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Biomedical subjects

S Kon

Publications and source records attributed to S Kon.

At least 91 records · Page 5Linked to original sources

Epidermal plasminogen activator inhibitor (PAI) is immunologically identical to placental-type PAI-2.

Plasminogen activator inhibitor (PAI) purified from human epidermis [(1986) FEBS Lett. 408, 273-277] was immunologically identified as placental-type PAI-2. In both fibrinolytic and synthetic substrate assays inhibitory activity of epidermal PAI was neutralized by anti-PAI-2, but not by anti-endothelial type PAI-1. Immunoblotting technique confirmed that the purified epidermal PAI is reactive with anti-PAI-2, but not with anti-PAI-1. Consequently PAI in human epidermis was demonstrable by immunohistochemical technique.

Antibodies, Monoclonal↗

Partial purification of plasma and tissue kallikreins in psoriatic epidermis.

Human psoriatic scale extracts produced kinins from heated plasma (11.3 +/- 5.5 ng kinin/mg protein) and from purified low molecular weight (LMW) bovine kininogen (4.4 +/- 1.7 ng/mg). Sephacryl S-200 gel filtration of the extracts showed three peaks of kininogenase activity with Mr values of 90,000 (K-I), 65,000 (K-II), and 35,000 (K-III). Upon DEAE-Sepharose chromatography of the Sephacryl peaks, K-I activity was found in the nonadsorbed fraction and formed kinins only from heated plasma. Peak K-II activity was resolved into two peaks, K-IIa (in the nonadsorbed fraction), which formed kinins only from heated plasma, and K-IIb (in the adsorbed fraction), which formed kinins from both heated plasma and LMW bovine kininogen. K-III kininogenase activity appeared at the same position as K-IIb and also formed kinins from both substrates. Kininogenases K-I and K-IIa had the same Km value (0.3 mM) with Pro-Phe-Arg-p-nitroanilide(pNA), similar to that found with human plasma kallikrein. The Km value of K-IIb with Val-Leu-Arg-pNA (0.8 mM) was like that found for human salivary kallikrein, whereas K-III had a low affinity for this substrate. Like plasma kallikrein, K-I and K-IIa were inhibited by soybean trypsin inhibitor, but only weakly by aprotinin. In addition the kininogenase activity of both K-I and K-IIa was neutralized by adding antihuman prekallikrein immunoglobulin G (IgG). In contrast, K-IIb and K-III were strongly inhibited by aprotinin but not by soybean trypsin inhibitor, consistent with their being tissue kallikreins. It was confirmed that K-IIb and K-III shares antigenic determinant of urinary kallikrein.

Adolescent↗

[Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody].

It has been over 15 years since Eisen first suggested that immunoglobulin idiotype could serve as a tumor-specific antigen. Over 10 years ago, Stevenson pointed out that B cell malignancies would be ideal targets for the idiotype-directed immune responses because these tumors retain the idiotype molecule on their cell surface rather than secreting it. Since that time a number of studies with animal models have shown that either passive or active immune manipulation directed at cell surface idiotypic determinants could have therapeutic effects on B cell malignancies. In this paper we will summarize and update the results of our clinical trials with anti-idiotype antibodies in patients with B cell malignancies. The results indicate that anti-idiotype antibodies can have profound effects on tumors, causing regressions in the majority of the patients treated. In addition, these studies have revealed that human B cell tumors are idiotypically heterogeneous due to extensive V-region somatic mutation.

Antibodies, Monoclonal↗

The laterally positioned flap.

The laterally positioned flap has shown itself to be the most predictable and esthetically successful procedure in the treatment of mucogingival defects such as gingival/periodontal recessions and root exposures. It is of utmost importance that the biologic principles of wound healing, which have been discussed in the literature and this article, should be adhered to prior to, during, and after the surgical procedure.

Animals↗

Idiotype vaccination against murine B cell lymphoma. Humoral and cellular responses elicited by tumor-derived immunoglobulin M and its molecular subunits.

C3H/HeN mice were immunized with idiotypic immunoglobulin M (IgM) and its molecular subunits from the syngeneic 38C13 lymphoma. Immunization with idiotypic IgM (38C-Id) resulted in idiotype-specific humoral and cellular immunity and protection against a lethal tumor cell challenge. Heavy (H38C) and light (L38C) chains were isolated by electroelution from preparative polyacrylamide gels. Both of these immunogens induced significant resistance to a subsequent tumor challenge. Variable region immunogens, in the form of trpE-fusion proteins, were obtained by cloning heavy and light chain variable region genes into the expression plasmid pATH-11. Of these, only the trpE-VH38C immunogen yielded immune resistance to tumor challenge. Finally, the nucleic acid sequence of 38C-Id light chain was determined and, based on the corresponding amino acid sequence and an analysis of predicted secondary structure, a region of potential antigenicity in complementarity-determining region 3 was chosen for the production of a synthetic peptide. Vaccination with this synthetic peptide resulted in significant suppression of tumor growth. Analysis of the humoral and cellular immunity generated by these vaccines revealed the presence of antibodies reactive with native idiotypic IgM only in 38C-Id, H38C, and trpE-VH38C immune sera, although the latter two were not idiotype-specific. Idiotype-specific lymphocytes, which proliferated in response to native 38C-Id, were observed in all immune animals. With the exception of the fusion protein immunogens, conjugation to an immunogenic carrier protein (keyhole limpet hemocyanin or thyroglobulin) was required for optimal humoral and cellular responses.

Amino Acid Sequence↗

A rapid method for cloning and sequencing variable-region genes of expressed immunoglobulins.

A rapid procedure is described for cloning immunoglobulin V region genes from cells that express them. cDNA is synthesized from mRNA template using primers homologous to the immunoglobulin constant-region genes. Blunt-ended, double-stranded cDNA is obtained by sequential addition of enzymes to a single tube. The cDNA is inserted directly into the M13 vector, which is screened by plaque lifting for the presence of specific inserts. Screening probes can be generated from 32P-labeled single-stranded cDNAs generated from primers different from those used for cloning, or alternatively, from previously cloned V or C gene segments. The ease of cloning a cDNA V region is directly related to the abundance of Ig-specific mRNA within the cell of interest. This method minimizes the number of steps and the time needed to obtain accurate and complete sequences of any expressed Ig V region gene.

Amino Acid Sequence↗

Retention of an idiotypic determinant in a human B-cell lymphoma undergoing immunoglobulin variable-region mutation.

Tumor cells from a patient with B-cell lymphoma were fused with a mouse myeloma cell line. A set of heterohybridomas was thus derived, each of which represented a separate clonal derivative from the tumor cell population. The immunoglobulins secreted by these cell lines reacted variably with a panel of anti-idiotypic antibodies, indicating that the tumor was heterogeneous; however, one antibody, 4D6, reacted strongly with the product of all the heterohybridomas. cDNA for the immunoglobulin heavy chain variable-region genes expressed in these heterohybridomas was cloned and sequenced. Comparison of these sequences indicated that the cells expressing them were clonally related but that they had undergone considerable mutation. Despite mutation, the cells in this tumor population continued to express a functional immunoglobulin molecule and to retain, over a span of 3 years, the idiotypic determinant defined by the 4D6 monoclonal antibody. Thus a selective force existed within the host to retain tumor cells bearing an immunoglobulin molecule with a particular idiotypic structure.

Animals↗

Effects of citric acid and fibronectin and laminin application in treating periodontitis.

To determine the effect on new connective tissue attachment of citric acid conditioning and fibronectin-laminin application in treating naturally occurring periodontitis, all 4 quadrants in each of 2 Beagle dogs were used. Each quadrant included: P2, P3, P4, and M1 teeth. 2 treatment modalities were employed and comparatively analyzed for differences in histological healing respponses at 120 days after surgery. The treatments were: (1) surgery (mucoperiosteal flaps) plus citric acid; (2) surgery plus citric acid followed by fibronectin-laminin application. After scaling and root planing, coronal and root surface reference notches were placed for histometric measurements. Following each of the randomly assigned treatments, flaps were sutured. After sacrifice, tissue blocks of treated areas were decalcified and serially cut, obtaining bucco-lingual and mesiodistal sections. Using a Filar micrometer, 5 distances were masured on the buccal aspect: (1) from root surface notch to alveolar bone crest; (2) from root surface notch to coronal extent of the cementum; (3) from root surface notch to apical extent of the junctional epithelium; 84) from free gingival margin to apical extent of junctional epithelium; (5) from the coronal notch to the alveolar bone crest. Results showed no differences among the 5 measurements between the 2 treatments tested. On mesio-distal sections, surface area determinations were made in the furcations, evaluating the space occupied by new connective tissue, with or without bone, or by epithelium. For this, images were digitized using a Zeiss IBAS Image analysis system with a 4mB of array processor memory coupled to a Newvicon TV camera and a microcomputer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Periodontal probing.

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Epithelial Attachment↗

The effect of citric acid and fibronectin application on healing following surgical treatment of naturally occurring periodontal disease in beagle dogs.

It has recently been suggested that following the exposure of root surface collagen with citric acid, the addition of topically applied fibronectin might promote healing with a fibrous re-attachment. The purpose of this study was to determine the benefit of citric acid demineralization and fibronectin application in the surgical treatment of severe, naturally occurring periodontal disease in Beagle dogs. The 4 treatment modalities employed were: (1) surgery alone (mucoperiosteal flaps); (2) surgery plus fibronectin; (3) surgery plus citric acid; (4) surgery plus citric acid followed by fibronectin application. Coronal and root surface notches were used as biometric and histometric reference points. Final clinical measurements were recorded 6 weeks post surgically, on the day of sacrifice. Significantly increased amounts of connective tissue reattachment were observed in the areas treated with the citric acid/fibronectin combination. Fibrous re-attachment was enhanced at the expense of epithelial downgrowth and occurred directly to both new and old cementum and exposed dentin, often in a functional manner, i.e., perpendicular to the root surface. Areas treated with the surgery and citric acid technique attained moderate amounts of fibrous re-attachment while the other treatment modalities were associated with a long junctional epithelium. The enhanced fibrous re-attachment may be the product of an accelerated coalescing of exposed soft tissue and root surface collagen fibrils, while under the mediating effect of fibronectin.

Animals↗