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Biomedical subjects

A Beck

Publications and source records attributed to A Beck.

At least 163 records · Page 9Linked to original sources

Topographic patterns of odorant receptor expression in mammals: a comparative study.

In a comparative study, molecular probes for various odorant receptor subtypes were employed in in situ hybridization experiments on tissue sections through the nose from different mammalian species. OR37 reactive neurons were found exclusively in the rodent species, where they were clustered in very similar position within the nasal cavities; an OR37-related receptor subtype was not detectable in the rabbit. All other subtypes tested, hybridized across species borders to neurons that were distributed within the distinct zones of the olfactory epithelium. Most receptor types were found in the same zone in all species; however, a few subtypes which are expressed in the medial zone in rat were found in the dorsal zone in guinea pig.

Animals↗

The relation between depth of trophoblastic invasion and beta-HCG levels in tubal pregnancies.

beta-HCG (human chorionic gonadotropin) values of over 2500 I.U./l are associated with higher failure rates for therapy with prostaglandin F2 alpha in tubal pregnancies. The purpose of our study was to ascertain if the 2500 I.U./l limit correlates with histopathology. We therefore compared the pre-operative beta-HCG-values and intraluminal and extraluminal trophoblast growth in tubal pregnancy. Purely intraluminal trophoblast was significantly more frequent in patients of group I (beta-HCG < 2500 I.U./l), while group II patients (beta-HCG > 2500 I.U./l) almost exclusively had extraluminal growth (P = 0.0045). Since the efficacy of prostaglandin F2 alpha therapy depends on intact tubal musculature the correlation of the beta-HCG threshold level with histopathologic findings may explain the high failure rate in patients with beta-HCG values above 2500 I.U./l.

Chorionic Gonadotropin↗

Carriage of Streptococcus pyogenes among infants and toddlers attending day-care facilities in closed communities in southern Israel.

Infants and toddlers attending ten day-care facilities in closed communities in southern Israel were tested monthly for pharyngeal carriage of Streptococcus pyogenes and associated respiratory morbidity. Overall, the prevalence of Streptococcus pyogenes was 2.7% in infants and 8.4% in toddlers, reaching 8.5% and 17.8% in the two groups, respectively by midwinter. In 4 of 61 (6.6%) infants and 15 of 67 (22.4%) toddlers, the organism was recovered in more than one month (range 2 to 5 months). Streptococcus pyogenes in the pharynx was only associated with rhinitis during the spring and summer but not with other respiratory symptoms. During the study period, a mean of 0.9 strains were isolated in day-care facilities attended by infants, while a mean of 2.1 strains were found in toddlers. Young children attending day-care facilities show early acquisition of Streptococcus pyogenes in the pharynx.

Carrier State↗

Alpha-methyl-proline restores normal levels of bone collagen Type I synthesis in ovariectomized rats.

Collagen type I is the major protein of bone matrix and significantly reduced in osteoporosis. We tested the effect of alpha - methyl - proline on collagen synthesis in the model of the ovariectomized rat. Collagen synthesis was studied at the transcriptional level using Northern and dot blotting and at the protein level using hydroxyproline determination and a specific dye binding collagen assay. Alpha - methyl- proline treatment significantly increased collagen synthesis as compared to untreated ovariectomized and estradiol treated ovariectomized rats and restored collagen synthesis to levels of sham operated rats. Proline analogues were described to stimulate procollagen synthesis at the transcriptional level, however, if incorporated, lead to negative collagen production due to rapid intracellular degradation of the deficient collagen. Our synthesized analogue is not being incorporated, thus not interfering with collagen conformation and can therefore induce collagen production.

Animals↗

Effects of contralateral white noise stimulation on transitory evoked otoacoustic emissions in patients with acoustic neuroma.

Transitory evoked otoacoustic emissions are normal phenomena observed in most persons with hearing levels greater than 35 dB. Further, masking of the contralateral ear produces amplitude reductions in the transitory evoked otoacoustic emissions. We have undertaken a study of transitory evoked otoacoustic emissions in 20 patients with acoustic neuroma. All patients were assessed for transitory evoked otoacoustic emissions bilaterally, with and without contralateral masking with white band noise at 40, 50, and 60 dB. We found that transitory evoked otoacoustic emissions were present in 30% of ears with tumor and that the presence of transitory evoked otoacoustic emissions is associated with improved preoperative hearing levels, but that tumor size is not associated with the presence or absence of transitory evoked otoacoustic emissions. The amplitude of transitory evoked otoacoustic emissions from ears with tumor, when present, is decreased when compared with normal ears of normal patients. Further, with contralateral masking little of the amplitude reduction observed in normal patients is observed in the ears with acoustic neuroma. However, with masking of the contralateral ear, the ear without tumor demonstrated significantly greater amplitude reductions than normal ears from normal patients (p = 0.0006). Pertinent anatomy and possible explanations for these findings are discussed.

Acoustic Stimulation↗

[Histopathologic findings of the trophoblast and tubal wall after medicamentous therapy of tubal pregnancies].

The purpose of the study was to evaluate the effects of drug therapy on the throphoblast and on the tubal wall when protaglandin F2 alpha (PGF2 alpha) was administered in cases of tubal pregnancies. 42 patients were divided into two groups: women of group I (n = 30) were secondarily treated by surgery because of raising serum HCG levels. Group II (n = 12) consisted of patients who were operated on because of acute symptoms (abdominal pains, intraabdominal haemorrhage), despite already failing HCG values. In group I in 66% (n = 20) of the histological specimens an intact (vital) trophoblast was found. Five cases (17%) showed partly necrotic gestational tissue, whereas in another five cases (17%) the whole trophoblast was necrotic. In patients of group II all ectopic pregnancies showed histological signs of necrosis. In the histopathology of the Fallopian tubes no signs of trophic regression could be found. However, ten out of 22 cases showed ruptured tubal pregnancies. In this analysis we could show that the instillation of PGF2a electively destroys the ectopic trophoblast and does not exercise any necrotic action on the tubal wall.

Abortifacient Agents, Nonsteroidal↗

Impact of trophoblast penetration through the basal membrane on the efficacy of drug therapy in tubal pregnancies.

Concentrations of beta-human chorionic gonadotrophin (HCG) of 2500 IU/l are generally considered to be maximal for successful drug therapy of tubal pregnancies [instillation of prostaglandin-F2 alpha (PGF2 alpha) or hyperosmolar glucose]. The purpose of our study was to ascertain if there was an association between the significantly higher failure rates above this threshold value and the histologically determined anatomopathological substratum. We therefore evaluated the impact of trophoblast penetration through the basal membrane of the Fallopian tube on the efficacy of drug therapy. Pre-operative serum beta-HCG concentrations were compared with the histologically determined trophoblast penetration, distinguishing between ectopic pregnancies with intra-luminal growths up to the myosalpinx, and those with extra-luminal growths going beyond the basal membrane and penetrating the myosalpinx. Basic data were obtained from a group of patients who received primary surgical treatment but it had never been the intention for them to receive drug therapy (independently of their initial beta-HCG values; group I, n = 43). These reference data were compared with the findings in preparations from another group of patients obtained during secondary surgical intervention, performed to achieve final cure of tubal pregnancy after failure of primary PGF2 alpha instillation (group II, n = 30). Group I patients showed a significantly higher rate of intra-luminal trophoblast growths (P = 0.0001) at beta-HCG values < 2500 IU/l; above this threshold value, extra-lumina spread was found significantly more often (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Proliferative activity in ectopic trophoblastic tissue.

Clinical observations have shown that tubal pregnancies develop individually different biological activities such as different growth rates, levels of beta human chorionic gonadotrophin (beta-HCG), or rates of tubal wall destruction. In the present study, we evaluated the proliferative activity of ectopic cytotrophoblastic tissue using immunocytochemistry with antibodies to Ki-67 (clone MIB-1). The rates of proliferation obtained were related to the maternal serum beta-HCG values. Reference data were obtained from placentas of intact intrauterine pregnancies (group I, n = 14). The proliferative activity of this tissue was compared to that of cytotrophoblastic tissue of tubal pregnancies (group II, n = 27). Ki-67-immunostained as well as non-stained cytotrophoblastic nuclei of the villi and the trophoblastic columns were counted separately, and results were expressed as percentage of positive cells. Serum beta-HCG values were determined twice, 48 h and immediately before operation. The cytotrophoblastic cells of intact intrauterine pregnancies (group I) showed uniform and high proliferative activities (80% on average in villi, 84% on average in columns). The average Ki-67 proliferation rate was significantly lower (P < 0.001) in trophoblastic tissue of tubal pregnancies (group II; 42% on average in villi, 61% on average in columns). Within the group of tubal pregnancies, higher intragroup differences were observed. The number of Ki-67-labelled cells was independent of the absolute preoperative serum beta-HCG values in both groups, yet they were clearly related to the relative increase of beta-HCG in maternal serum. At higher proliferation rates, there was a significant, growing increase of beta-HCG values (P < 0.01). We have found immunohistochemical evidence to support the previous clinical speculations that tubal pregnancies develop more heterogeneously and more slowly than intact intrauterine pregnancies. The development of the beta-HCG concentrations may be taken as an indirect parameter, reflecting proliferative activity of the trophoblast.

Cell Division↗

[VLA and alpha6, beta4 integrins. Expression in normal and neoplastic human tissues].

Among the cellular adhesion molecules, the integrin family, more particularly the VLA (Very late antigen) integrins, is currently the subject of numerous investigations in pathology. These integrins are involved in cell-cell contact or cell-matrix adhesions. During neoplastic diseases, cellular expression of integrins changes and a study of the modifications could allow a new etiopathogenic approach carcinogenesis and metastatic phenomena. New prognostic factors may be defined in tumor pathology. We describe the general structure of integrins and the mechanisms of their binding with matricial ligands and with cytoskeleton. The expression of VLA integrins and the alpha6beta4 heterodimer on normal and neoplastic human tissues is then described. Finally, we describe the involvement of these proteins in tumor progression and tissue invasion.

Antigens, CD↗

Lymphogenous metastasis in the primary carcinoma of the fallopian tube.

The bad prognosis of primary Fallopian tube carcinoma (FTC) is mostly ascribed to early lymphogenous metastasis. Yet, there is a lack of information on the tumor size at which lymph node metastasis must be expected to occur. Our study was therefore designed to correlate the anatomopathologic substratum and the histologic results with the lymph node status. Data were obtained from 21 women who received primary surgery, during which additional total pelvic and para-aortic lymphadenectomy was performed as well. The "surgical" staging was compared to the final clinical staging after histologic inspection of the lymph nodes according to the FIGO classification. Lymph node metastases never occurred as long as the tumor was confined to the tube (stage I). Lymphogenous dissemination set in only after further, local expansion of the tumor, involving the ovaries, the peritoneum, or the uterus (surgical stage II); 3 of the 7 patients of surgical stage II had to be reclassified to stage III because of manifest lymph node metastases. After the onset of intra-abdominal or general metastasis (stage IV), lymph node metastases occurred significantly more often (P = 0.048). Due to the specific lymphatic drainage, lymphogenous metastasis must be expected to spread as far as to the para-aortic region even in the early stages. Highly differentiated tumors (G I) do not disseminate into the lymphatic system, not even in advanced stages, whereas anaplastic tumors (G II and III) metastasize relatively early. As soon as metastasis has occurred, prognosis of life diminishes markedly, but not significantly (49 versus 24 months, P = 0.19). Correct FTC-staging is obtained only on the basis of pelvic and para-aortic lymphadenectomy.

Adolescent↗

Rostro-caudal patterning of receptor-expressing olfactory neurones in the rat nasal cavity.

The rostro-caudal extent of odorant receptor expression zones in the rat olfactory epithelium was analysed by means of in situ hybridization. Three broad non-overlapping zones were identified that extended along almost the entire anterior-posterior axis; each zone was composed of several separate bands running anterior to posterior throughout the olfactory epithelium. Super-imposed onto these broad zones was the expression area of a particular receptor subtype (OR37); it was restricted to a small region of the epithelial sheet with a high density of reactive neurones in the centre and declining numbers towards the periphery of the region. A quantitative evaluation of the reactive cells revealed that, despite their different distribution patterns, all receptor subtypes were expressed in an equal number of neurones.

Animals↗

Olfactory neurones expressing distinct odorant receptor subtypes are spatially segregated in the nasal neuroepithelium.

In situ hybridization techniques have been employed to explore the olfactory epithelium of the rat for the distribution of odorant receptor gene transcripts. We demonstrate that olfactory neurone subpopulations expressing distinct receptor subtypes are spatially segregated within the olfactory epithelium. A compartmentalization of the neuroepithelium into distinct expression zone is apparent, cells expressing a specific receptor are randomly distributed within a given zone. Structurally related receptor subtypes share a common distribution pattern.

Animals↗

Evaluation of adjuvant therapy after surgery for primary carcinoma of the fallopian tube.

OBJECTIVE: To evaluate the impact of postoperative therapy (chemotherapy vs. irradiation) on overall survival. DESIGN: A nationwide retrospective analysis. SETTING: Hanusch-Krankenhaus, Department of Gynaecology, SUBJECTS: 115 patients with histologically proved primary carcinoma of the Fallopian tube: 49 received six treatment cycles of a cis-platinum regimen (group I), 24 patients were treated by full irradiation using 50 Gray minimum (group II). The two groups had a similar distribution of stage I and II; in the more advanced stages chemotherapy was the predominant method of treatment. RESULTS: The five-year survival rate was 53% for women receiving irradiation as against 27% for those given cis-platinum. If the analysis was restricted to those patients with comparable stage I and stage II lesions, the p-value (0.07) was of borderline significance. There was no advantage in adding abdominal to pelvic irradiation (P = 0.62). CONCLUSIONS: Stage I and stage II carcinoma is probably better treated postoperatively by radiotherapy than chemotherapy. Chemotherapy may have more therapeutic potential in patients with more advanced lesions.

Adult↗

Primary fallopian tube carcinoma--a retrospective survey of 51 cases. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

OBJECTIVE: To evaluate retrospectively the importance of invasion beyond the basement membrane on overall survival in Fallopian tube carcinoma and its influence on the necessity of postoperative adjuvant therapy (stage 0 vs. stage I). DESIGN: In a nationwide analysis the data of 51 patients were evaluated. The participating departments provided the study center with histologic specimens. A re-staging was done according to the FIGO-classification for Fallopian tube carcinomas. Stage 0 patients received no further postoperative therapy, in stage I patients were divided in 2 groups to evaluate the impact of postoperative adjuvant therapy (chemotherapy vs. irradiation). RESULTS: Patients of stage 0 had a significantly better prognosis than patients of stage I (p = 0.035). Stage I patients treated by irradiation showed a significantly better prognosis than patients treated by chemotherapy (p = 0.017). CONCLUSION: Tumour penetration through the basement membrane causes prognosis to deteriorate significantly (5-year survival rate about 50% in stage I). Postoperative therapy is thus indicated with stage I disease. Irradiation seems to give better results than chemotherapy.

Adenocarcinoma↗

A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil.

Despite being one of the oldest anti-cancer drugs, fluorouracil (FU) is still being increasingly used in cancer chemotherapy. The source of variability for FU sensitivity in patients may be complex, although an overproduction of thymidylate synthase (TS) was the only mechanism of resistance identified in tumours from FU-resistant patients. Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme of FU catabolism. Thus, DPD activity may be a potential factor for controlling FU responsiveness. A panel of 19 human tumour cell lines, including digestive tract, breast and head and neck cancer cells, were investigated. Both TS and DPD activities were measured in parallel to FU responsiveness. None of the cell lines had been previously exposed to FU, and thus expressed a spontaneous sensitivity to FU. Sensitivity between cell lines showed marked differences, with IC50 values ranging from 45 ng/ml (colon cell line) to 5063 ng/ml (head and neck cell line). TS activity was measurable in all cell lines and varied within a 46-fold range. DPD activity was detected in all but four cell lines, showing a 100-fold range of variation. Cell lines most sensitive to FU exhibited the lowest DPD and TS activities and vice versa. Simple linear regression analysis showed that both TS (r2 = 0.22, P = 0.042) and DPD (r2 = 0.27, P = 0.022) activities were significantly correlated to FU effectiveness (log 10 IC50): the greater the enzyme activities, the higher the FU IC50. TS and DPD were demonstrated to be independent variables. A multiple regression analysis showed that the combination of TS and DPD activities explained 36% of the variability in FU IC50 (r2 = 0.36, P = 0.01). Two groups of cell lines could be identified, one group with both low TS and low DPD activities (G1), and the other with either high TS and/or high DPD activities (G2). Mean FU IC50 values were 193 and 930 ng/ml in G1 and G2, respectively, and this difference in FU sensitivity was highly significant (P = 0.009). The present study shows, for the first time, that DPD activity in tumour cells is an independent factor significantly related to FU sensitivity. These results should encourage DPD and TS coupled measurements in tumours of patients before FU treatment in order to establish their prognostic relevance. DPD and TS measurements could also be used during the treatment course to determine the implication of these enzymes in the development of tumour resistance to FU.

Breast Neoplasms↗

Wide range for optimal concentration of folinic acid in fluorouracil modulation--experimental data on human tumour cell lines.

The clinical use of the fluorouracil (FU)-folinic acid (FA) combination is hampered by the still open choice of the optimal schedule, with marked controversy as concerns the optimal FA dose. This in vitro study on FU-FA combinations in 17 human cancer cell lines, representative of tumour types responding to FU-FA treatment, reassesses the notion of the optimal FA concentration. Cells were exposed for 5 days to various FU-FA concentrations (0.07-77 microM, 14 concentrations, for FU; and 0.0025-100 microM for FA). The growth inhibition was assessed by the MTT test. The investigated cell lines exhibited FU IC50 ranging from 0.4 to 38.9 microM (median 3.7 microM). In six out of 17 cell lines investigated, the addition of FA did not result in a substantial enhancement of FU cytotoxicity (group 1). For the remaining 11 cell lines responding to FA supplementation (group 2), the maximal enhancement factor ranged from 3 to 8, meaning that in the presence of optimal FA concentration, the efficient FU concentration (IC50) was reduced by between 3 and 8 as compared to the efficient FU concentration without FA supplementation. For cell lines responding to FA supplementation, the optimal FA concentrations ranged from 10(-7) to 4 x 10(-4) M (4000-fold range) with a median value at 9.6 x 10(-7) M. Distribution of cell doubling time was not significantly different between group 1 and group 2. In contrast, the FU IC50 were significantly different (P = 0.02) between group 1 (median 7.4 microM) and group 2 (median 2.2 microM), thus indicating that cell lines with the greatest FU cytotoxicity enhancement by FA were those intrinsically sensitive to FU and vice versa.

Breast Neoplasms↗