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Biomedical subjects

P Huber

Publications and source records attributed to P Huber.

At least 73 records · Page 4Linked to original sources

Neutron therapy in malignant salivary gland tumors: results at European centers.

Malignant salivary gland tumors are relatively rare and account for only 3%-4% of all head and neck cancers. Especially in adenoid cystic carcinoma, the incidence of local recurrence and distant metastases is influenced by the perineural spread of tumor. In advanced salivary gland tumors, surgery alone has a high incidence of local failure. The results of conventional radiotherapy are suboptimal in inoperable or not completely resected salivary gland tumors and in recurrent disease. The pooled data of some international series for low linear energy transfer radiation show a local control of only 28%. Especially in advanced salivary gland tumors, neutron therapy can improve local control. In Europe at least 570 patients with salivary gland tumors have been treated with neutrons alone or with combined modalities. The clinical data of different centers in Europe and the United States result in a similar local control rate of 67% in gross disease. An analysis of different European series shows on average a complication rate of 10.6% for severe radiation-related morbidity. Modern neutron machines and the use of three-dimensional treatment planning systems are now available in a few institutions and may further reduce side effects.

Aged↗

Growth characteristics of fowl adenovirus type 8 in a chicken hepatoma cell line.

Fowl adenoviruses, many of which appear to be non-pathogenic, are ubiquitous in birds. In addition, the genome of these viruses is large, making them ideal candidates for construction as vectors for foreign genes. Current methods to cultivate fowl adenoviruses use primary cell cultures derived from embryonated chicken eggs. In order to provide a more suitable culture method, the growth of fowl adenovirus type 8 (FAdV-8) was investigated in CH-SAH, a continuous hepatoma cell line. A one step growth curve demonstrated release of extracellular virus beginning by 18 h p.i. and with a final yield about 100 fold higher than that in chicken embryo liver cells. Viral DNA synthesis was first detected 8 h prior to this. The CH-SAH cell line supported the production of progeny viruses similar to the wild-type virus after being transfected with purified FAdV-8 DNA. This study demonstrated that the continuous hepatoma cell line is an appropriate in vitro host for FAdV-8.

Animals↗

Influence of shock wave pressure amplitude and pulse repetition frequency on the lifespan, size and number of transient cavities in the field of an electromagnetic lithotripter.

Monitoring the generation of cavitation is of great interest for diagnostic and therapeutic use of ultrasound in medicine, since cavitation is considered to play a major role in nonthermal ultrasound interactions with tissue. Important parameters are the number of cavitation events and the energy released during the bubble collapse. This energy is correlated to the maximum bubble radius which is related to the cavitation lifespan. The aim of this study was therefore to investigate the influence of the acoustic pressure amplitude and the pulse repetition frequency (PRF) in the field of a lithotripter (Lithostar, Siemens) on the number, size and lifespan of transient cavitation bubbles in water. We used scattered laser light recorded by a photodiode and stroboscopic photographs to monitor the cavitation activity. We found that PRF (range 0.5-5 Hz) had no influence on the cavitation bubble lifespan and size, whereas lifespan and size increased with the acoustic pressure amplitude. In contrast, the number of cavitation events strongly increased with PRF, whereas the pressure amplitude had no significant influence on the number of cavitation events. Thus, by varying the pressure amplitude and PRF, it might be possible to deliver a defined relative number of cavitations at a defined relative energy level in a defined volume. This seems to be relevant to further studies that address the biological effects of transient cavitation occurring in the fields of lithotripters.

Electric Conductivity↗

Percutaneous electrical nerve stimulation (PENS): a complementary therapy for the management of pain secondary to bony metastasis.

OBJECTIVE: To evaluate the use of a novel nonpharmacologic analgesic therapy known as percutaneous electrical nerve stimulation (PENS) in the management of opioid-resistant cancer pain. DESIGN: PENS therapy was administered to three cancer patients on three or more occasion using acupuncturelike needle probes that were stimulated for 30 minutes at frequencies of 4-100 Hz. RESULTS: Two of the three patients achieved good to excellent pain relief that lasted 24-72 hours after each treatment session. CONCLUSION: PENS therapy is a useful supplement to opioid analgesics for the management of pain secondary to bony metastasis in terminal cancer patients.

Aged↗

Structural interactions between actin, tropomyosin, caldesmon and calcium binding protein and the regulation of smooth muscle thin filaments.

The basic structure and functional properties of smooth muscle thin filaments were established about 10 years ago. Since then we and others have been working on the details of how tropomyosin, caldesmon and the Ca(2+)-binding protein regulate actin interaction with myosin. Our work has tended to emphasize the similarities between caldesmon and troponin function whilst others have been more concerned with the differences. The need to resolve the resulting differences has stimulated us to find new and more direct ways of investigating the mechanism of thin filament regulation. In recent years an apparent divergence has opened up between functional measurements, which indicate an allosteric-cooperative regulatory mechanism in which caldesmon and Ca(2+)-binding protein control actin-tropomyosin state in the same way as troponin, and structural measurements which show thin filament structures unlike striated muscle thin filaments. The challenge is to interpret function in terms of structure. We have combined functional studies with expression and mutagenesis of caldesmon and with structural methods including X-ray crystalography of tropomyosin-caldesmon crystals, electron microscopy and helical reconstruction of actin-tropomyosin-caldesmon complexes and high resolution nuclear magnetic resonance spectroscopy of the C-terminus of caldesmon in interaction with actin and calmodulin. We have used this information to propose a structural mechanism for caldesmon regulation of the smooth muscle thin filament.

Actins↗

Assessment of the subclavian vein in patients with transvenous pacemaker leads.

Thrombosis of the subclavian vein can occur after the implantation of transvenous pacemaker electrodes. Although this is seldom followed by thromboembolic complications, it can cause problems when replacing the leads. To assess the impact of the pacemaker leads on the subclavian vein, a study using noninvasive duplex sonography was performed on 56 patients at an average of 41 months after the implantation. Forty-three percent of the patients were found to have a normal function of the subclavian vein, 46% developed pathological changes of the vessel wall, and 11% occluded. These changes rarely caused symptoms, and, therefore, had little clinical significance. Moreover, the occlusion rate was found independent of the patient's age, the patient's sex, the number of electrodes, the procedure of implantation, and even the time from implantation. As a result, the clinical diagnosis of occlusion is uncertain. Therefore, duplex sonography is recommended as an easy means of excluding a totally thrombosed subclavian vein prior to replacing pacemaker leads.

Aged↗

Targeted null-mutation in the vascular endothelial-cadherin gene impairs the organization of vascular-like structures in embryoid bodies.

Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed in endothelial cells and is strictly located at cell-to-cell junctions. As the other members of the cadherin family, VE-cadherin is able to mediate a homotypic type of cellular interaction in a Ca2+-dependent manner. In the mouse embryo, VE-cadherin transcripts are detected at the earliest stages of vascular development. To ascertain if VE-cadherin expression is required for the assembly of endothelial cells into vascular structures, we generated VE-cadherin-negative mouse embryonic stem cells (VE-cadherin-/- ES cells) by gene targeting and examined the consequences on vascular development of ES-derived embryoid bodies (EBs). In contrast to wild-type EBs, we observed that endothelial cells remained dispersed and failed to organize a vessel-like pattern in VE-cadherin-/- ES-derived EBs. However, dispersed VE-cadherin-/- ES-derived endothelial cells expressed a large range of other endothelial markers. Moreover, the targeted null-mutation in the VE-cadherin locus did not interfere with the hematopoietic differentiation potential of ES cells. These in vitro experiments are consistent with a pivotal role of VE-cadherin in vascular structure assembly.

Animals↗

Genomic structure and chromosomal mapping of the mouse VE-cadherin gene (Cdh5).

Vascular endothelial cadherin (VE-cadherin) is located strictly at endothelial junctions and appears to be a major adhesive component of cell to cell contacts. Genomic clones spanning 36 kb and encompassing the mouse VE-cadherin gene have been isolated and characterized. The gene is composed of 12 exons that exhibit conventional vertebrate splicing. The first exon is entirely untranslated, and both exons 2 and 12 contain untranslated regions. A single major transcriptional start site was identified and located 75 bases upstream of the translation initiation codon in the cDNA sequence. The proximal 5'-flanking domain lacks consensus TATA and CAAT boxes at the usual positions. Exon-intron boundaries are similar to those of other cadherin genes, with some exceptions that may have a functional significance in VE-cadherin behavior. The VE-cadherin gene (locus Cdh5) maps to mouse chromosome 8, where it colocalizes with E-cadherin (locus Cdh1), P-cadherin (locus Cdh3), and M-cadherin (locus Cdh14) genes, suggesting that it might be part of a larger cluster of cadherin sequences.

Amino Acid Sequence↗

[Therapeutic ultrasound in tumor therapy. Principles, applications and new developments].

We are interested in the interaction of high-energy ultrasound with biological tissue with regard to cancer therapy. The physical and biological aspects of this are reviewed and summarized in this paper. The preliminary results give reason to hope, as ultrasound is easy to focus [correction of focuse] and might be applicable as a supplementary therapeutic technique in ultrasound-accessible tumors. The changes observed in biological studies are clearly a function of the physical parameters. Therefore, it is possible to calculate and predict the biological effects. Recent results have shown the potential of magnetic resonance imaging in monitoring ultrasound therapy online. The capability of MRI to measure temperature will be an important tool for the safe and reliable application of this new therapeutic approach. The role of ultrasound therapy in the management of human tumors must be clarified in carefully conducted clinical trials.

Body Temperature Regulation↗

A new method of quantitative cavitation assessment in the field of a lithotripter.

Transient cavitation seems to be a very important effect regarding the interaction of pulsed high-energy ultrasound with biologic tissues. Using a newly developed laser optical system we are able to determine the life-span of transient cavities (relative error less than +/- 5%) in the focal region of a lithotripter (Lithostar, Siemens). The laser scattering method is based on the detection of scattered laser light reflected during a bubble's life. This method requires no sort of sensor material in the pathway of the sound field. Thus, the method avoids any interference with bubble dynamics during the measurement. The knowledge of the time of bubble decay allows conclusions to be reached on the destructive power of the cavities. By combining the results of life-span measurements with the maximum bubble radius using stroboscopic photographs we found that the measured time of bubble decay and the predicted time using Rayleigh's law only differs by about 13% even in the case of complex bubble fields. It can be shown that the laser scattering method is feasible to assess cavitation events quantitatively. Moreover, it will enable us to compare different medical ultrasound sources that have the capability to generate cavitation.

High-Energy Shock Waves↗

European results in neutron therapy of malignant salivary gland tumors.

In Europe to date, 501 patients with salivary gland tumors have been treated with neutrons alone or with combined modalities. The most common histological types are adenoid cystic carcinomas, mucoepidermoid carcinomas and malignant mixed tumors. The results of conventional radiotherapy are suboptimal in inoperable or incompletely resected salivary gland tumors and in recurrent disease. The pooled data of some international series for low linear energy transfer radiation show a local control of 28%. Especially in advanced tumors neutron therapy can improve local control and should be the treatment of choice. The clinical data from different therapy centers in Europe show local control of 67% in gross disease.

Carcinoma, Adenoid Cystic↗

[Patient transfer between 2 hospital services: informing patients].

In order to determine what inpatients transferred to another inpatient care facility know about their health problems, the motives for their transfer, and the level of agreement between patients and physicians on these issues, we conducted a semi-structured interview and a content analysis of the transfer letter of 64 consecutive patients transferred from an academic internal medicine unit to a related intermediate care internal medicine unit with a vocation of rehabilitation and psychosocial care. After a mean length of stay of 18.5 +/- 11 days, 31% of patients did not know their medical diagnosis and only 54% knew at least one motive of transfer they agreed with. Only 48.5% of patients described a motive of transfer which was also found in their transfer letter. Doctors and patients disagreed on a psychosocial motive for transfer for 15.5% of patients. 14% of patients were opposed to their transfer and 7% did not know why they were transfered. Finally 22% of transfer letters were not informative enough to allow comparison. We conclude that at the time of their transfer a large number of patients lack adequate information on their diagnosis and on the reasons for their transfer.

Aged↗

Impaired action of thyroid hormone associated with smoking in women with hypothyroidism.

BACKGROUND: The effect of smoking on thyroid function is controversial, and its effect on thyroid hormone action is unknown. We investigated the effects of cigarette smoking in women with various grades of hypothyroidism and in normal women. METHODS: We studied 138 normal women and 135 women with primary hypothyroidism, of whom 84 had subclinical hypothyroidism and 51 overt hypothyroidism. Sixty of the women with hypothyroidism were reevaluated during thyroxine therapy. The women were categorized as smokers or nonsmokers according to their responses to a questionnaire. Thyroid function was evaluated by measurements of serum thyrotropin, free thyroxine, and triiodothyronine. Peripheral thyroid hormone action was assessed by a clinical score and measurements of ankle-reflex time and serum lipids and creatine kinase. RESULTS: Among the women with subclinical hypothyroidism, the smokers had a higher mean (+/- SD) serum thyrotropin concentration (21.3 +/- 16.6 vs. 12.7 +/- 7.2 mU per liter, P = 0.004) and a higher ratio of serum triiodothyronine to serum free thyroxine (by 30 percent, P = 0.003) than the nonsmokers. Their serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol were higher (by 16 percent, P = 0.013; and 28 percent, P = 0.003, respectively). Among the women with overt hypothyroidism, the serum concentrations of thyrotropin, free thyroxine, and triiodothyronine were similar in the smokers and nonsmokers. As compared with the nonsmokers, the smokers had a clinical score indicating a greater degree of hypothyroidism (P < 0.001), higher serum concentrations of total and LDL cholesterol (by 25 percent, P < 0.001; and 24 percent, P = 0.002, respectively), longer ankle-reflex time (by 25 percent, P < 0.001), and higher serum concentrations of creatine kinase (by 236 percent, P < 0.001). There were dose-response relations between smoking and serum concentrations of total and LDL cholesterol, serum creatine kinase concentrations, and ankle-reflex time in the women with overt hypothyroidism, and between smoking and serum concentrations of total and LDL cholesterol in the women with subclinical hypothyroidism. CONCLUSIONS: Smoking increases the metabolic effects of hypothyroidism in a dose-dependent way. This may be explained by alteration of both thyroid function and hormone action.

Adult↗

Transcription factor GATA-1 regulates human HOXB2 gene expression in erythroid cells.

The human HOXB2 gene is a member of the vertebrate Hox gene family that contains genes coding for specific developmental stage DNA-binding proteins. Remarkably, within the hematopoietic compartment, genes of the HOXB complex are expressed specifically in erythromegakaryocytic cell lines and, for some of them, in hematopoietic progenitors. Here, we report the study of HOXB2 gene transcriptional regulation in hematopoietic cells, an initial step in understanding the lineage-specific expression of the whole HOXB complex in these cells. We have isolated the HOXB2 5'-flanking sequence and have characterized a promoter fragment extending 323 base pairs upstream from the transcriptional start site, which, in transfection experiments, was sufficient to direct the tissue-specific expression of HOXB2 in the erythroid cell line K562. In this fragment, we have identified a potential GATA-binding site that is essential to the promoter activity as demonstrated by point mutation experiments. Gel shift analysis revealed the formation of a specific complex in both erythroleukemic lines K562 and HEL that could be prevented by the addition of a specific antiserum raised against GATA-1 protein. These findings suggest a regulatory hierarchy in which GATA-1 is upstream of the HOXB2 gene in erythroid cells.

Amino Acid Sequence↗

[Granuloma annulare of the eyelid].

BACKGROUND: Granuloma annulare is a chronic inflammatory disease of connective tissue, manifested clinically by small, firm nodules. It is observed only rarely around the eyes. PATIENTS AND METHODS: We present four patients aged 33 to 66 years with papulomatous lesions of the eyelids. The lesions were mildly or not symptomatic. Biopsies were taken. There was no association with any systemic inflammatory disease. RESULTS: Histology was characteristic for granuloma annulare in all four cases. The clinical course was benign. CONCLUSION: When faced with papulomatous lesions of the eyelids, the ophthalmologist may consider a diagnosis of granuloma annulare in patients of any age. While granuloma annulare is generally observed in young persons, one of our patients was aged 66 years.

Adult↗