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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

357 records · Page 20Linked to original sources
PubMedDate not supplied

Nucleophilic proteolytic antibodies.

Proteolytic antibodies appear to utilize catalytic mechanisms akin to nonantibody serine proteases, assessed from mutagenesis and protease-inhibitor studies. The catalytic efficiency derives substantially from the ability to recognize the ground state with high affinity. Because the proteolytic activity is germline-encoded, catalysts with specificity for virtually any target polypeptide could potentially be developed by applying appropriate immunogens and selection strategies. Analysis of transition-state stabilizing interactions suggests that chemical reactivity of active-site serine residues is an important contributor to catalysis. A prototype antigen analog capable of reacting covalently with nucleophilic serine residues permitted enrichment of the catalysts from a phage-displayed lupus light-chain library. Further mechanistic developments in understanding proteolytic antibodies may lead to the isolation of catalysts suitable for passive immunotherapy of major diseases, and elicitation of catalytic immunity as a component of prophylactic vaccination.

Animals↗
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Inhibition and labeling of enzymes and abzymes by phosphonate diesters.

Reactive phosphonate diesters were designed and prepared as inhibitors of serine proteases and esterases. Inactivation of trypsin, chymotrypsin, and butyrylcholinesterase was determined by residual enzymatic activity as well as by the release of a chromogenic or fluorogenic product of the inhibition reaction. Second-order rate constants were determined from rates of nitrophenol formation. Application of the reaction for active-site titration of enzyme preparations is demonstrated. A basic functional group present in the nitrophenyl tropane phosphonate diester was shown to confer selectivity for inactivation of trypsin and chymotrypsin. Biotinylated derivatives of the phosphonate diesters were prepared to permit analysis of proteins modified in the inhibition reaction. Labeled polypeptides were resolved by SDS-PAGE, electroblotted, and detected by streptavidin-peroxidase staining. A detection limit of less than 4 ng, corresponding to 20 nM of trypsin, was demonstrated. Pretreatment of enzymes with DFP or nonbiotinylated phosphonates specifically blocks the labeling. This technique permits identification of serine proteases in complex mixtures with good sensitivity and specificity.

Animals↗
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Natural catalytic immunity is not restricted to autoantigenic substrates: identification of a human immunodeficiency virus gp 120-cleaving antibody light chain.

The autoimmune repertoire is well known from previous studies to be capable of producing catalytic antibodies directed to self-antigens. In the present study, we explored the ability of 26 monoclonal light chains (L chains) from multiple myeloma patients to cleave radiolabeled gp120, a foreign protein. One L chain with this activity was identified. 125I-gp120 and unlabeled gp120 were cleaved at several sites by the L chain, as shown by SDS-polyacrylamide gel electrophoresis, autoradiography, and immunoblotting, respectively. The apparent dissociation constant of the L chain was 130-145 nM, indicating high-affinity gp120 recognition. 125I-albumin was not cleaved by the L chain, and various proteins and peptides did not inhibit gp120 cleavage by the L chain, suggesting that the activity is not a nonspecific phenomenon. The substrate recognition determinants may be conserved in different HIV-1 strains, because gp120 isolated from strains SF2, MN, and IIIB was found to be cleaved by the L chain. Micromolar concentrations of a synthetic peptide corresponding to residues 23-30 of gp120 inhibited the cleavage of 125I-gp120, suggesting that these residues are components of the epitope recognized by the L chain. The toxic effect of gp120 in neuronal cultures was reduced by about 100-fold by pretreatment of the protein with the L chain. These observations open the possibility of utilizing gp120-cleaving antibodies in the treatment of AIDS.

Animals↗
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[Molecular basis of oncogenesis].

After a quarter century of rapid advances, cancer research has generated a rich and complex body of knowledge, revealing cancer to be a disease involving dynamic changes in the genome. Several lines of evidence indicate that tumorigenesis in humans is a multistep process and that these steps reflect genetic alterations that drive the progressive transformation of normal human cells into highly malignant derivatives. The barriers to development of cancer are embodied in a teleology: cancer cells have defects in regulatory circuits that govern normal cell proliferation and homeostasis. This review concern the description of novel capabilities acquired during tumor development.

Animals↗
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[Tumor-induced immunosuppression].

Tumor immunology is based on two essential concepts: immune surveillance, which implicate the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Furthermore, expression of self-antigens on the tumor surface impose potential barriers to the development of effective immune response. Tumors are able to overcome immune surveillance by changing the polarity of effectors cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells is of importance for clinical applications or immunotherapy in cancer treatment.

Animals↗
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Activation of murine bone-marrow derived macrophages in vitro with Thymosin-alpha-1 to tumoricidal state: a comparative study on normal and tumour-bearing hosts.

The present investigation establishes the ability of Thymosin alpha l (T alpha l) to activate murine bone-marrow derived macrophages (BMDMs) in vitro to tumoricidal state with concomitant release of NO, TNFalpha and IL-1. The T alpha l-induced cytotoxicity and the secretion of soluble lytic factors were both dose- and time dependent. BMDMs cultured from the Dalton's Lymphoma bearing mice (DL-BMDMs) exhibited reduced cytolytic activity towards DL-tumour target cells on activation with T alpha l as compared to the BMDMs obtained from normal mice (N-BMDMs). The DL-BMDMs displayed enhanced TNFalpha and IL-1 release as compared to the N-BMDMs when treated with T alpha l. On the other hand, it is observed that the production of NO and the expression of iNOS was higher in the N-BMDMs as compared to the DL-BMDMs on treatment with T alpha l. Although T alpha l could trigger the tumoricidal functions of BMDMs from normal and DL-tumor bearing hosts, the progressive growth of DL-tumour in ascitic form leads to an alteration in the antitumour response of macrophages. These observations further suggest that a disregulation in the production of inflammatory cytokines like TNF-alpha, IL-1 and the inhibition of NO production in response to DL growth may mutually contribute in explaining the tumour-induced immunosuppression as observed in the DL-bearing mice.

Journal Article↗
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Late post radiation laryngeal chondronecrosis with pharyngooesophageal fibrosis.

Chondroradionecrosis of larynx is a well recognized complication of radiation therapy, which usually occur with in the 1st year. Review of literature shows very few accounts of late radiation induced clinical chondroradionecrosis of the larynx. This condition can mimic a local recurrence and severe and life threatening involvement will require aggressive surgical management as reported in the present case.

Adult↗
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Potential correlates of self-care and symptom distress in homosexual/bisexual men who are HIV seropositive.

Although treatment of HIV infections is possible, anecdotal data and research suggest that infected homosexual and bisexual men are developing sets of HIV-specific self-care behaviors that they believe will maintain their health or delay progressive disease. However, little is known about frequent use of HIV self-care in relationship to symptom distress or other factors commonly assessed by nurses. These deficits limit the ability of healthcare providers to intervene appropriately. Consequently, the following repeated-measures study retrospectively examined correlates of HIV self-care in 162 outpatients who were attending a major healthcare facility in San Francisco, CA. Standard and HIV-specific instruments created for the study were used in data collection. Results suggest that the men increased their use of 35 of 81 HIV self-care behaviors once they became aware of being HIV seropositive (p less than 0.001). Frequent use of HIV self-care behaviors was related to several variables, including previous patterns of self-care (p less than 0.001), and AIDS diagnosis (p less than 0.01), and a locus of control (LOC) indicator (e.g., the statement "What happens to me is beyond my control") (p less than 0.001). Symptom distress also was related to several variables, including selected LOC and quality-of-life (QOL) indicators, mood states, and recent diagnosis of selected AIDS-related diseases (p less than 0.01). Collectively, these results suggest that taking self-care and selected psychosocial histories will allow nurses to identify ambulatory patients with HIV infections who need intensive care.

Adult↗
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Cognitive adaptation to stressful events during pregnancy and postpartum: development and testing of the CASE instrument.

The purpose of this article is to describe the development and testing during pregnancy and postpartum of a new instrument, the Cognitive Adaptation to Stressful Events Scale (CASE). The conceptual framework for the CASE is based on Taylor's theory of cognitive adaptation to threatening events using the dimensions of meaning, mastery, and self-esteem. A convenience sample of 202 primigravida women completed the CASE at six assessment points: 10 to 12, 20 to 22, and 30 to 32 weeks of pregnancy and 1 to 2, 8, and 14 weeks postpartum. Regression analysis conducted with CASE scores at each of the assessment points in relation to psychological symptom distress as measured with the SCL-90R Global Severity Index (GSI) indicated a strong relationship during each time period. Although replication with multiethnic, high-risk pregnancy and clinically depressed groups is needed, the CASE is a promising tool for examining the cognitive adaptation process occurring during pregnancy and postpartum.

Adaptation, Psychological↗
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Scanner technology for data-based decision making.

Scanner systems offer several benefits to nurse executives. Clinical, educational, and administrative data can guide the nurse executive's decisions providing greater control over patient care outcomes. Information from large patient care data sets provides a powerful tool for persuading executives in other departments. Additionally, the nurse executive who can eliminate the need for personnel to conduct time consuming and costly manual data entry, may be able to justify financial support for continued development of the nursing department's information system and technological training for the staff. In this way, scanner technology meets the immediate need for information and serves as an entry to more advanced communications systems.

Electronic Data Processing↗
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Effect of fluoride dentifrices on salivary fluoride levels in children.

Fluoride dentifrices are well accepted for their caries preventive effects. The fluoride concentration in the oral fluids after tooth brushing with fluoride dentifrices may have an important relationship to the caries reducing capacity. The present study was aimed to clinically evaluate the salivary fluoride retention of dentifrices containing low fluoride concentration in 50 children, aged 7-9 years before, during and after the use of fluoride toothpaste. Estimation of fluoride in saliva was done using a Orion microprocessor ion analyser with a fluoride specific ion electrode. The results of the present study suggest that there is considerable salivary fluoride retention after brushing with fluoride dentifrices. The retention of fluoride in the saliva at a higher level even with the low fluoride concentration, proves the similar cariostatic effect as of higher concentration.

Child↗