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Biomedical subjects

A Mayer

Publications and source records attributed to A Mayer.

At least 109 records · Page 6Linked to original sources
PubMed1997

Immunohistochemical evaluation of cathepsin D expression in colorectal cancer.

Determination of cathepsin D has been proven to be prognostically relevant in breast cancer. Cathepsin D, a lysosomal proteinase, is suggested to be causally involved in tumor invasion. In this study we investigated cathepsin D expression immunohistochemically in 106 colorectal adenocarcinomas with the intention to evaluate its prognostic significance in this type of cancer. The majority of colorectal adenocarcinomas (93/106) stained positive for cathepsin D, while normal colon was almost completely negative. A trend toward stronger staining intensity was found in Dukes' stage C and D tumors (p < 0.1), but cathepsin D expression was found to have no influence on survival in this tumor type nor did it correlate with other known prognostic factors, e.g., histological differentiation, lymph vessel invasion, or rate of proliferation. Staining of lymph node metastases did not differ significantly from that of their primary tumors. Stronger staining intensity of tumor tissue in the neighborhood of inflammatory cells may be due to paracrine activation.

Adenocarcinoma↗
PubMed1997

The current surgical treatment of primary malignant melanoma of the skin.

In our Department, between 1991 and 1996, 132 patients, there of 87 male-45 female, average age of 48.2 years underwent surgery because of stage 1 (T2) to stage 3 melanoma that was located on the skin. None of patients suffered from early or in situ melanoma. Our retrospective study was based on those 94 patients who had been followed up by Department or dermatology-oncology in our medical centre. Surgery is still the primary treatment for cutaneous malignant melanoma. Thin melanomas (up to 2 mm in thickness) can be excised with 2 cm margins. Whether this is also true for thicker melanomas is not known and the only way to obtain more knowledge is to participate in prospective randomised studies. Elective lymph node dissection is associated with significant morbidity which includes lymphedema, wound complications and paresthesias of the extremity. For this reason we use an alternative operative approach uses selective lymphadenectomy with identification of the sentinel node.

Dermatologic Surgical Procedures↗
PubMed1997

Lymphadenectomy in gastrointestinal surgery for malignancy.

In a randomised study 25 patients with gastrointestinal surgery combined with extended lymphadenectomy (three field lymphadenectomy in case of esophageal cancer, D2 lymphadenectomy in case of gastric cancer) has been compared to the same number of patients with limited lymphadenectomy (D1). The operation time and the need for blood transfusion has increased in the extended lymphadenectomy group. The complication rate was more than doubled in the extended lymphadenectomy group, due to fluid or lymph collection, lymphatic edema, and infection. The mapping and staging was superior in extended lymphadenectomy group, but increased morbidity and mortality has been found in this group. However the favourable effect of extended lymphadenectomy on survival needs further long-term studies and proofs.

Blood Transfusion↗
PubMed1997

Stability of parenteral midazolam in an oral formulation.

Midazolam is increasingly being used for oral sedation in pediatric dentistry. Unfortunately, it is available only as a parenteral formulation in Canada and the United States. Preparation of the parenteral solution for oral use is not uniform and leads the clinician to question the stability of this drug when used in conjunction with these vehicles. Therefore, the purpose of this study was to investigate the chemical stability of parenteral midazolam as an oral formulation to determine its expiry date. This was evaluated using a validated stability-indicating liquid chromatographic method. Midazolam was diluted in orange-flavored syrup to yield concentrations of 0.35, 0.64, and 1.03 mg/ml and then stored at room temperature. Samples were drawn on each of 9 study days (0, 1, 2, 6, 7, 9, 13, 21, and 102) and chromatographed. On each study day, solutions were inspected visually for changes in color, clarity, and appearance of particulate matter. Midazolam concentrations were considered within acceptable limits if they were not less than 90% of the initial concentration. Over the 102-day study period, there was no significant change in concentration in any of the solutions. On day 102, the remaining midazolam was within 7% of the day zero concentration. Therefore, these formulations of midazolam are stable at room temperature for a period of 102 days and would be suitable for clinical use.

Administration, Oral↗
PubMed1996

Changes in apomorphine pharmacodynamics following repeated treatment in 6-hydroxydopamine-lesioned rats.

Rats with 6-OHDA lesions were repeatedly treated with apomorphine and dose-response relationships compared before and after treatment to better understand the pharmacological mechanisms which result in sensitization. A progressive increase in the magnitude and duration of rotational behavior was observed following repeated treatment and was associated with a nonparallel (upward) shift in apomorphine dose-response curves. These changes are inconsistent with simple shifts in drug potency, and instead are more consistent with changes in the ability of apomorphine to stimulate postsynaptic, striatal efferent pathways which result from repeated drug administration.

Animals↗
PubMed1996

Sec18p (NSF)-driven release of Sec17p (alpha-SNAP) can precede docking and fusion of yeast vacuoles.

S. cerevisiae inherits its vacuole by projecting vacuole-derived membrane vesicles and tubules into the bud, where they fuse to establish the daughter vacuole. This homotypic fusion event can be assayed in vitro. It requires Sec17p and Sec18p, the homologs of the mammalian alpha-SNAP and NSF, which cooperate in multiple steps of membrane trafficking. We now report that Sec17p, Sec18p, and ATP are only needed for an early stage of the reaction that results in Sec17p release. Sec17p and Sec18p actions precede, and are needed for, the step employing the Ras-like GTPase Ypt7p. Sec18p-driven release of Sec17p can even precede vacuole docking, as it can occur prior to mixing of vacuoles and is insensitive to vacuole concentration. Sec17p and Sec18p thus may function in a predocking stage of the reaction, rather than in bilayer fusion per se.

Adenosine Triphosphatases↗
PubMed1996

Active suppression of diabetes after oral administration of insulin is determined by antigen dosage.

We have previously demonstrated that feeding six-week-old female mice with 20 units of human insulin every 2 - 3 days for 15 or 30 days induced an active mechanism of suppression through the generation of regulatory T cells that reduced the number of successful diabetic transfers in irradiated NOD recipients. In the present study, we analyzed the effects of antigen dosage and the critical period of cell injection to obtain protection. The effects of the dose of insulin feeding were therefore compared during cotransfer experiments of 5 x 10(6) T cells from diabetic mice and 5 x 10(6) T cells from the spleen of mice receiving 10 units, 20 units, or 40 units of insulin or saline every 2 - 3 days for 15 days. Only T lymphocytes from mice fed with 20 units conferred active cellular protection during adoptive transfer with a significant delay in diabetes onset (p = 0.002). No significant difference was noticed during histological analysis of pancreatic glands, indicating tha insulitis was not prevented. However, mice receiving T lymphocytes from the 20 units of insulin-fed animals had a milder form of inflammation, with a significantly lower percentage of severely infiltrated islets. Injecting regulatory T cells 7 days and 14 days after iv injection of diabetogenic T cells did not modify the incidence curves of diabetes in the recipients, suggesting that cellular interactions and delay in cell trafficking were determinants. These results may have important clinical implications in humans. In conclusion, this study indicates the importance but also the limits of antigen therapy in type I diabetes. Antigen dosage is a critical element for active suppression. Such analysis is important to perform in humans before the initiation of a large-scale prevention trial in prediabetic individuals.

Administration, Oral↗
PubMed1996

HIV colonizing peripheral blood monocytes follows lymphocytic isolates in shifting from NSI to SI genotype.

Non-syncytium inducing (NSI) and syncytium inducing (SI) variants of human immunodeficiency virus (HIV) isolated from peripheral blood mononuclear cells (PBMC) could be definitely typed by sequence analysis of the env-gene V3 region. It was thus possible to compare the genotypes of viral variants isolated from PBMC and accompanying monocyte cultures and those derived directly from the patients' blood cells prior to cultivation. Within the investigated group of patients it was shown that HIV variants colonizing monocytes displayed a similar shift from NSI to SI as observed previously for PBMC, i.e. lymphocyte derived isolates. Lymphocytic SI variants could be isolated from the blood of patients, while simultaneously the predominant provirus in both blood and monocytic isolate was NSI. Consequently, we observed a delayed switch in the predominant provirus genotype found in blood which was associated with a synchronous change in the genotype of the corresponding monocytic isolate. The results show that monocytes/macrophages can be colonized by heterogeneous HIV variants in vivo and can therefore also function as carriers for the spread of highly virulent SI variants into the tissues.

Amino Acid Sequence↗
PubMed1996

Dermatolactone, a cytotoxic fungal sesquiterpene with a novel skeleton.

The nematicidal 5-pentyl-2-furaldehyde and the cytotoxic sesquiterpene dermatolactone were isolated from the extracts of an Ascomycete belonging to the Dermateaceae. The furan has previously been reported from the Basidiomycete Irpex lacteus, while dermatolactone is a new compound the structure of which was determined by spectrosocpic methods.

Animals↗
PubMed1996

Neoadjuvant chemotherapy (MVAC) in locally invasive bladder cancer.

In order to evaluate the efficacy of neoadjuvant chemotherapy in invasive urothelial carcinoma of the bladder a retrospective analysis was performed. 54 patients without distant metastases (T2-T3b, N0-X, M0) received 3 cycles of neoadjuvant chemotherapy according to the MVAC protocol (methotrexate, vinblastine, doxorubicin and cisplatin) after transurethral resection (TUR) followed by cystectomy. 52 patients had previously undergone cystectomy immediately after TUR. Complete histopathological remission was observed in 9 patients (17.3%) after TUR and in 17 patients (31.5%) after TUR+MVAC. Neoadjuvant MVAC resulted, therefore, in a 14% higher rate of complete remissions. The overall response to TUR was significantly improved by MVAC therapy. Downstaging by neoadjuvant chemotherapy was more readily achieved in initially low-stage tumours (T2: 44.4% and 30.8%, T3a: 47.1% and 19%, T3b: 5.3% and 5.5% in patients receiving TUR+MVAC and TUR alone, respectively). Overall survival did not differ significantly between both groups. Patients who were successfully downstaged to pT0 had a significantly better prognosis, and patients resistant to chemotherapy had the poorest prognosis, showing the shortest survival. In conclusion, histopathological response at cystectomy was improved by neoadjuvant MVAC chemotherapy after TUR and can be expected to be prognostically relevant in those patients who can be downstaged to T0, although overall survival failed to be significantly increased in this relatively small patient sample.

Aged↗
PubMed1996

Distribution of HIV-1 subtypes seen in an AIDS clinic in Sao Paulo City, Brazil.

OBJECTIVE: To determine the distribution of HIV-1 subtypes in Sao Paulo, Brazil. METHODS: Samples were obtained from 80 consecutive HIV-1-infected individuals attending the Immunodeficiency Clinic at the University of Sao Paulo in 1993. Peripheral blood mononuclear cells (PBMC) were separated by Ficoll-Hypaque gradient and a portion was used for routine CD4 counts; the remainder were frozen. PBMC were proteinase-K-digested and DNA-purified by organic extraction. Samples were amplified for the env region of HIV, and envelope sequence subtypes determined by heteroduplex mobility analysis using prototypic subtypes as references. A subset of these were also sequenced through the C2-V3 region of env. RESULTS: A total 69 of 80 samples yielded env polymerase chain reaction product enabling subtype determination; samples that did not amplify were those with low DNA yields. Among 12 injecting drug users (IDU) or sexual partners of IDU, four were typed as clade F and eight as clade B. Forty-three homosexual men or female sexual partners of bisexual men were typed as clade B. The 14 additional cases without known risk factors were typed as clade B. CONCLUSION: These data suggest that subtype F is related to injecting drug use in Brazil.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Cell-free reconstitution of the transport of viral glycoproteins from the TGN to the basolateral plasma membrane of MDCK cells.

An in vitro system to study the transport of plasma membrane proteins from the TGN to the basolateral plasma membrane of polarized MDCK cells has been developed in which purified cell fractions are combined and transport between them is studied under controlled conditions. In this system, a donor Golgi fraction derived from VSV or influenza virus-infected MDCK cells, in which 35S-labeled viral glycoproteins were allowed to accumulate in the TGN during a low temperature block, is incubated with purified immobilized basolateral plasma membranes that have their cytoplasmic face exposed and are obtained by shearing-lysis of MDCK monolayers grown on cytodex beads. Approximately 15-30% of the labeled glycoprotein molecules are transferred from the Golgi fraction to the acceptor plasma membranes and are recovered with the sedimentable (1 g) beads. Transport is temperature, energy and cytosol dependent, and is abolished by alkylation of SH groups and inhibited by the presence of GTP-gamma-S, which implicates GTP-binding proteins and the requirement for GTP hydrolysis in one or more stages of the transport process. Endo H-resistant glycoprotein molecules that had traversed the medial region of the Golgi apparatus are preferentially transported and their luminal domains become accessible to proteases, indicating that membrane fusion with the plasma membrane takes place in the in vitro system. Mild proteolysis of the donor or acceptor membranes abolishes transport, suggesting that protein molecules exposed on the surface of these membranes are involved in the formation and consumption of transport intermediates, possibly as addressing and docking proteins, respectively. Surprisingly, both VSV-G and influenza HA were transported with equal efficiencies to the basolateral acceptor membranes. However, low concentrations of a microtubular protein fraction preferentially inhibited the transport of HA, although this effect was not abolished by microtubule depolymerizing agents. This system shows great promise for elucidating the mechanisms that effect the proper sorting of plasma membrane proteins in the TGN and their subsequent targeting to the appropriate acceptor membrane.

Animals↗
PubMed1996

Clinical experience with the Ben-Sira teledioptric system for use in age-related macular degeneration.

Hanita-Ben-Sira has recently developed a bifocal optical implant with central hyperminus and peripheral positive components that is used in conjunction with specially constructed spectacles to improve visual performance in patients with age-related macular degeneration. The Ben-Sira teledioptric system was evaluated in 17 patients. It produces a magnified image of high and improved resolution and an enlargement of the visual field. It is easy to use and increases the reading distances.

Aged↗
PubMed1995

[Recombinant human erythropoietin in the treatment of anemic patients undergoing chemotherapy for cancer].

Twenty-seven anemic patients with malignant tumour who received chemotherapy were treated with recombinant human erythropoietin (r-HuEPO). The objective of this study was to evaluate the effect of r-huEPO on hematologic and quality of life parameters as well as on transfusion requirement in patients with anemia secondary to cancer and cyclic chemotherapy. Patient population was allocated into two groups based on the chemotherapeutic regimens: 1. cisplatin containing and 2, non cisplatin containing regimen. Using 2 g/dl increase in haemoglobin levels as the criteria for response, twenty women responded to r-huEPO treatment. The response was more marked in the cisplatin group. R-huEPO treatment saved transfusion in both groups. Again, less patients required transfusion among those treated with cisplatin. There was a marked improvement in the quality of life which was more pronounced in patients who responded to r-huEPO treatment and in those receiving non cisplatin chemotherapy. No serious adverse experiences occurred. In conclusion, two third of patients with anemia secondary to cancer and cyclic chemotherapy can be effectively treated with r-huEPO. R-huEPO treatment invariably saves transfusion and is highly effective in improving quality of life. Adverse reaction is exceptional.

Anemia↗