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Biomedical subjects

A Budinsky

Publications and source records attributed to A Budinsky.

11 recordsLinked to original sources

Daily prickly pear consumption improves platelet function.

Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.

Adenosine Diphosphate↗

Endovascular brachytherapy in peripheral arteries.

Increasing knowledge about the pathophysiology of the process leading to restenosis has given the rationale to investigate the potential role of radiation in the prevention of restenosis. Compared to the rapidly increasing experience in the coronary circulation, there is until now only a limited number of studies concerning the use of brachytherapy (BT) in the peripheral circulation. The-Vienna 2-Trial was the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty. The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA + BT-group and 35.3% in the PTA-group (p < 0.005), and the significant improvement in patency was also maintained after two years. The results of two ongoing randomized, double-blinded multicenter trials (PARIS; Vienna 3) have to be awaited before definitive recommendations can be given. The rather high incidence of late thrombotic occlusion after long-segment femoropopliteal stenting and endovascular BT requires optimization of the antithrombotic regimen.

Angioplasty, Balloon↗

Anti-Her-2/neu antibody induces apoptosis in Her-2/neu overexpressing breast cancer cells independently from p53 status.

Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53.

Antibodies, Monoclonal↗

Regular ingestion of opuntia robusta lowers oxidation injury.

The influence of opuntia robusta (prickly pear), a traditionally used dietary nutrient against diabetes mellitus among the American Indian population, was examined in 15 young patients suffering from familial heterozygous isolated hypercholesterolemia. Oxidation injury was determined via 8-epi-PGF(2 alpha)in plasma, serum and urine. Daily consumption of 250 g broiled edible pulp of prickly pear had no influence on body weight and body fat composition. Total cholesterol was lowered (P<0.01) as was LDL-cholesterol (P<0.04). No significant changes were observed either in triglycerides or in HDL. Prickly pear induced a significant decrease in plasma (27.9+/-3.3-->25.6+/-3.2;P<0.03), serum (302.0+/-11.4-->283.2+/-14.5;P<0.0003) and urinary (355.9+/-18.4-->323.9+/-16;P<0.00002) 8-epi-PGF(2alpha)values. The findings on a decrease of 8-epi-PGF(2alpha)were more pronounced in females than in males, the highest significance being found in urine, while, in contrast, the effects on total- and LDL-cholesterol were more pronounced in males. A prerunning 4 weeks period of dietary counseling had no significant effect on either of the parameters examined. These findings indicate that the regular ingestion of opuntia robusta is able to significantly reduce in-vivo oxidation injury in a group of patients suffering from familial hypercholesterolemia. This traditional food of the American Indians thus may have a significant cardiovascular benefit.

Adult↗

Karyotypic findings in two cases of male breast cancer.

Male breast cancer is uncommon; so far, only 10 cases with chromosome banding analysis have been published. We report the cytogenetic findings of two invasive breast cancers in two Caucasian men lacking a history of familial breast cancer and more than 70 years of age. Both had ductal carcinomas with lymphangiosis carcinomatosa and positive lymph nodes at diagnosis. Strong expression of estrogen receptor, weak expression of progesterone receptor, and lack of expression of androgen receptor by both tumors were demonstrated by immunohistochemistry, as well as lack of expression of p53 and C-ERB-B-2. The karyotypes were 45 approximately 46,XY,-Y[4],-7[2],+8[2],t(8;12)(q21;q24)[3], del(9)(q22)[3],del(11)(p11p14)[5],del(18)(q21)[7], t(19;20)(p10;q10)[8] [cp13] and 61 approximately 69,XXXY,-Y[3], del(2)(p21)[4],del(3)(p22q26)[3],-4,-4[5],+5,+5[5], dic(5;11)(p14;q23)[3],del(6)(q23)[4],del(8)(p21)[3],-9[4],-11[4],+ i(12)(p10)[4],-16[3],del(17)([13)[5],del(18)(q21)[4],+19[5], +20[4][cp7], respectively. Although the available data on male breast cancer are still very limited, our findings confirm that gain of an X chromosome, loss of the Y chromosome, gain of chromosome 5, and loss of material from chromosomes 17 and 18 are nonrandom aberrations in male breast cancer. Trisomy 8, characteristic of ductal carcinomas, was found in one case.

Aged↗

Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-alpha and retinoids.

Uncontrolled proliferation and a defect of apoptosis constitute crucial elements in the development and progression of tumours. Among many other biological response modifiers known to influence these mechanisms, the efficacy of retinoids and interferons in the treatment of various malignant entities is currently matter of discussion. In the present study, we have investigated the effects of 9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), all-trans-retinoic acid (tRA) and interferon-alpha on proliferation and apoptosis of human soft tissue sarcoma (STS) cell lines HTB-82 (rhabdomyosarcoma), HTB-91 (fibrosarcoma), HTB-92 (liposarcoma), HTB-93 (synovial sarcoma) and HTB-94 (chondrosarcoma) in relation to p53 genotype as well as p53 expression. HTB-91, HTB-92 and HTB-94 STS cells exhibited mutant p53, whereas wild-type p53 was found in HTB-93 STS cells, and a normal p53 status in HTB-82 STS cells, carrying a silent point mutation only. Interferon-alpha, irrespective of p53 status, inhibited the proliferation of all five cell lines dose- and time-dependently. Similarly, 9cRA, 13cRA and tRA decreased the proliferation of HTB-82 and HTB-93 STS cells, whereas the proliferation of p53-mutated HTB-91, HTB-92 and HTB-94 STS cells remained unchanged. Furthermore, only 9cRA and tRA were capable of inducing apoptosis in HTB-82 and HTB-93 STS cells, whereas HTB-91, HTB-92 and HTB-94 STS cells did not undergo apoptosis under the influence of 9cRA or tRA. Retinoic acid receptor (RAR)-alpha and RAR-beta mRNA were not detectable by Northern blot analysis in the five STS cell lines, whereas mRNA for the universal retinoic acid receptor, RAR-gamma, was expressed in all STS cell lines indicating that retinoid resistance was not associated with a lack of RAR expression. Apoptosis was not induced by interferon-alpha or 13cRA in any of the five STS cell lines tested. Our results indicate that within the panel of tested STS cell lines, inhibition of proliferation and induction of apoptosis result from different mechanisms which differ in their dependence upon the presence of intact p53.

Apoptosis↗

Induction of immunomediated diseases by recombinant human granulocyte-macrophage colony-stimulating factor during cancer treatment?

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is widely used in the treatment or prevention of neutropenia induced by cytostatic regimens. Recent studies with this cytokine have shown several local and/or systemic side effects. We herein report on four patients with different tumor entities receiving GM-CSF as a part of their intensified cytostatic regimen. All four patients developed immune phenomena (sicca syndrome, seropositive arthralgia, hyperthyroidism, and pneumonitis, respectively) during or after subcutaneous treatment with GM-CSF. Pathologic alterations in immunologic serum parameters as well as histopathologic findings accompanied the clinical symptoms. These observations suggest that the therapeutic application of GM-CSF might be involved in the clinical emergence of autoimmune diseases.

Adult↗

Cytogenetic findings in colorectal cancer mirror multistep evolution of colorectal cancer.

Successful cytogenetic analysis was performed on tumor material from 26 patients with resectable colorectal cancer. 9 women and 17 men, aged 43 to 92 years, median 67 years. Clonal anomalies were found in twenty patients; five tumors showed mainly slight numerical changes such as trisomy 7 and loss of Y (2 cases). The remaining 15 tumors had highly complex karyotypes. The mainline was near diploid in six cases (5/6 tumors of the proximal colon), near triploid in four and near tetraploid in five tumors. Loss of chromosomes was most frequently observed with chromosomes 2, 5, 18, 20, and Y, the most frequently gained chromosomes were 7, 8, 13, 15, and X. Structural aberrations affected all chromosomes, except Y. The most frequently rearranged bands were 5q21, 7p15, 9p21, 13q11, 16p12, 17p13, 18q21, 21q11. Anomalies of chromosomes 5, 17, and 18 occurred concomitantly in 9/20 patients. All patients with deletions of 17p (n = 6) had near tetraploid karyotypes with high cell to cell variability and a median of nine structural aberrations (p < 0.007); four of them presented with parenchymal metastases at the time of surgery. Tumors of the proximal part of colon were with one exception diploid or near diploid, but no specific pattern of aberrations was detectable. However, it appears noteworthy that of the six patients with tumors of the ascending colon, three tumors had deletions at 16p12 and the affected patients had a short duration of survival. The tumor karyotypes of patients with parenchymal metastases revealed a trend to greater complexity of numerical and structural aberrations. Changes involving 8p22 or loss of chromosomes 8 were found in tumors of all parts of the colon and potentially associated with an unfavorable prognosis (4/7 decreased patients showed such changes).

Adult↗

Natural killer cell activity in long-term survivors of testicular cancer. Influence of cytostatic therapy and initial stage of disease.

BACKGROUND: Patients with testicular cancer can be cured by cisplatin-based chemotherapy in many cases. Thus, concern about possible late toxicities of treatment is warranted. METHODS: In this investigation, the absolute number of natural killer (NK) cells according to their CD56+ phenotype, NK cell activity, and antibody dependent cellular cytotoxicity (ADCC) were investigated in 29 patients with seminomas or nonseminomatous germ cell tumors (NSGCT) a median of 31 months (range, 5-73 months) after termination of chemotherapeutic treatment. RESULTS: No difference in the absolute number of NK cells, NK cell activity, and ADCC was found between patients with testicular cancer after either standard polychemotherapy consisting of bleomycin, etoposide, and cisplatin (BEP) or monotherapy with carboplatin and healthy control subjects. When patients were analyzed further using multivariate analysis, a significant (P < 0.05) detrimental influence of BEP polychemotherapy versus carboplatin monotherapy on NK cell activity was found. Moreover, NK cell activity also depended significantly (P < 0.05) on the time elapsed after chemotherapy was administered, but normalized with time. Because the absolute number of NK cells was not affected, is was assumed that polychemotherapy induced a functional defect. In a subanalysis of patients with NSGCTs, metastases at diagnosis resulted in a significant (p < 0.05) and persistent stimulation of NK cell activity but not of ADCC. CONCLUSION: Cytostatic chemotherapy in patients with testicular cancer did not lead to compromised lytic effector cell function as assessed by NK cell activity and ADCC. However, a short, time-dependent reduction was found that also depended on the intensity of chemotherapeutic treatment. This finding related to the observation of a long-lasting stimulus of NK cell activity by initial metastases in patients with NSGCTs.

Antibody-Dependent Cell Cytotoxicity↗

Treatment of experimental chronic osteomyelitis due to Staphylococcus aureus with ampicillin/sulbactam.

Ampicillin/sulbactam was used for the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 200 mg/kg (ampicillin) three times a day sterilized 40% of infected rabbit bones. The results of 4 weeks of treatment with ampicillin/sulbactam for chronic experimental staphylococcal osteomyelitis were comparable to those obtained previously with cephalothin and with oxacillin in previous studies and were not as good as those with clindamycin alone or combination therapy that included rifampin.

Ampicillin↗