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Biomedical subjects

P Forrer

Publications and source records attributed to P Forrer.

17 recordsLinked to original sources
PubMed2002

Primary breast lymphoma, contralateral breast cancer, and bilateral Brenner tumors of the ovary.

BACKGROUND: Primary lymphoma of the breast is an unusual clinical entity. Its presence with invasive breast cancer and bilateral Brenner tumors of the ovary is very rare. CASE: We report a 62-year-old woman referred for further evaluation of a palpable mass in her breast. She was diagnosed and treated for simultaneous primary lymphoma of the right breast, contralateral invasive ductal carcinoma, and bilateral Brenner tumors of the ovary. One year after treatment, she is free of recurrence or progression. CONCLUSION: Compared with breast carcinoma, primary breast lymphoma is a rare disease but should be considered in the differential diagnosis of breast masses. The presence of both breast malignancies presents a challenge in treatment decisions.

Breast Neoplasms↗
PubMed2002

Vinorelbine in androgen-independent metastatic prostatic carcinoma--a phase II study.

The purpose of this study was to evaluate the efficacy of vinorelbine treatment in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score for the subgroup of patients with pain), as well as its toxicity in patients with progressive metastatic androgen-independent prostatic carcinoma. 44 patients with prostatic carcinoma progressing after orchiectomy or during treatment with hormonal agents were treated with vinorelbine at a dose of 30 mg/m(2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle. Inclusion criteria were metastatic progressive prostatic carcinoma with prostate-specific antigen (PSA) serum levels >/=3 x upper limit of normal, World Health Organization (WHO) performance status </=2, age <85 years and adequate bone marrow, liver and renal functions. Treatment was continued until progression or a maximum of 12 cycles. Treatment was delayed for a week if haematological toxicity grade >/=2 was observed on the day of scheduled vinorelbine administration. 9 patients received less than three cycles, 6 due to rapid tumour progression. Treatment at day 1 had to be delayed in 13.7% of 183 cycles. Treatment at day 8 had to be omitted in 19.7% of all cycles. Grade >/=3 granulocytopenia occurred in 18% of patients. 4 patients had severe constipation. In 7 patients (15.9%, Confidence Interval (CI) 6.6-30.1%), a PSA response (>/=50% reduction of PSA levels) was observed. Among 8 patients with measurable disease, 3 had partial remission and 1 no change. Median time to PSA progression in 43 assessable patients was 11.9 weeks (range 3-52 weeks). Median duration of PSA response was 14 weeks (9-30 weeks). Clinical benefit was seen in 7 of 31 cases (23%) with baseline pain, there was no association with PSA response. Vinorelbine is a fairly well tolerated drug with a moderate single agent activity in patients with androgen-refractory prostate cancer.

Aged↗
PubMed2001

In vitro display technologies: novel developments and applications.

In vitro display techniques are powerful tools to select polypeptide binders against various target molecules. Novel applications include maturation of protein affinity and stability, selection for enzymatic activity, and the display of cDNA and random polypeptide libraries. Taken together, these display techniques have great potential for biotechnological, medical and proteomic applications.

Binding Sites↗
PubMed2000

Novel fold and capsid-binding properties of the lambda-phage display platform protein gpD.

The crystal structure of gpD, the capsid-stabilizing protein of bacteriophage lambda, was solved at 1.1 A resolution. Data were obtained from twinned crystals in space group P21 and refined with anisotropic temperature factors to an R-factor of 0.098 (Rfree = 0. 132). GpD (109 residues) has a novel fold with an unusually low content of regular secondary structure. Noncrystallographic trimers with substantial intersubunit interfaces were observed. The C-termini are well ordered and located on one side of the trimer, relatively far from its three-fold axis. The N-termini are disordered up to Ser 15, which is close to the three-fold axis and on the same side as the C-termini. A density map of the icosahedral viral capsid at 15 A resolution, obtained by cryo-electron microscopy and image reconstruction, reveals gpD trimers, seemingly indistinguishable from the ones seen in the crystals, at all three-fold sites. The map further reveals that the side of the trimer that binds to the capsid is the side on which both termini reside. Despite this orientation of the gpD trimer, fusion proteins connected by linker peptides to either terminus bind to the capsid, allowing protein and peptide display.

Amino Acid Sequence↗
PubMed1999

Beyond binding: using phage display to select for structure, folding and enzymatic activity in proteins.

Phage display of a wide range of polypeptides has been increasingly used to identify novel molecules with useful binding properties for research, medical and industrial applications. Recent developments include methods for the selection of stabilized variants of a protein, the selection of regulatable enzymes and promising strategies for the selection and evolution of protein catalysts.

Bacteriophages↗
PubMed1999

Enzyme-linked immunosorbent assay for the measurement of JNK activity in cell extracts.

A colorimetric enzyme-linked immunosorbent assay (ELISA) for the measurement of kinase activity of c-Jun N-terminal kinases (JNKs) in cell extracts is described. The assay involves passive immobilisation of the substrate GST-cJun on the surface of a microtiter plate, selection of JNK protein kinases directly in substrate-coated wells, kinase reaction, and detection of substrate phosphorylation by a phosphoepitope-specific antibody. The ability of this assay to selectively measure JNK activity relies on the high-affinity interaction between JNKs and c-Jun. Accordingly, we found that JNKs could be captured on the microtiter plate surface through binding to the immobilised GST-cJun. Moreover, JNKs retained the specificity of their interaction with and phosphorylation of c-Jun with respect to the dependence on both intact docking domain and the dimerisation state of c-Jun. This novel procedure represents a marked improvement on conventional radioactive assays in terms of sensitivity, accuracy of evaluation, low time consumption, high throughput and amenability to automation. It is expected to be useful forthe acceleration and facilitation of JNK activity measurement in cell extracts, in particular for large-scale screening of clinical samples.

3T3 Cells↗
PubMed1998

High-level expression of soluble heterologous proteins in the cytoplasm of Escherichia coli by fusion to the bacteriophage lambda head protein D.

The bacteriophage Lambda head protein D (gpD) is a small major capsid protein (110aa; 11.6kDa; pI=5.68, devoid of cysteine residues) that is essential for stable head morphogenesis. We found that a His-tagged derivative of gpD (gpHD) is a monomeric protein with efficient expression properties and high resistance towards thermally induced irreversible aggregation. In addition, gpHD can be used as a fusion partner for high-level expression of soluble heterologous proteins in the cytoplasm of Escherichia coli. Its broad utility is illustrated by the production of various mammalian proteins by fusion to its C-terminus. As a fusion partner, gpHD is thought to mediate optimal translation initiation while reducing inclusion body formation and protein degradation. In addition, it provides a His-tag for simple purification. gpHD may act as a 'cytoplasmic anchor' by keeping its unfolded fusion partner in solution, thereby providing more time for proper folding. An ever-increasing number of open reading frames (ORFs) are being identified in the various genome sequencing programs. gpHD has the potential to be harnessed for the development of highly efficient cytoplasmic expression systems that might contribute to the production and characterization of these novel polypeptides. Protein D is also an established fusion partner for phage display. It thus presents the attractive opportunity of coupling the selection of heterologous proteins from a phage library to their subsequent high-level expression.

Bacteriophage lambda↗
PubMed1993

Stereo-microvision. Development of an opto-electronic operating microscope.

A novel opto-electronic operating microscope has been designed and clinically tested. It consists of a small camera microscope, a central electronic unit, and a stereoscopic video monitor. Advanced miniaturization permitted ergonomics superior to those of conventional optomechanical microscopes. Electronic imaging facilitates coupling to an ultrasound navigation system which enables the neurosurgeon to verify the location of the focus in real time, correlated with CT and MRI pictures. A fully computerized, digital operating microscope will now be developed based on this prototype.

Brain Diseases↗
PubMed1977

[Kinetics and regulation of granulocytopoiesis (author's transl)].

The present survey of the development of the granulocytes consists of two parts. In the first section the different stages of granulopoiesis are discussed with special regard to the stem cells. In the second one the regulation of the granulopoiesis and the different factors taking part in the homeostasis of the granulocytes are examined. Emphasis is placed upon the colony stimulating activity" (CSA) previously tested in different situations of stress in relationship to the granulopoietic system. In a separate chapter some marked clinical syndromes are discussed which accompany disorders of granulocyte-homeostasis. The pathogenesis of leukaemia is reviewed.

Agranulocytosis↗
PubMedDate not supplied

Enzyme-linked immunosorbent assay for measurement of JNK, ERK, and p38 kinase activities.

A rapid enzyme-linked immunosorbent assay for the enzyme activity measurement of three well-known mitogen-activated protein (MAP) kinases, JNK2, ERK2, and p38 is described. The assay involves immobilization of the respective kinase substrates c-Jun, Elk1, or ATF2 on microtiter plates, addition of the kinase reaction mixture, and measurement of substrate phosphorylation using phospho-epitope-specific antibodies. This novel procedure represents a marked improvement to conventional radioactive MAP kinase assays in terms of quantification, precision, performance at physiological ATP concentration, high throughput, time consumption and amenability to automation. In addition to the standard solid phase assay using plastic-bound protein substrates, we developed an alternative solution phase protocol using soluble protein substrates. By comparing the results of the two assays, we found that MAP kinases retained much of their substrate specificity in the phosphorylation of immobilized protein substrates. Interestingly, we observed a strong preference of JNK2 and p38 for the phosphorylation of dimeric over monomeric substrates. We further characterized the kinase inhibitory activity of olomoucine, staurosporine, and SB 203580 for JNK2, ERK2, and p38. Taken together, this assay could assist in the biochemical characterization of MAP kinases and in identifying potent and specific inhibitors of these enzymes.

3T3 Cells↗