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Biomedical subjects

E Weiss

Publications and source records attributed to E Weiss.

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

Association of olanzapine-induced weight gain with an increase in body fat.

OBJECTIVE: The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia. METHOD: The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period. RESULTS: A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change. CONCLUSIONS: In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.

Adipose Tissue↗
PubMed2001

Radiotherapy combined with simultaneous chemotherapy with mitomycin-C and 5-fluorouracil for inoperable head and neck cancer.

The feasibility and effectiveness of a combined chemoradiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. From March 1995 to June 1998, 35 patients with advanced squamous cell carcinoma of the head and neck were treated with a continuous intravenous infusion of 5-fluorouracil (600 mg m-2 24 h-1 for Days 1 to 5 (120 h)) and mitomycin-C (10 mg m-2 intravenously) on Day 5 during the first week of radiotherapy and on Day 36. 31 patients had stage IV disease; 4 patients had stage III; and 1 patient had stage II. Patient ages ranged from 42-69 years (median 56.7 years). The tumours involved were as follows: oral cavity (n = 11); oropharynx (n = 14); hypopharynx/larynx (n = 10). Radiotherapy was delivered to a total dose of 70 Gy with conventional fractionation (2 Gy per fraction, five times a week). Chemotherapy was well tolerated and all patients received the intended dose. Mild nausea occurred in five patients. After a mean follow-up of 21 months (range 10-44 months), 8 (23%) patients remain alive. A complete response was seen in 28 (80%) patients. When a recurrence appeared, it was within the first year after treatment. 1- and 2-year overall survival rates were 46% and 23%, respectively. Grade 3 mucositis occurred in 17% of patients. Grade 1-2 thrombopaenia occurred in 3 (9%) patients, grade > 2 leukopaenia in 4 (11%) patients, and grade > or = 2 anaemia in 3 (9%) patients. We observed a treatment interruption of maximum 1 week for six patients owing to mucositis. Febrile neutropaenia or aplasia were not observed. The concomitant use of 5-fluorouracil, mitomycin-C and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. This protocol showed good locoregional response with a very low toxicity profile.

Adult↗
PubMed2001

The rescue by phage display of human Fabs to gp120 HIV-1 glycoprotein using EBV transformed lymphocytes.

Human hybridomas secreting monoclonal antibodies in a stable manner are difficult to develop. The main difficulties are the restricted techniques for B-cell immortalization, the low number of sensitized B cells in peripheral blood, and the impossibility, for ethical reasons, to immunize humans with most antigens. Phage display has proved to be a powerful method for the generation of recombinant antibody fragments. This technology relies on the construction of recombinant Fab or scFv libraries and their display on phage M13. In order to rescue unstable B-cell clones secreting human antibodies we set up a method for the selection by phage display of human IgG fragments from Epstein-Barr virus (EBV)-transformed clones and applied it to the selection by phage display of Fabs directed against HIV-1 gp120, using a seropositive blood sample. The approach combines B-cell transformation by EBV of peripheral blood lymphocytes from a seropositive donor, preselection of specific IgG anti-gp120 producing clones, and the construction of a targeted human antibody library. In this library the percentage of heavy and light chain coding sequences expressed in Escherichia coli, amplified by a set of specific 5' primers for different antibody germ lines, was similar to that observed with the original untransformed B-cell sample. One round of panning was sufficient for the rescue of three Fabs specific for HIV-1 gp120 protein, which proves the efficiency of this technique.

Amino Acid Sequence↗
PubMed2001

Accessibility of primary care services in safety net clinics in New York City.

OBJECTIVES: This study analyzed data from a survey of New York City ambulatory care facilities to determine primary care accessibility for low-income patients, as evidenced by the availability of enabling services, after-hours coverage, and policies for serving the uninsured. METHODS: Ambulatory care facilities were surveyed in 1997, and analysis was performed on a set of measures related to access to care. Only sites that provided comprehensive primary care services were included in the analysis. For comparison, site were classified by sponsorship (public, nonprofit voluntary hospital, federally qualified health center, non-hospital-sponsored community health center). RESULTS: Publicly sponsored sites and federally qualified health center sites showed the strongest performance across nearly all the measures of accessibility that were examined. CONCLUSIONS: As safety net clinics confront the financial strain of implementing mandatory Medicaid managed care while also dealing with declining Medicaid caseloads and increasing numbers of uninsured, their ability to sustain the policies and services that support primary care accessibility may be threatened.

Communication Barriers↗
PubMed2001

Mohs micrographic surgery of the nail unit and squamous cell carcinoma.

The nail unit can be a challenging anatomic location for surgical removal of neoplasms. Although uncommon, malignancies do affect this specialized epithelial structure. In particular, Bowen's disease and more invasive squamous cell carcinoma (SCC) are the most common neoplasms to affect the nail unit and surrounding structures. Other neoplasms such as basal cell carcinoma and malignant melanoma can also affect the nail unit, but less frequently, and will not be discussed in the scope of this review. Mohs micrographic surgery continues to be the treatment of choice because of the procedure's tissue-sparing qualities. A clear understanding of the anatomy and the histology of the nail unit, a review of the technique of Mohs surgery of the nail anatomy, as well as a review of the literature are presented.

Carcinoma, Squamous Cell↗
PubMed2000

Acid catalyzed Michael additions to artemisitene.

A series of 14-substituted-artemisinin and 9-epiartemisinin derivatives was prepared by a titanium-tetrachloride catalyzed addition of trimethylsilyl enol ethers to artemisitene. Several compounds were four to seven times more active than artemisinin against Plasmodium falciparum.

Artemisinins↗
PubMed2000

HPV oncoprotein E6 is a structure-dependent DNA-binding protein that recognizes four-way junctions.

E6 is an oncoprotein implicated in cervical cancers, produced by "high-risk" human papillomaviruses. E6 is thought to promote tumorigenesis by stimulating cellular degradation of the tumour suppressor p53, but it might display other activities. Sequence similarity was recently detected between E6 and endonuclease VII, a protein of phage T4 that recognizes and cleaves four-way DNA junctions. Here, we purified recombinant E6 proteins and demonstrated that high-risk E6 s bind selectively to four-way junctions in a structure-dependent manner. Several residues in the C-terminal zinc-binding domain, the region of E6 similar to endonuclease VII, are necessary for the junction-binding activity. E6 binds to the junction as a monomer. Comparative electrophoresis shows that E6-bound junctions migrate in an extended square conformation. Magnesium inhibits the electrophoretic migration of the complexes but does not seem to influence their formation at equilibrium. This work is the first demonstration of specific binding of purified active E6 to a well-characterized DNA ligand, and suggests new modes of action of E6 in oncogenesis.

Amino Acid Sequence↗
PubMed2000

Production of fluorescent single-chain antibody fragments in Escherichia coli.

We describe a novel vector-host system suitable for the efficient preparation of fluorescent single-chain antibody Fv fragments (scFv) in Escherichia coli. The previously described pscFv1F4 vector used for the bacterial expression of functional scFv to the E6 protein of human papillomavirus type 16 was modified by appending to its C-terminus the green fluorescent protein (GFP). The expression of the scFv1F4-GFP fusion proteins was monitored by analyzing of the typical GFP fluorescence of the transformed cells under UV illumination. The brightest signal was obtained when scFv1F4 was linked to the cycle 3 GFP variant (GFPuv) and expressed in the cytoplasm of AD494(DE3) bacteria under control of the arabinose promoter. Although the scFv1F4 expressed under these conditions did not contain disulfide bridges, about 1% of the molecules were able to bind antigen. Fluorescence analysis of antigen-coated agarose beads incubated with the cytoplasmic scFv-GFP complexes showed that a similar proportion of fusions retained both E6-binding and green-light-emitting activities. The scFv1F4-GFPuv molecules were purified by affinity chromatography and successfully used to detect viral E6 protein in transfected COS cells by fluorescence microscopy. When an anti-beta-galactosidase scFv, which had previously been adapted to cytoplasmic expression at high levels, was used in this system, it was possible to produce large amounts of functional fluorescent antibody fragments. This indicates that these labeled scFvs may have many applications in fluorescence-based single-step immunoassays.

Animals↗
PubMed2000

Rhabdoid tumors of the central nervous system.

Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor's biology and possible strategies of treatment.

Adolescent↗
PubMed2000

Do prior abdominal operations alter the outcome of laparoscopically assisted right hemicolectomy?

BACKGROUND: Adhesions can increase the difficulty of both laparoscopic surgery and laparotomy. The aim of this study was to compare the results of laparoscopically assisted right hemicolectomy in patients after prior abdominal operations (PAOs) with the results in patients without prior abdominal operations (NPAOs). METHODS: Between August 1991 and September 1998, 85 patients underwent laparoscopically assisted right hemicolectomy. The Mann-Whitney test or Fisher's exact test was used for statistical analysis. RESULTS: In this study, 36 patients (21 women and 15 men), with an average age of 57.5 years (range, 15-87 years) had undergone a mean of 1.25 (range, 1 to 3) PAOs, whereas 49 patients (20 women and 29 men), with an average age of 60.0 years (range, 16 to 87 years) (p = 0.44) had undergone NPAOs. Overall in the PAO and NPAO groups, respectively, there were no significant differences in the incidence of intraoperative complications (3 versus 4; p = 1.0). The mean operative time was 151 min (range, 90 to 260 min) versus 148 min (range, 70 to 270 min) (p = 0.66), and the mean length of stay was 6. 8 days (range, 3 to 18 days) versus 7.6 days (range, 3 to 19 days) (p = 0.13). The procedure was converted to laparotomy (p = 0.754) for six patients in the PAO group (5 because of adhesions) and 6 patients in the NPAO-group (1 because of adhesions; p = 0.078). In the PAO group 17 patients (47%) had 22 postoperative complications: 11 general medical and 4 wound-related complications. Seven patients (19%) had prolonged postoperative ileus. In the NPAO-group 18 patients (38%) had a total of 22 complications: 7 general medical problems, 6 wound-related complications, and 8 prolonged postoperative ileus, none of which were statistically significant. One patient in the NPAO group had an anastomotic leak. During a mean follow-up period of 41 months (range, 3 to 89 months), three patients in the PAO group and four in the NPAO group developed incisional hernias. CONCLUSIONS: Although there is a trend toward more conversions because of adhesions in patients with a history of prior abdominal operations (p = 0.078), no increase in morbidity resulted. Therefore, laparoscopically assisted right hemicolectomy can be offered to patients with PAO, whose rate of adhesions can be expected to equal that of patients with NPAO.

Abdomen↗
PubMed2000

The use of rectal ultrasound for the correct diagnosis and treatment of rectal villous tumors.

BACKGROUND: One of the difficulties associated with surgery for rectal villous tumors (RVT) is the finding of invasive adenocarcinoma after transanal excision (TAE) and the possible need for more radical procedures or adjuvant therapy. Improved preoperative evaluation may eliminate this dilemma. The aim of our study was to evaluate the role of transrectal ultrasound (TRUS) in establishing the correct diagnosis of RVT. METHODS: All patients with biopsy proven RVT, who were referred for TAE, underwent preoperative TRUS in addition to the routine evaluation. If invasion beyond the submucosa was suspected by TRUS, multiple biopsies were taken before any surgical intervention in order to exclude invasive cancer. If no invasion was noted, biopsies were avoided and a TAE was performed. The final pathology results were compared with both the preoperative diagnosis and TRUS results. RESULTS: Thirty-five patients (19 female, 16 male; mean age 67.5 years, range 36 to 88) were studied. The mean distance of the distal extent of the lesion above the anal verge was 5.8 cm (1.5 to 6). In 27 patients, the tumor was limited to the submucosa (uT0, uT1) on TRUS and, therefore, TAE was performed. In 26 of 27 patients (96%), pathology examination confirmed the presence of RVT without evidence of malignancy. One patient was found to have invasion of the muscularis propria and required postoperative radiation therapy. In 8 patients (23%), TRUS showed extension beyond the submucosa; 3 of these patients had uT2 lesions, 4 had uT3 tumors, and 1 had perirectal nodes. These 8 patients underwent repeated biopsies with the finding of invasive adenocarcinoma in 7. Two patients underwent abdominoperineal resection, 3 had a low anterior resection, and 3 had a TAE. Final pathology confirmed the preoperative diagnosis of invasive adenocarcinoma in 7 patients. In the 1 patient with a uT2 lesion and negative biopsies, the final diagnosis was RVT with no evidence of malignancy. CONCLUSIONS: Preoperative TRUS provides an accurate diagnosis of RVT. In conjunction with TRUS-directed biopsies, directed management of these tumors could be achieved.

Adenoma, Villous↗
PubMed2000

Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin.

A series of N-substituted 11-azaartemisinins were prepared in high yield employing base-catalyzed additions to an amide nitrogen of olefins and terminal acetylenes conjugated with electron withdrawing groups (EWGs). When the terminal acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or carbonyl groups, the E-adducts resulted. A mixture of E- and Z-adducts were obtained when the EWG was a nitrile. In vitro antimalarial activities of each compound were determined against two drug-resistant strains of Plasmodium falciparum. Many of the compounds prepared were several times more active than artemisinin.

Animals↗
PubMed2000

Bypassing hybridoma technology: HLA-C reactive human single-chain antibody fragments (scFv) derived from a synthetic phage display library (HuCAL) and their potential to discriminate HLA class I specificities.

The generation of discriminative, monospecific anti-HLA antibodies used to be a difficult endeavor. Phage display technology, using single-chain antibody fragments (scFv) offers a powerful alternative obtaining target-specific, genetically stable reagents. Most of scFv obtained to date have been enriched by panning phage libraries to solid-phase coupled antigens. In the present study, HLA-C-specific scFv were isolated using a synthetic phage library in combination with a Cw*0602 overexpressing cell line. ScFv from this procedure precipitated HLA-Cw*0602 heavy chains from whole cell lysates. Flow cytometry analysis revealed that scFv stained HLA-Cw*0602-positive cells, but not cells expressing HLA alleles Cw*0302, Cw*0802, A*0201, B*2705, or Gm1*01011, indicating the specificity of scFv. Similarly they showed an ability to discriminate Cw*0602-positive from Cw*0602-negative peripheral blood lymphocytes (PBL). The results of our study demonstrate the feasibility to genetically engineer single-chain HLA-class I-specific antibodies, by phage display technology. This approach might be a valuable tool to develop a broad range of novel monospecific antibodies against HLA-class I specificities.

Alleles↗
PubMed2000

Off-label use of antipsychotic drugs.

Despite the fact that most antipsychotics have only been formally evaluated for the treatment of schizophreniform disorder, schizophrenia, mania, and schizoaffective disorder (defined as "classical indications"), antipsychotics are widely used for the treatment of a broad range of symptoms and disorders. In this study, 173 patients who were having their prescriptions for antipsychotics filled at local pharmacies were interviewed. In 115 patients (66.5%), an antipsychotic was prescribed for off-label indications. Patients most often stated that they took antipsychotics as a tranquilizer or an anxiolytic. Neither gender, education, duration of treatment, nor efficacy of treatment showed an influence on the prescription practices for antipsychotics. In contrast, family status and side effects showed a significant influence. A classical indication was more often found in married and widowed patients than in unmarried or divorced ones. Patients in whom antipsychotics were prescribed for the treatment of schizophrenia, schizophreniform disorder, mania, or schizoaffective disorder experienced side effects more often than others. Age was also important for the indication of antipsychotics. Classical indications of antipsychotics were most often found in patients aged 30 to 49 years. In older patients (49-70 years), antipsychotics were almost exclusively used for off-label indications. In classical indications, clozapine was used more frequently (50%) than other antipsychotics. Melperone was primarily prescribed for off-label use.

Adolescent↗
PubMed2000

Effect of various mixing ratios on antibacterial properties and hardness of endodontic sealers.

Most chemically cured two-component dental materials, including endodontic sealers, are marketed with mixing instructions but with no strict mixing ratios. The present study evaluated the antibacterial properties and hardness of three endodontic sealers: Roth's cement (RC), CRCS, and AH26, mixed to four controlled consistencies within the range of the manufacturer recommendations. Using Enterococcus faecalis as the test microorganism, antibacterial activity was evaluated by agar diffusion and direct contact test. Surface hardness of sealers with the same consistency was evaluated on week-old specimens by the Knoop Hardness Number tester. In the agar diffusion test, light consistency of RC showed larger zones of inhibition than heavier consistency, whereas no significant differences were found with AH26 or CRCS. In the direct contact test, RC and CRCS exhibited complete inhibition of bacterial growth at all consistencies, whereas AH26 with the heavier consistencies did not inhibit bacterial growth at 24 h samples. The hardness of AH26 and CRCS was significantly lower with lighter consistencies. It is concluded that endodontic sealers possess different antibacterial and physical properties according to their mixing consistencies.

Anti-Infective Agents, Local↗
PubMed1999

In vivo biotinylated recombinant antibodies: high efficiency of labelling and application to the cloning of active anti-human IgG1 Fab fragments.

In vivo biotinylation of antibody fragments with a gene fusion approach is a realistic alternative to conventional in vitro chemical labelling. We have previously reported the construction of a vector system suitable for the bacterial expression of the binding fragment of antibody (Fab) genetically linked to the C-terminal domain of Escherichia Coli biotin carboxy carrier protein (BCCP*). A minor fraction of the expressed hybrids was biotinylated in vivo and therefore able to interact with streptavidin. We now show that the large majority of bacterially-expressed Fab-BCCP* fusions are labelled with biotin when plasmid-encoded biotin holoenzyme synthetase (BirA) is co-expressed. The yield of biotinylated Fab is maximal when overexpression of BirA is driven by a second compatible plasmid. We took advantage of this property to develop a novel filter assay for the rapid identification of recombinant Fab reacting with immunoglobulin. Starting with total RNA of two newly established murine hybridoma cell lines producing anti-human IgG1 antibodies, we selected in a single experiment the bacterial clones that expressed in vivo biotinylated anti-IgG1 Fab. Sequence analysis of the isolated Fabs showed that they did not derive from a single B clone. In addition, we found that these recombinant Fabs labelled with biotin in vivo are useful for the specific detection of human IgG1 by a solid-phase immunoassay.

Acetyl-CoA Carboxylase↗