an intact territory of expression of Pax2/5 in the neural plate, nested between the rostral and caudal territories of expression of Pax6, is necessary for defining the midbrain vesicle.

Animals↗

Inhibition of transforming growth factor beta1-induced hepatoma cell apoptosis by liver tumor promoters: characterization of primary signaling events and effects on CPP32-like caspase activity.

The effects of the liver tumor promoters phenobarbital, clofibrate, dieldrin, and DDT on transforming growth factor-beta1 (TGFbeta)-induced apoptosis were studied in FTO-2B hepatoma cells. Inhibition of apoptosis by these compounds was strongly correlated with a decrease in CPP32-like caspase activity. Similar effects were obtained with insulin and dexamethasone. CPP32-like activity may thus provide a useful tool for quantiation of apoptosis under various treatment conditions. Diverse effects on apoptosis-associated cellular signaling proteins were observed: insulin led to an activation of the MAP kinases ERK1/2, of PKB/Akt and of NF-kappaB, phenobarbital and clofibrate enhanced NF-kappaB activity solely, while dexamethasone slightly enhanced NF-kappaB activity and increased the expression of Bcl-xL. Since inhibition of apoptosis was still detectable if the anti-apoptotic compounds were administered more than 10 h after TGFbeta, the diverse primary signals appear to converge at a presumably late stage of apoptosis, but upstream of activation of CPP32 or related caspases.

Animals↗

[Ranking of 20 MHz sonography of malignant melanoma and pigmented lesions in routine diagnosis].

PURPOSE: Eleven dermatology clinics from all over Germany took part in our multicenter prospective study with the aim of evaluating 20 MHz sonography in the preoperative diagnosis of malignant melanomas and other pigmented skin tumours. It was to be assessed how effective sonographic measurement of thickness would compare to histology and the clinical palpation of tumour thickness and also the significance of differential diagnosis in sonography of malignant melanomas. METHOD: The prospective multicenter study proceed as follows. To the end of August 1997 264 patients with a primary malignant melanoma and 417 patients with benign skin tumours were examined via 20 MHz sonography. Two different examiners estimated the clinical thickness of the tumour by palpation. The tumour was then excised and examined for postoperative correlation with the histology sections. RESULTS: The final results showed good correlation between the histological and sonographic estimation of tumour thickness (r = 0.97). Estimation of tumour thickness by palpation showed no correlation with the histology (r = 0.59). Most of the benign (44%) and malignant tumours (38.7%) were spindle shaped. There was no significant difference between the benign and malignant tumour groups in relation to the sonographic presented shapes or echo signs. No different diagnosis could be made. CONCLUSION: The technique of high frequency sonography in relation to preoperative diagnosis of malignant melanomas has high priority. In contrast to clinical estimation of tumour thickness, sonography provided a good correlation to histology. The effectiveness of sonography with regard to the valence of the skin tumours is limited and there is no possibility of differentiating between malignant and benign tumours from the morphological face value. Hence, there is a demand for developing a 150 MHz apparatus which will be able to supply evidence regarding the valence of skin tumours.

Diagnostic Tests, Routine↗

The effect of connexin32 null mutation on hepatocarcinogenesis in different mouse strains.

Connexin32 (Cx32) is the major gap junctional protein in mouse liver. We have shown recently that the formation of liver tumours in Cx32-deficient mice is strongly increased in comparison with control wild-type mice, demonstrating that the deficiency in gap junctional communication has an enhancing effect on hepatocarcinogenesis. We have now compared the effect of Cx32 deficiency on liver carcinogenesis in two strains of mice with differing susceptibility to hepatocarcinogenesis. Heterozygous Cx32(+/-) females were crossed with male Cx32 wild-type C57BL/6J (low susceptibility) or C3H/He (high susceptibility) mice. Since the Cx32 gene is located on the X-chromosome, the resulting F1 males segregated to the genotypes Cx32(Y/+) and Cx32(Y/-). Genotyping was performed by PCR-analysis using tail-tip DNA. Weanling male mice were i.p. injected with a single dose of N-nitrosodiethylamine and were killed 16, 21 or 26 weeks later. The number, volume fraction and size distribution of precancerous liver lesions characterized by a deficiency in the marker enzyme glucose-6-phosphatase were quantitated. The results demonstrate that Cx32 deficiency only slightly affects the number of enzyme-altered lesions, but strongly enhances their growth, both in the resistant and the susceptible mouse strain, suggesting that decreased intercellular communication results in tumour promoting activity irrespective of the genetic background of the mouse strain used. Since Cx32-deficient C3H/He hybrids were approximately 5-10 times more sensitive than C3H/He hybrids with an intact Cx32 gene, this mouse strain may prove very useful for toxicological screening purposes.

Animals↗

Automatic acquisition of fiducial markers and alignment of images in tilt series for electron tomography.

Three-dimensional reconstruction of a section of biological tissue by electron tomography requires precise alignment of a series of two-dimensional images of the section made at numerous successive tilt angles. Gold beads on or in the section serve as fiducial markers. A scheme is described that automatically detects the position of these markers and indexes them from image to image. The resulting set of position vectors are arranged in a matrix representation of the tilt geometry and, by inversion, alignment information is obtained. The scheme is convenient, requires little operator time and provides an accuracy of < 2 pixels RMS. A tilt series of 60-70 images can be aligned in approximately 30 min on any modern desktop computer.

Algorithms↗

Evidence for a non-orthostatic origin of orthostatic tremor.

OBJECTIVES: Orthostatic tremor was first described by Heilman in 1984. It usually occurs in the legs during stance and decreases markedly during sitting or walking. The aim of this study was to determine if orthostatic tremor is invariably associated with the orthostatic and weight bearing conditions in the arms and legs, and to investigate the features of orthostatic tremor under different levels of peripheral loading. METHODS: Multichannel surface EMG recordings were obtained under different conditions (body posture and peripheral loading) from the proximal arm and leg muscles of seven patients fulfilling the clinical and electrophysiological criteria of orthostatic tremor. RESULTS: In weight bearing positions (stance; weight bearing on the hands on all fours), all patients showed 13 Hz-16 Hz tremor activity, predominantly in the active limb. No tremor activity could be found in a supine position with muscles at rest. Isometric contraction of the limbs in the supine position led to synchronous 13 Hz-16 Hz rhythmic activity in five patients. No tremor was seen when the subjects were suspended in a harness with relaxed legs. Isometric contraction of the legs in this position produced tremor in two patients. A stepwise reduction of the body weight by a harness reduced the tremor activity. Additional loading (10 kg-20 kg) during stance led to an increase in tremor amplitude, but tremor frequency remained unchanged. CONCLUSIONS: Orthostatic tremor is invariably present during stance or other weight bearing positions. It is not, however, always associated with orthostasis. In at least some patients it can be classified as an orthostasis independent action tremor. The failure of peripheral loading to modify tremor frequency indicates that orthostatic tremor may have a central, rather than a peripheral, origin.

Aged↗

EMAP II: a modulator of neovascularization in the developing lung.

Neovascularization is a key regulatory process in fetal growth and development. Although factors promoting growth and development of the pulmonary vasculature have been investigated, nothing is known regarding the molecular mechanisms that may counteract these stimuli. Endothelial monocyte-activating polypeptide (EMAP) II has recently been identified as an antiangiogenic factor in tumor vascular development. We postulated that EMAP II is a putative negative modulator of lung vascular growth. EMAP II mRNA and protein decrease fivefold (P < 0.01) as the developing lungs in the fetal mouse progress from having poor vascularization (day 14) to having complete vascular development at term (day 18.5). EMAP II protein expression continues to remain low throughout postnatal life and into adulthood, with the exception of a surge that correlates with microvascular maturation. Furthermore, through the use of in situ hybridization and immunohistochemistry, EMAP II is localized throughout the lung, with significant expression in the submyoepithelial area during the early stages of lung development when there is minimal vascular development. In contrast, EMAP II is distributed around the large vessels during the end of vascular development, suggesting that EMAP II modulates the neovascularization process. We speculate that EMAP II is a director of neovascularization in the developing lung.

Animals↗

[Primary stability of cement-free press-fit acetabulum cups. In vitro displacement studies].

The initial stability of 6 different hemispherical press-fit titanium acetabular cups was investigated by lever-out tests using a foam model. Each cup was implanted in a standardised manner into machined PVC-foam blocks with an underreaming of 1/2/3 mm, and levered out 5 times. A computer recorded the load-displacement curves. Both insertion forces and lever-out forces increased with increasing press-fit from 1 to 2 mm. With underreaming of 2 mm, insertion forces varied between 9 and 34 Nm, and lever-out torques between 13 and 23 Nm. The cup made up of multi-layer irregular titanium wire mesh had the highest initial stability of all the cups tested. 3 mm underreaming was associated with insertion difficulties, so that lever-out is difficult to compare with that with 1 and 2 mm. The amount of contact on the equatorial rim, where we saw the most attrition after lever-out, is the most important factor for determining the lever-out torque. The quality of the PVC foam blocks, the accuracy of reaming, and the definition of cup insertion are very important parameters for test reproduction. Since the trials were conducted under laboratory conditions, translation of the results to the intraoperative situation should be undertaken only with certain reservations.

Acetabulum↗