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Biomedical subjects

G Keller

Publications and source records attributed to G Keller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Case-control study on lung cancer and residential radon in western Germany.

In a 1990-1996 case-control study in western Germany, the authors investigated lung cancer risk due to exposure to residential radon. Confirmed lung cancer cases from hospitals and a random sample of community controls were interviewed by trained interviewers regarding different risk factors. For 1 year, alpha track detectors were placed in dwellings to measure radon gas concentrations. The evaluation included 1,449 cases and 2,297 controls recruited from the entire study area and a subsample of 365 cases and 595 controls from radon-prone areas of the basic study region. Rate ratios were estimated by using conditional logistic regression adjusted for smoking and for asbestos exposure. In the entire study area, no rate ratios different from 1.0 were found; in the radon-prone areas, the adjusted rate ratios for exposure in the present dwelling were 1.59 (95% confidence interval (CI): 1.08, 2.27), 1.93 (95% CI: 1.19, 3.13), and 1.93 (95% CI: 0.99, 3.77) for 50-80, 80-140, and >140 Bq/m3, respectively, compared with 0-50 Bq/m3. The excess rate ratio for an increase of 100 Bq/m3 was 0.13 (-0.12 to 0.46). An analysis based on cumulative exposure produced similar results. The results provide additional evidence that residential radon is a risk factor for lung cancer, although a risk was detected in radon-prone areas only, not in the entire study area.

Adenocarcinoma↗
PubMed2001

Gastric adenocarcinoma: pathomorphology and molecular pathology.

Two types of gastric adenocarcinoma can be distinguished histopathologically: the diffuse and the intestinal type. Molecular pathology supports this theory by showing differences in the genetic pathways of both tumor types. In addition to known pathomorphological factors of prognosis, e.g., depth of tumor infiltration, number of lymph node metastases and resection margins, a few genes have been suggested to have prognostic impact in gastric carcinoma. Clinically relevant molecules whose expression or structure is altered include the plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1), the cell cycle regulator cyclin E, epidermal growth factor (EGF), the apoptosis inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional protein beta-catenin. Gene amplification and protein overexpression of the growth factor receptors c-erbB-2 and K-sam may be prognostic factors for intestinal-type and diffuse-type gastric cancer, respectively. In addition, genetic instability is commonly seen. There has long been evidence for a genetic predisposition to gastric cancer by epidemiological studies and case reports. Very recently, germ line mutations of E-cadherin have been identified that are responsible for a dominantly inherited form of diffuse-type gastric cancer and could be used to identify individuals that are at high risk.

Adenocarcinoma↗
PubMed2001

p53 Mutations in nasal natural killer/T-cell lymphoma from Mexico: association with large cell morphology and advanced disease.

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus, and with a characteristic geographic distribution. Recently, we showed that p53 is overexpressed in a high percentage of nasal NK/T-cell lymphomas. The aim of this study was to analyze the status of the p53 gene, and correlate it with the expression of p53 protein and its downstream target, the cyclin-dependent kinase inhibitor p21, in a series of 25 cases of well-characterized nasal NK/T-cell lymphoma from Mexico. The highly conserved exons 5 to 8 of the p53 gene were amplified by polymerase chain reaction and screened for mutations by denaturing high-pressure liquid chromatography. Abnormal polymerase chain reaction products detected by denaturing high-pressure liquid chromatography and additional selected cases were sequenced. In addition, the incidence of loss of heterozygosity at the p53 locus was analyzed in 12 cases. Of the 25 patients, 17 were male and 8 female (M:F ratio, 2.1:1), with a median age of 43 years (range, 21 to 93 years). Morphologically, most of the cases were composed of a mixture of medium-sized cells and large transformed cells (21 cases), and four cases were composed exclusively of large transformed cells. Three different groups determined by p53 gene status and expression of p53 protein were identified: group 1 was p53 +/p53 mutated (five cases, all with p53 missense mutations). Morphologically, three of the five cases were composed of large cells. All five cases revealed overexpression of p53 in the majority of the tumor cells with a mean of 86%. Unexpectedly, three of these cases also showed overexpression of p21. Four of the five patients presented with clinical stage IVB and died with disease. Group 2 was p53+/p53 wild-type (10 cases). Histologically, nine cases were of the mixed type, and one of the large cell type. The percentage of p53 overexpressing cells was lower than in the previous group with a mean of 23%. p21 was positive in 7 of the 10 cases. Six patients in this group presented with clinical stages I to II and four patients with advanced disease (stage III and IV). Five patients are alive 12 to 120 months later (mean, 24 months), three with no evidence of disease. Group 3 was p53-/p53 wild-type (10 cases). All cases showed mixed cell morphology. p21 was positive in 5 of 10 cases. Four patients presented with clinical stage I to II and six patients with advanced disease. Four patients are alive with no evidence of disease 9 to 60 months later (mean, 10 months). Overall, p53 mutations were present in 24% (5 of 21) of the evaluable cases, all of them overexpressing p53 in the majority of tumor cells. Cases with p53 mutations were associated with large cell morphology (P = 0.0162) and presented more often with advanced stage disease. Loss of heterozygosity at chromosome 17p was found only in 2 of the 12 (17%) cases investigated, both cases showed p53 mutations of the remaining allele. P21 overexpression (60% of cases) is frequent in nasal NK/T-cell lymphoma and seems to be independent of p53 gene status. The overexpression of p53 and p21, independent of p53 mutations, although as yet not clear, might be the result of Epstein-Barr virus infection, and warrants further investigation.

Adult↗
PubMed2001

Isolation and characterization of structurally novel antimutagenic flavonoids from spinach (Spinacia oleracea).

Thirteen compounds, isolated from spinach (Spinacia oleracea), acted as antimutagens against the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline in Salmonella typhimurium TA 98. The antimutagens were purified by preparative and micropreparative HPLC from a methanol/water (70:30, v/v) extract of dry spinach (commercial product) after removal of lipophilic compounds such as chlorophylls and carotenoids by solid-phase extraction (SPE). Pure active compounds were identified by instrumental analysis including FT-IR, (1)H and (13)C NMR, UV-vis spectroscopy, and mass spectrometry. All of these compounds were flavonoids and related compounds that could be attributed to five groups: (A, methylenedioxyflavonol glucuronides) 5,3'-dihydroxy-4'-methoxy-6,7-methylenedioxyflavonol 3-O-beta-glucuronide (compound 1), 5,2',3'-trihydroxy-4'-methoxy-6,7-methylenedioxyflavonol 3-O-beta-glucuronide (compound 2), 5-hydroxy-3',4'-dimethoxy-6,7-methylenedioxyflavonol 3-O-beta-glucuronide (compound 3); (B, flavonol glucuronides) 5,6,3'-trihydroxy-7,4'-dimethoxyflavonol 3-O-beta-glucuronide (compound 4), 5,6-dihydroxy-7,3',4'-trimethoxyflavonol 3-O-beta-glucuronide (compound 5); (C, flavonol disaccharides) 5,6,4'-trihydroxy-7,3'-dimethoxyflavonol 3-O-disaccharide (compound 6), 5,6,3',4'-tetrahydroxy-7-methoxyflavonol 3-O-disaccharide (compounds 7 and 8); (D, flavanones) 5,8,4'-trihydroxyflavanone (compound 9), 7,8,4'-trihydroxyflavanone (compound 10); (E, flavonoid-related compounds) compounds 11, 12, and 13 with incompletely elucidated structures. The yield of compound 1 was 0.3%, related to dry weight, whereas the yields of compounds 2-13 ranged between 0.017 and 0.069%. IC(50) values (antimutagenic potencies) of the flavonol glucuronides ranged between 24.2 and 58.2 microM, whereas the flavonol disaccharides (compounds 7 and 8), the flavanones (compounds 9 and 10), and the flavonoid-related glycosidic compounds 11-13 were only weakly active. The aglycons of compounds 7 and 8, however, were potent antimutagens (IC(50) = 10.4 and 13.0 microM, respectively).

Antimutagenic Agents↗
PubMed2001

Stimulation of the growth of human tumor by low-power laser irradiation.

We studied the effect of low-power laser on the growth of human gastric adenocarcinoma transplanted to athymic mice. Irradiation shortened the latency of tumor growth in recipients from 4-6 months to 21-24 days. After 17 serial passages on athymic mice, the size of tumor node in irradiated recipients on day 33 after transplantation was 161.1 mm(3) (vs. 10.2 mm(3) in nonirradiated mice). These findings suggest that low-power laser irradiation can stimulate the growth of metastases in patients with a history of malignancy.

Adenocarcinoma↗
PubMed2001

The use of low-power laser irradiation for faster vascularization of tissue transplants.

We studied the effect of low-power laser irradiation on vascularization and take of transplanted rabbit renal and pancreatic tissue in athymic nude mice. The mean size of the transplant and the number of blood vessels in it were higher in irradiated mice compared to nonirradiated controls. Moreover, the organ-specific structure of the transplants was preserved in irradiated mice, but not in the control group. These findings suggest that low-power laser irradiation can be used for promotion of vascularization and take of tissue transplants.

Animals↗
PubMed2001

The influence of intravenous anaesthetics on the activity of enzymes released from polymorphonuclear leucocytes in vitro.

BACKGROUND AND OBJECTIVE: Polymorphonuclear leucocytes make a decisive contribution to defence against bacterial infections. In particular, the effects of anaesthetics on non-oxidative bactericidal mechanisms have previously only been superficially examined. Although the influence of anaesthetic agents on oxidative bactericidal activity has been thoroughly examined, our study concentrated on the effect on non-oxidative processes, which appears to have been a neglected field of research. METHODS: The effects of methohexital, etomidate, ketamine, fentanyl and morphine on the activity of lysozyme and beta-glucuronidase released from polymorphonuclear leucocytes have been studied in vitro. The activity of lysozyme was determined by recording the changes in the turbidity of a suspension of micrococcus lysodeicticus caused by the enzymatic action of lysozyme. beta-glucuronidase activity was photometrically measured by the enzymatic cleavage of phenolphthalein glucuronic acid. RESULTS: High concentrations of methohexital inhibited lysozyme activity; however, etomidate and morphine caused an increase of beta-glucuronidase activity in therapeutic plasma concentrations. While there was no effect of etomidate on lysozyme activity, all concentrations tested significantly stimulated beta-glucuronidase activity. This result was unexpected because intravenous anaesthetics have previously shown a tendency to suppress polymorphonuclear leucocyte functions. Whereas the inhibition of lysozyme activity by the high concentration of methohexital was no surprise, the increase of beta-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine was quite unexpected. CONCLUSIONS: At present, the underlying mechanism for the increase of beta-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine is unknown. The fact that there was no influence of these agents on lysozyme activity possibly suggests that the anaesthetic agents have different effects on azurophilic and specific granules. Since in vitro investigations have their limitations, it is too early to draw practical consequences from our study. Moreover, at present it is unclear whether an increase of beta-glucuronidase activity in vivo is an advantage or not. In any case, we think it advisable to perform further investigations on the influence of anaesthetic agents on oxygen-independent bactericidal mechanisms.

Anesthetics, Intravenous↗
PubMed2001

[Long-term results of large diameter keratoplasties in the treatment of severe chemical and thermal eye burns].

BACKGROUND: In severe chemical and thermal eye burns the limbal stem cells, which are important for the regeneration of the corneal epithelium, are lost. In our retrospective study two questions were investigated: 1) is it possible to restore the limbal region by transplantation of large diameter keratoplasties 2) has the time of transplantation an influence on the clinical outcome. PATIENTS AND METHOD: In a retrospective study the outcome of 48 eyes (43 patients) with severe chemical and thermal burns were analysed. Large diameter (11 - 12 mm) penetrating keratoplasties were performed between 1987 and 1996. Complete limbal deficiency was present in 17 eyes, while 31 eyes had developed sterile corneal ulceration. According to the time of transplantation three different groups were distinguished. Group I (early keratoplasty, n=24): transplantation within 3 months after the accident (mean: 26 days). Group II (intermediate keratoplasty, n=13): transplantation between 4 - 18 months after the burn (mean: 190 days). Group III (late keratoplasty, n=11): surgery more than 18 months after the injury (mean: 36.6 months). RESULTS: Follow-up time was 28.4 months in early keratoplasty, 26.4 months after intermediate keratoplasty, and 34.3 months in late keratoplasty. Long-term results of the keratoplasties were poor. 60.4 % of the transplants failed due to surface problems, 18.8 % due to endothelial rejection episodes. Late keratoplasties were significantly more successful than intermediate keratoplasties. 25 % of the early keratoplasties and 36.4 % of the late keratoplasties showed an intact limbal region at the end of the follow-up time, but none of intermediate keratoplasties. CONCLUSION: The prognosis for large diameter keratoplasties depends on the time of transplantation. Late and early keratoplasties had the best results. However, survival of heterologous stem cells is limited.

Adolescent↗
PubMed2001

A novel hunting accident. Discharge of a firearm by a hunting dog.

The authors report the case of a 21-year-old man who was killed while duck hunting when a shotgun accidentally discharged, shooting him in the head. The loaded weapon, which had been lying on the ground with the safety off and the muzzle pointed toward a river a few feet away, discharged when a hunting dog stepped on the trigger. Scene investigation confirmed that the victim had been standing in the river, planting decoys, with his head approximately level with the adjacent bank. Autopsy examination and ballistic testing confirmed a range of fire consistent with the witness' statements. Examination of the weapon in question documented a light trigger pull but no mechanical defects. The authors review the epidemiology and causality of hunting accidents and discuss the various safety rules that were violated in this highly unusual case. The importance of a complete death investigation, including autopsy, when dealing with a firearm death is emphasized.

Accidents↗
PubMed2001

Regulation of hemangioblast development.

The in vitro differentiation of embryonic stem (ES) cells provides a powerful approach for studying the earliest events involved in the commitment of the hematopoietic and endothelial lineages. Using this model system, we have identified a precursor with the potential to generate both primitive and definitive hematopoietic cells as well as cells with endothelial characteristics. The developmental potential of this precursor suggests that it represents the in vitro equivalent of the hemangioblast, a common stem cell for both lineages. ES cells deficient for the transcription factor scl/tal-1 are unable to generate hemangioblasts, while those deficient for Runx1 generate reduced numbers of these precursors. These findings indicate that both genes play pivotal roles at the earliest stages of hematopoietic and endothelial development. In addition, they highlight the strength of this model system in studying the function of genes in embryonic development.

Animals↗
PubMed2001

Thermal and structural behavior of anhydrous milk fat. 2. Crystalline forms obtained by slow cooling.

The crystallization behavior of milk fat has been examined on slow cooling at 0.1 degrees C/min from 50 to -15 degrees C, to determine the variations of triacylglycerol organizations as a function of temperature. The experiments have been conducted with an instrument allowing coupled X-ray diffraction (XRD) at both small and wide angles and high-sensitivity differential scanning calorimetry (DSC) recordings from the same sample by taking advantage of the high-energy flux of a synchrotron. On slow cooling, milk fat triacylglycerols sequentially crystallize in four different lamellar structures with double-chain length of 41.5, 48.3, and 39.2 A and a triple-chain length of 62.2 A stackings. Simultaneous wide-angle XRD has shown that initial nucleation occurs in a packing of beta' type at about 24 degrees C. For temperature < 13 degrees C, triacylglycerols crystallize in an hexagonal subcell of alpha type, leading to the coexistence of the beta' + alpha polymorphic forms, which is recorded until -15 degrees C. Thermal analysis allowed to correlate the formation of the different crystalline species monitored by XRDT (XRD as a function of temperature) to the exothermal events recorded simultaneously by differential scanning calorimetry. The evolution of the species formed during crystallization was also monitored on heating at 2 degrees C/min. The absence of polymorphic evolution on heating, as well as the high final melting point observed, about 40 to 41 degrees C, confirmed that cooling at 0.1 degrees C/min leads to quasi equilibrium.

Animals↗
PubMed2000

MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells.

Ligation of the high-affinity IgE receptor (FcepsilonRI) or of c-Kit stimulates cytokine production in mast cells. We show that MEK kinase 2 (MEKK2), a MAPK kinase kinase (MAP3K) that regulates the JNK and ERK5 pathways, is required for cytokine production in embryonic stem (ES) cell-derived mast cells (ESMC). Targeted disruption of the MEKK2 or MEKK1 gene was used to abolish expression of the respective kinases in ESMC. Transcription of specific cytokines in response to IgE or c-Kit ligand was markedly reduced in MEKK2(-/-) ESMC relative to wild-type ESMC. Cytokine production in MEKK1(-/-) ESMC was similar to that of wild-type ESMC, demonstrating the specificity of MEKK2 in signaling cytokine gene regulation. MEKK2(-/-) ESMC also lost receptor-mediated stimulation of JNK. In contrast, JNK activation in response to UV irradiation was normal, showing that MEKK2 is required for receptor signaling but not for cellular stress responses. MEKK2 is the first MAP3K shown to be required for mast cell tyrosine kinase receptor signaling controlling cytokine gene expression.

Animals↗
PubMed2000

Functional independence of the two cysteine-rich activation domains in the yeast Mac1 transcription factor.

Mac1 is a transcriptional activator whose activity is inhibited by copper ions. Mutagenesis studies were carried out to map residues important in the copper inhibition of Mac1 activity. Seven new missense mutations were identified that resulted in copper-independent Mac1 transcriptional activation. All seven mutations were clustered in one of two C-terminal cysteine-rich motifs, designated the C1 motif. All but one of the constitutive Mac1 mutations occurred in one of the conserved six residues in the (264)CXC[(X)(4)]CXC[(X)(2)]C[(X)(2)][H(279)]C1 motif. The lone exception was a L260S substitution. Two additional MAC1 mutations exhibiting constitutive activity were in-frame deletions encompassing portions C1. Engineered mutations in the second cysteine-rich motif did not yield a constitutively active Mac1. These results are consistent with the C1 motif being the copper-regulatory switch. Both cysteine-rich motifs exhibited transactivation activity, although the C1 activator was weak relative to the C2 activator. Limited copper metalloregulation of Mac1 was observed with only the C1 activator fused to the N-terminal DNA binding domain. Thus, the two Cys-rich motifs appear to function independently. The C1 motif appears to be a functional copper-regulatory domain.

Amino Acid Sequence↗
PubMed2000

Thermal and Structural Behavior of Milk Fat.

The thermal and structural properties of unstable varieties of triacylglycerols (TGs) crystallizing in milk fat globules of cream are examined in the range -8- +50 degrees C using a new instrument allowing simultaneously time-resolved synchrotron X-ray diffraction at both wide and small angles as a function of temperature (XRDT) and high sensitivity differential scanning calorimetry (DSC). Small angle X-ray diffraction shows that the unstable alpha form first formed by cream quenching to -8 degrees C corresponds in fact to two different lamellar phases corresponding to 2L (47 Å) and 3L (70.4 Å) arrangements of TGs. The bilayered structure is very unstable since it disappears during the course of a 20-min isothermal conditioning at -8 degrees C. On fast heating, the crystalline evolution of cream TGs demonstrates the monotropic character of their polymorphism. The structural and thermal behaviors of cream which are compared to that of its anhydrous milk fat isolated from the cream (C. Lopez et al., J. Dairy Sci., submitted) show that the crystallization occurring in emulsion droplets is similar to bulk. However, the comparison of XRD peak widths indicates that the TG crystallization is more disordered in emulsion. This disorder is attributed to the constraints due to the interface curvature in emulsion droplets. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Safety of injectable autologous human fibroblasts.

Autologous dermal fibroblasts after propagation in cell culture were used for face soft tissue augmentation. Twenty patients aged 37-61 years with facial rhytides and atrophic scars were treated with autologous fibroblasts from cell culture. Significant sustained clinical improvement was observed. Cells of early passages (4, 5, 6) were used for injection. The study showed that cultured fibroblasts were functionally active and produced large quantities of type I collagen. In vitro studies of scar formation potency of injectable fibroblasts showed that these cells possessed normal collagen gel contraction capacity. In vivo experiments showed that cultured fibroblasts exhibited no oncogenic properties and induced no tumors in nude mice.

Adult↗