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Biomedical subjects

J Post

Publications and source records attributed to J Post.

At least 19 recordsLinked to original sources
PubMed1996

Metastatic uveal melanoma. A morphologic and immunohistochemical analysis.

BACKGROUND: Uveal melanoma often metastasizes late and preferentially to the liver, in contrast to cutaneous melanoma. The objective of the current study was to evaluate the histopathologic and immunohistochemical changes in primary uveal melanomas and their corresponding metastases. METHODS: The morphology and immunohistochemical reactivity for the melanoma-associated antibodies HMB-45, S-100 protein, and NKI-C3 were assessed for 29 primary uveal melanomas and their corresponding metastatses. RESULTS: A significant difference in cell type of the primary and the metastatic uveal melanoma was found (P = 0.0001). The metastases derived from the 29 patient's revealed 82.5% epithelioid or nonclassifiable cells. Positive staining of the primary uvea melanomas and their metastases was found to be 93% and 91%, respectively, for HMB-45, 80% and 66%, respectively, for S-100, and 56% and 71%, respectively, for NKI-C3. CONCLUSIONS: Metastases of uveal melanomas are comprised of a higher grade of malignant cell types. Nonclassifiable cells can be observed in 40% of metastatic lesions. In the current study, HMB-45 proved to be the most sensitive immunohistochemical marker in the analysis of metastatic uveal melanoma and should be used as part of a panel of monoclonal antibodies in the analysis of any metastatic tumor of unknown origin.

Antigens, Neoplasm↗
PubMed1996

Efficacy and toxicity of plasma-cell-reactive monoclonal antibodies B-B2 and B-B4 and their immunotoxins.

Immunotherapy based on the delivery of toxic agents to the tumor site using monoclonal antibodies (mAb) may be a promising modality in the treatment of hematological malignancies. In the selection of mAb, both for ex vivo but even more for in vivo therapy, not only their reactivity to the neoplastic cells should be considered, but also reactivity to other body constituents. Here we describe the screening of two human plasma-cell-reactive mAb B-B2 and B-B4, which may be used for immunotherapy of multiple myeloma. Cross-reactivity of B-B2 and B-B4 was determined by immunohistochemistry on a series of tissues. This revealed for both B-B2 and B-B4 a strong staining of epithelial cells in various organs, e.g. lung, liver, skin, kidney and gut, while only a weak and diffuse staining was seen with endothelial cells. In bone marrow reactivity was only found with plasma cells and not with hemopoietic precursors (CD34+ cells). Immunotoxins from B-B2 and B-B4 were constructed by coupling them to the plant-derived ribosome-inactivating protein saporin. Both B-B2 and B-B4 immunotoxins appeared to be efficient in specific inhibition of protein synthesis in plasma cell lines (IC50 respectively 1 nM and 0.1 nm). The immunotoxins were also tested on epithelial cell line A431, on liver cell line HepG2 and on human umbilical vein endothelial cells. The epithelial cell line A431 was reactive with both B-B2 and B-B4, but was only inhibited by B-B4 immunotoxin. Cell line HepG2 was reactive with both mAb, but was not inhibited by either immunotoxin. The endothelial cells showed no reactivity with B-B2 and B-B4 and were not inhibited by either immunotoxin. Bone marrow treated with B-B2 and B-B4 immunotoxin did not show a decrease in colonies of hemopoietic precursor cells. Incubation of multiple-myeloma-derived bone marrow with these immunotoxin resulted in a clear decrease of the number of plasma cells. From these data we conclude that B-B2 and B-B4 immunotoxin can be used for ex vivo bone marrow purging. Discrepancies were found between immunohistochemistry, binding assays and cytotoxicity assays with the mAb and the immunotoxin, which underlines the necessity for these various assays as a preclinical screening.

Antibodies, Monoclonal↗
PubMed1996

A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1.

We developed a new monoclonal antibody. B-B4, which specifically identifies human plasma cells. It strongly reacts with all multiple myeloma cell lines and with malignant plasma cells of all tumour samples of the multiple myeloma patients tested. B-B4 does not react with any peripheral blood, bone marrow or tonsil cells. Cloning of the B-B4 antigen reveals that the monoclonal antibody recognizes syndecan-1. It appears that the monoclonal antibody B-B4 is a suitable marker for human plasmocyte identification among haemopoietic cells and a useful probe for the diagnosis of haematological malignancies. Furthermore, this monoclonal antibody can be used for depletions prior to CD34 grafting.

Antibodies, Monoclonal↗
PubMed1996

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1.

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide-exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.

Amino Acid Sequence↗
PubMed1996

Surgical anatomy of the radial nerve in the arm: practical considerations of the branching patterns to the triceps brachii.

Thirty-three cadaveric dissections were performed to identify radial nerve branching patterns to the triceps brachii. Radial innervation of the long head of the triceps originated in the axilla in 88% of the cases and the brachio-axillary angle in 12%. Innervation of the medial head of the triceps originated in the spiral groove in 52% of the cases, the brachio-axillary angle in 39%, and the axilla in 9%. The lateral head was innervated by branches arising in the spiral groove in 70% of the cases, the brachio-axillary angle in 24%, and the axilla in 6%. On average, the radial nerve crossed the midline in the proximal 45% of the arm, 3 cm superior to the level of the deltoid insertion. An intramuscular tendon was present in the medial head of the triceps. The tendon, located medial to the midline of the arm, was seen in all specimens. This tendon serves as an interneural plane with nerve branches descending on either side, but never crossing from one side to the other. Due to the complexity of radial nerve branching, this tendon may be used as a reference plane for longitudinal splitting of the medial head minimizing the risk of nerve damage.

Arm↗
PubMed1995

Comparison of various in vitro assays for efficacy screening of immunotoxins.

Before using immunotoxins in vivo, their efficacy is evaluated in in vitro assays. In this study we compare six different assays for the evaluation of immunotoxins: protein and DNA synthesis inhibition assay, chromium release assay, cell line colony assay, limiting dilution assay and clonogenic assay. All assays except the chromium release assay show specificity of the immunotoxins in appropriate concentrations. The protein and DNA synthesis inhibition assays are easy to perform and, therefore, suitable for initial screening, while the clonogenic assay seems to be the best one for immunotoxin efficacy determination.

Biological Assay↗
PubMed1993

Five-year results of vitrectomy and silicone oil in patients with proliferative vitreoretinopathy.

The purpose for this study was to evaluate the results of silicone oil use in patients who have undergone vitrectomy for proliferative vitreoretinopathy (PVR). The authors reviewed the 5-year results of 50 consecutive patients (52 eyes) with grade C1/D3 PVR operated on in 1987. Silicone oil has been removed in 42 eyes. The retina remained attached in 38 eyes. Visual acuities were finger counting in 12 eyes and 0.1 or greater in 19 eyes. Glaucoma was thought to be the major cause of loss of visual acuity after an initial improvement (9 eyes), as well as the most frequent complication of surgery (13 eyes). Silicone oil was deemed nonremovable in 10 operated eyes. A questionnaire was developed to determine the patients' perceptions of the use of silicone oil, and 46 patients responded to the questionnaire. Four patients indicated that they would not have elected to have surgery again. Six patients thought that surgery was not worthwhile, but would permit treatment again. Most patients thought that a modest amount of improvement had taken place and that vision was stable. Subjectively, most patients believed that surgery was worthwhile.

Evaluation Studies as Topic↗
PubMed1993

Parental divorce and the change in drinking behavior from high school to college.

192 men and 289 women (college students) provided information about their drinking behavior both currently and in their senior year in high school. These data were analyzed by students' sex and family structure. Currently men drank significantly more than women. No differences for family structure were noted. Students from divorced families drank less currently, while students from intact families drank more currently than they did as seniors in high school. This was true for more men than women. Results support the position that current drinking behavior may be associated with a decrease in parental or adult supervision which is experienced earlier for those whose parents have divorced and later (upon entering college) for those students whose parents have not divorced.

Adolescent↗
PubMed1993

[Reimbursement claims of severely handicapped patients in accordance with paragraph 53ff. SGBV--evaluation of social court verdicts].

Sickness insurance bodies pay in case of necessity of nursing the seriously handicapped without having legally defined this term. The medical advisor of the sickness insurance (MDK) examines the necessity of nursing seriously handicapped persons. The article analyses existing social court judgements particularly concerning their consequences on the method of the medical adviser's assessment. The medical expert has to investigate those medical and social facts that are relevant for the administrative and judicial decisions and can appey the regulations of the major associations of the sickness insurances in case of necessity of nursing seriously handicapped persons. The adoption of not properly defined legal concepts from other sections of social legislation is discussed.

Cost Control↗
PubMed1992

Suppression of lymphocyte proliferation by a retroviral p15E-derived hexapeptide.

CKS-17 (LQNRRGLDLLFLKEGGL), a synthetic peptide derived from a conserved region of retroviral transmembrane proteins, has previously been shown to suppress several different immune effector mechanisms. The present study was undertaken to further delineate immunosuppressive site(s) of CKS-17. Overlapping hexapeptides covering the complete sequence of CKS-17 were synthesized. One CKS-17-derived hexapeptide, LDLLFL, suppressed ligand [CD3, interleukin (IL)-2]-induced lymphocyte proliferation. Spontaneous proliferation of transformed lymphoid cell lines, as well as cell lines from myeloid or epitheloid origin, was not inhibited by LDLLFL. Full suppression required the continuous presence of LDLLFL during culturing, and did not involve interference with monocyte function. Radiolabeling studies showed that the hexapeptide did not compete with IL-2 for IL-2 receptor binding. Most likely the LDLLFL motif interferes with steps shared by the IL-2 and CD3 receptor-induced signaling pathways. Since LDLLFL displays multiple immunosuppressive activities, it may constitute a biologically relevant immunosuppressive site of retroviral transmembrane proteins.

Animals↗
PubMed1992

Synthetic hexapeptides derived from the transmembrane envelope proteins of retroviruses suppress N-formylpeptide-induced monocyte polarization.

Retroviral infections are frequently associated with immunosuppression. Retroviral transmembrane envelope proteins (TM proteins) play an important role in this phenomenon. CKS-17, a synthetic heptadecapeptide, represents the immunosuppressive site of these retroviral TM proteins. Here we support on the further delineation of this immunosuppressive site using CKS-17-derived hexapeptides. The N-formyl-methionyl-leucyl-phenylalanine-induced monocyte polarization assay was used throughout this study because this monocyte function has been shown to be highly sensitive to TM protein p15E-related immunosuppression. We found that in addition to CKS-17 one CKS-17-derived hexapeptide, LDLLFL, reversibly inhibited monocyte polarization, with 50% inhibitory concentrations of 20 and 2 microM respectively. LDLLFL-mediated inhibition was sequence specific because the reverse peptide LFLLDL and scrambled peptides were not inhibitory. Hexapeptides corresponding to LDLLFL, but derived from various retroviruses other than murine leukemia virus, also inhibited monocyte polarization. Peptides most homologous to LDLLFL-LDILFL (feline leukemia virus) and LDLLFW (human T lymphotropic virus types I and II)--were the most potent inhibitors. Peptides homologous to primate and human endogenous proviruses were not suppressive. LDLLFL and some of its homologous also inhibited polarization of neutrophilic granulocytes. These findings lend further support to the view that conserved retroviral TM protein-related peptides can play an important role in suppression of inflammatory cell function as encountered in retrovirus-associated immunosuppression.

Adult↗
PubMed1985

Immunoglobulin allotypes are not involved in systemic amyloidosis.

To evaluate the role of immunoglobulin (Ig) allotypes in the pathogenesis of amyloidosis, 8 Gm allotypes and the Km 1 allotype were determined in the sera of patients with amyloid AL (n = 27) and amyloid AA (n = 43). As controls we selected normal individuals (n = 204), 2 patients groups with multiple myeloma (both n = 40) and patients with rheumatoid arthritis (n = 71) and Crohn's disease (n = 47). Our results clearly show that Ig allotypes are not involved in the development of amyloidosis. Our results indicate that the Km 1 allotypic marker is associated with RA.

Amyloid↗