Electronic structure and chemical-bonding mechanism of Cu3N, Cui3NPd, and related Cu(I) compounds.
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Journal Article↗
Biomedical subjects
U Hahn
Publications and source records attributed to U Hahn.
Thermally induced hydrogen exchange processes in small proteins as seen by FTIR spectroscopy.
Fourier-transform infrared (FTIR) spectroscopy has been used to study the thermally induced exchange characteristics of those backbone amide protons which persist H-D exchange at ambient conditions in ribonuclease A, in wild type ribonuclease T1 and some of its variants, and in the histone-like protein HBsu. The H-D exchange processes were induced by increasing the thermal energy of the protein solutions in two ways: (i) by linearly increasing the temperature, and (ii) by a temperature jump. To trace the H-D exchange in the proteins, various infrared absorption bands known to be sensitive to H-D exchange were used as specific monitors. Characteristic H-D exchange curves were obtained from which the endpoints (TH/D) of H-D exchange could be determined. The H-D exchange curves, the TH/D-values and the phase transition temperatures Tm were used to estimate the structural flexibility and stability of the given proteins. It is suggested that time-resolved FTIR spectroscopy can be used to determine global stability parameters of proteins.
Amides↗
Successful collection and transplantation of peripheral blood stem cells in cancer patients using large-volume leukaphereses.
It was the aim of our study to determine the collection efficiency and yield of CD34+ cells in 88 cancer patients (pts, 44 males/44 females) who underwent 154 large-volume leukaphereses (LV-LPs). The diagnoses were as follows: 18 patients had Non-Hodgkin's lymphoma, 9 Hodgkin's disease, 24 multiple myeloma, 6 acute leukemia, 27 breast cancer, and 4 patients had solid tumors of different types. During the course of LV-LPs, 20 liters (1) of blood were processed at a median flow-rate of 85 ml/min (CS 3000 Baxter) and 130 ml/min (COBE Spectra), respectively. Peripheral blood stem cells (PBSC) were collected following granulocyte colony-stimulating factor (G-CSF)-supported cytotoxic chemotherapy. A 31% and 21% mean decrease in the platelet and white blood count was noted at the end of the LV-LPs when compared with the pre-leukapheresis values. The aphereses were well tolerated without adverse effects. The level of circulating CD34+ cells was closely related to the number of CD34+ cells contained in the respective leukapheresis product (R = 0.89, P < 0.001). Compared with 270 patients who underwent 838 regular 10 1 LPs, the yield of CD34+ cells/kg was almost two-fold greater (4.84 +/- 0.63 x 10(6) [Mean +/- SEM] vs. 2.60 +/- 0.16 x 10(6), P < 0.001). The antigenic profile of CD34+ cells was assessed in 54 separate products collected on the occasion of 27 LV-LPs following the processing of 10 1 and 20 1, respectively. The intra-individual comparison included differentiation- as well as lineage-associated markers (CD38, Thy-1, c-kit, CD33, CD45RA). No difference in the subset composition was observed between the first and second product, arguing against a preferential release of particular CD34+ cell subsets during the procedure. As shown by molecular biological or immunocytochemical examination, the likelihood of harvesting malignant cells using large-volume aphereses was not increased in comparison with regular leukaphereses. Single harvests of > or = 2.5 x 10(6) CD34+ cells/kg could be obtained in 74% of the patients, compared with 52% in case of regular LPs. As the majority of patients were autografted with more than 2.5 x 10(6) CD34+ cells/kg following high-dose therapy, hematological recovery in general was rapid and not related to the type of apheresis product used. Considering patient comfort and savings in resource utilization, large-volume leukaphereses have become the standard procedure for PBSC collection in our center.
Adolescent↗
Ectopic growth of endometrium depends on its structural integrity and proteolytic activity in the cynomolgus monkey (Macaca fascicularis) model of endometriosis.
OBJECTIVE: To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis. DESIGN: Prospective, comparative study. SETTING: Animal research unit. SUBJECTS: Thirty regularly cycling cynomolgus monkeys in three groups of 10 each. INTERVENTIONS: Endometrium was minced and spilled into the cul-de-sac in group 1. In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor. MAIN OUTCOME MEASURES: Staging laparotomies after 3 weeks and 3 months. RESULTS: In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3 weeks and in eight, three, and two monkeys, respectively, at 3 months. CONCLUSIONS: An intact structure leads to ectopic implantation of endometrial fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.
Animals↗
Delineation of segmental liver anatomy. Comparison of ultrasonography, spiral CT and MR imaging for preoperative localization of focal liver lesions to specific hepatic segments.
PURPOSE: The purpose of this study was to determine the ability of noninvasive imaging methods to localize focal liver lesions to specific hepatic segments. MATERIAL AND METHODS: In a prospective study we evaluated 24 patients with hepatic masses with ultrasonography (US), spiral CT and MR imaging. RESULTS: The primary segmental location of the lesions was correct with US in 15 of 24 patients (63%), with CT in 21 of 24 patients (88%) and with MR imaging in 17 of 22 patients (77%). The full extent of the lesions was correctly described with US in 9 of 24 patients (38%), with CT in 16 of 24 patients (67%) and with MR in 12 of 22 patients (55%). CONCLUSION: Among the noninvasive imaging methods, CT provides the best information for determining the segmental location and planning the surgical approach to hepatic resections.
Contrast Media↗
[Management of abdominal stab wounds].
In general, laparotomy is accepted as treatment of choice for abdominal shot wounds. However, the management of abdominal stab wounds is controversial. In order to study the concept of laparotomy for penetrating abdominal trauma our patient collective was analyzed retrospectively. From 1st January 1985 to 31st December 1993 we performed laparotomy in 30 cases of abdominal stab wounds. 24 patients were victims of violence. In 6 patients the cause of injury was a suicidal attempt. Laparotomy was negative in 27% of cases. In most cases explorative laparotomy showed injuries of the vessels (n = 12) and the intestines (n = 9). The mortality rate was 6.7%. None of the fatal cases was caused by negative laparotomy. During a mean follow-up time of 54 months none of the patients showed disorders of late onset after negative laparotomy. Because of the limited diagnostic possibilities to rule out intestine injury and minimal morbidity of negative laparotomies we continue to favour laparotomy in the management of penetrating abdominal trauma.
Abdominal Injuries↗
[Ovarian tumors and pregnancy].
Ovarian tumors during pregnancy are a rare event. In most cases the tumors are detected accidentially during routine examination, ultrasound or a caesarean section at term. The incidence of malignant ovarian tumors is about 1:10,000 to 1:40,000 pregnancies. Histologic subtypes and prognosis do not differ from tumors not associated with pregnancy, it seems however, that there are more lesions of borderline malignancy and of low grade. Therapy depends mostly on the age of gestation and tumor stage. Conservative surgery is recommended only in stage IA disease. Radical surgery and if necessary adjuvant therapy is recommended during the first trimester. In the third trimester a caesarean section can be followed by radical surgery, provided that there is a close cooperation between gynecologists and pediatricians. In the second trimester this regimen is possible only as an exception which includes a critical maternal risk-benefit assessment.
Cesarean Section↗
[Morphologic endometrium changes with tamoxifen].
Women receiving tamoxifen as adjuvant therapy for breast cancer usually develop atrophy of the endometrium. Cystic polyps as well as endocervical and clear-cell metaplasias also frequently arise in the these atrophic endometria. The invasive endometrial carcinomas we have observed in these women have all been until now either mucinous, clear-cell or serous-papillary carcinomas, that is, different from the endometrioid type of adenocarcinomas that arise under estrogenic stimulation. Our histological studies support the assumption that tamoxifen has an antiestrogenic, gestagen-like action on the endometrium; they contradict the premise that tamoxifen therapy exerts an estrogen effect.
Antineoplastic Agents, Hormonal↗
Automatic knowledge acquisition from medical texts.
An approach to knowledge-based understanding of realistic texts from the medical domain (viz. findings of gastro-intestinal diseases) is presented. We survey major methodological features of an object-oriented, fully lexicalized, dependency-based grammar model which is tightly linked to domain knowledge representations based on description logics. The parser adheres to the principles of robustness, incrementality and concurrency. The substrate of automatic knowledge acquisition are text knowledge bases generated by the parser from medical narratives, which represent major portions of the content of these documents.
Artificial Intelligence↗
SaRD, a new protein isolated from the extremophile archaeon Sulfolobus acidocaldarius, is a thermostable ribonuclease with DNA-binding properties.
We have isolated the thermostable 9 kDa SaRD-protein from Sulfolobus acidocaldarius which exhibit RNase activity as well as DNA-binding properties (SaRD). The amino acid composition and the sequence of the 16 N-terminal amino acids show similarities to different RNases as well as to DNA-binding proteins from thermophilic archea. The RNase activity was demonstrated by 5S rRNA degradation, thin layer chromatography and a zymogram. The temperature optimum for the RNase activity is 65 degrees C. The pH optimum ranges from 6.5-7.0. DNA-binding properties were shown by gel-shift assays on agarose gels. In a similar way SaRD mediated protection of DNA against DNase I digestion and Sau3A I restriction could be demonstrated. The melting point (Tm) of genomic DNA was raised from 68 degrees C to 90 degrees C by addition of the SaRD-protein. CD spectroscopy indicated that SaRD is very stable near neutral pH and can neither be unfolded by temperatures up to 85% C nor by addition of 8 M urea.
Amino Acids↗
Destabilization of a protein helix by electrostatic interactions.
Electrostatic interactions between charged residues and the helix dipole in a protein were investigated by protein engineering methods. In ribonuclease T1, two surface-exposed acidic residues (Glu28 and Asp29) are located near the carboxyl terminus of the alpha-helix between residues 13 and 29. They were replaced, individually and in concert, by the uncharged amides Gln28 and Asn29, and the stabilities of the wild-type protein and its variants were determined as a function of pH. The effects of the two mutations are additive. Either one leads to a marginal destabilization by 0.7 kJ/mol at pH 2 but to a strong stabilization by about 3.2 kJ/mol at pH 7. This suggests that the deprotonations of Glu28 and Asp29 reduce the free energy of stabilization of folded ribonuclease T1 by about 4 kJ/mol each. This destabilization is probably caused by unfavorable electrostatic interactions of Glu28 and Asp29 with the negative end of the helix dipole. The activation energies for the unfolding of the different variants of ribonuclease T1 change in parallel with the differences in the thermodynamic stability when the pH is varied. This indicates that the unfavorable electrostatic interactions of Glu28 and Asp29 are lost very early in unfolding, and are not present in the activated state of unfolding.
Asparagine↗
Large-bore central venous catheters for the collection of peripheral blood stem cells.
In order to establish a peripheral blood stem cell graft, repeated apheresis are necessary in the majority of patients. Each apheresis requires withdrawal and reinfusion of blood with high flow rates. To guarantee these flow rates, large-bore catheters are needed for central venous access. Subcutaneously tunneled silicone catheters (Hickman) caused venous thrombosis in 10-40% of the patients. We therefore used polyurethane large-bore catheters only for the time of peripheral blood stem cells (PBSC) collection. Via a Seldinger guidewire following delineation of the right (160 patients) or left (23 patients) internal jugular vein by ultrasound, 183 apheresis catheters have been inserted when the white blood cell count was > 1.0 x 10(9)/L and a measurable population of CD34+ cells was detected by fluorescence-activated cell sorter analysis. The median flow rate was 70 ml/min (range 50-80 ml/min). We observed the following complications: puncture of the carotid artery in 2%, pneumothorax in 0.5%, local infection in 3%, and catheter-related septicemia in only 2% of the patients. At the time of the removal of the catheters, we detected thrombosis of the internal jugular vein in 5% of the patients by ultrasound. The collection of PBSC with short-term, large-bore catheters is effective and is associated with a low incidence of infection and thrombosis.
Acinetobacter Infections↗
Prevention of catheter-related infections by silver coated central venous catheters in oncological patients.
Catheter-related infection (CRI) is a serious complication of central venous catheterization. We have investigated the efficacy of a silver-coated polyurethane catheter (Pellethane, Fresenius AG, Germany) in preventing CRI in oncological patients receiving chemotherapy in a phase II study. From November 1992 through April 1994, 266 patients were assigned to receive single lumen catheters, either standard uncoated catheters (UC, n = 113) or silver-coated ones (SC, n = 120). Catheters were inserted into the internal jugular vein after institutional approval and informed consent. Duration of catheterization (UC vs. SC = 13.3 vs. 12.7 days) and leukopenia (< 1.0 x 10(9) WBC/l; 4.3 vs. 3.6 days) were similar in both groups demonstrating a comparable risk for infections. Skin reactions at the catheter entry site were recorded daily. CRI and colonization rates were studied by semiquantitatively culturing intradermal and intravascular segments. CRI were confirmed by blood cultures obtained via catheter and from peripheral veins in cases of suspected sepsis or at the end of catheterization. No adverse effects from the silver-coated catheter could be observed. The bacteriological results showed that SC were colonized (> 15 CFU) in 45.1% and UC in 44.2%. CRI developed in 21.2% of the UC patients but only in 10.2% of the SC patients (p = 0.011). We conclude that this new silver-coated central venous catheter is biocompatible and effective in reducing the incidence of catheter-related infections in oncological patients.
Adolescent↗
Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antiestrogens (tamoxifen) and gestagens.
In recent years, tamoxifen therapy for breast carcinoma has been associated with endometrial carcinoma with increasing frequency. We describe 10 cases of this association as well as 12 cases of endometrial carcinoma after therapy with synthetic gestagens. All but one of the 22 carcinomas we describe here were of the mucinous or clear cell type, and arose in atrophic endometria containing foci of mucinous (endocervical) and clear cell metaplasia. In the endometrium, the antiestrogenic action of tamoxifen closely resembles the antiproliferative action of synthetic gestagens on the endometrium. In the endocervix, tamoxifen as well as synthetic gestagens, stimulate the endocervical mucosa to proliferate. In the endometrium, both tend to produce mucinous (endocervical) and clear cell metaplasia. A weak estrogenic action of tamoxifen may be expected to augment its own antiestrogenic gestagen-like action. Consequently, the antiestrogenic effect of tamoxifen is most likely responsible for the development of endocervical metaplasia and possibly corresponding endocervical and clear cell types of carcinomas within an atrophic endometrium. We believe that gestagen therapy administered to patients with endometrioid type carcinoma is contraindicated in patients with mucinous adenocarcinoma of the endometrium and that this is another reason to distinguish between these two types of carcinoma.
Adenocarcinoma, Clear Cell↗
Identification of a novel HLA-A33 subtype (A*3303) and correction of the A*3301 sequence.
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Alleles↗
A novel HLA-A24 allele (A*2405) identified by single-strand conformation polymorphism analysis and confirmed by solid-phase sequencing and isoelectric focusing.
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Alleles↗
Complete subtyping of the HLA-A locus by sequence-specific amplification followed by direct sequencing or single-strand conformation polymorphism analysis.
A variety of reasons related to the HLA class I system has complicated the application of molecular approaches to HLA class I typing. Here we present a PCR-based HLA-A typing strategy considering the sequence variations of the two most polymorphic exons which allows complete subtyping of the HLA-A locus. The method is based on a sequence-specific amplification identifying the serologically defined HLA-A specificities. The PCR products generated by these group-specific primers bear the sequence information necessary for a postamplification specificity step. The primer pairs are located within one exon, either exon 2 or exon 3, which avoids amplification of polymorphic intron sequences allowing subsequent single-strand conformation polymorphism analysis and facilitating direct sequencing. Using this method we investigated 48 cell lines and 153 clinical samples. 23 PCR reactions are performed per individual for the assignment of the serological specificities A1-A80. The reproducibility was 100% in all cell lines and 85 clinical samples typed on two separate occasions. With the exception of 13 out of 231 possible serological combinations all homozygous and heterozygous combinations of A1-A80 can be distinguished by specific amplification patterns. Comparing the PCR based typing results with those of serology in 12% a discrepancy was found. Solid-phase sequencing or SSCP analysis of the group-specific PCR fragments allowed complete subtyping of the HLA-A locus. This strategy can identify all 48 HLA-A alleles based on the sequence variations of the 2nd and 3rd exon. 1128 homozygous and heterozygous allele combinations are possible for the HLA-A locus. Only 4 out of these 1128 allele combinations remained unresolved.
Alleles↗
A novel HLA-A30 allele (A*3004) identified by single-strand conformation polymorphism analysis and confirmed by solid-phase sequencing.
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Alleles↗