PubMed Health⌕ Search

Biomedical subjects

J Pound

Publications and source records attributed to J Pound.

13 recordsLinked to original sources
PubMed2003

Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease.

Current therapies for Burkitt's lymphoma (BL) utilise combined cytotoxic chemotherapy, but these treatments are not always available in areas where the disease is endemic and are also markedly less successful in AIDS-related BL. Therefore, additional therapies are urgently required. We demonstrate here that combined fibrates and MPA exert powerful, antiproliferative actions against well-characterised Daudi, Raji and L3055 BL cell lines and primary BL cells. Detailed studies in L3055 demonstrated that this activity was mediated by induced apoptosis and confirmed by observations that overexpression of the antiapoptotic genes bcl-2 or bcl-x(L) conferred significant protection against the drugs. Importantly, since fibrates and MPA are inexpensive and stable with minimal-associated toxicities, we suggest that these drugs should be considered as adjuncts to currently available treatments for BL in endemic and AIDS-related disease.

Antineoplastic Agents, Hormonal↗
PubMed2001

Effect of challenge temperature and solute type on heat tolerance of Salmonella serovars at low water activity.

Salmonella spp. are reported to have an increased heat tolerance at low water activity (a(w); measured by relative vapor pressure [rvp]), achieved either by drying or by incorporating solutes. Much of the published data, however, cover only a narrow treatment range and have been analyzed by assuming first-order death kinetics. In this study, the death of Salmonella enterica serovar Typhimurium DT104 when exposed to 54 combinations of temperature (55 to 80 degrees C) and a(w) (rvp 0.65 to 0.90, reduced using glucose-fructose) was investigated. The Weibull model (LogS = -bt(n)) was used to describe microbial inactivation, and surface response models were developed to predict death rates for serovar Typhimurium at all points within the design surface. The models were evaluated with data generated by using six different Salmonella strains in place of serovar Typhimurium DT104 strain 30, two different solutes in place of glucose-fructose to reduce a(w), or six low-a(w) foods artificially contaminated with Salmonella in place of the sugar broths. The data demonstrate that, at temperatures of > or =70 degrees C, Salmonella cells at low a(w) were more heat tolerant than those at a higher a(w) but below 65 degrees C the reverse was true. The same patterns were generated when sucrose (rvp 0.80 compared with 0.90) or NaCl (0.75 compared with 0.90) was used to reduce a(w), but the extent of the protection afforded varied with solute type. The predictions of thermal death rates in the low-a(w) foods were usually fail-safe, but the few exceptions highlight the importance of validating models with specific foods that may have additional factors affecting survival.

Culture Media↗
PubMed1994

Central role of CD40 and its ligand in B lymphocyte responses to T-dependent antigens.

In order to mount an effective antibody response to soluble and certain other types of antigens, B cells need help from T cells. Recently, an important receptor-ligand pair has been identified as essential for successful cognate interaction between these two classes of lymphocytes. CD40 was first identified as a receptor-like molecule on B cells which when ligated by antibody could deliver signals to prime for growth, differentiation, or survival. Later its counterstructure--termed CD40 ligand (CD40L)--was discovered to be an inducible type II glycoprotein of helper T cells. In this review, the central role of the CD40-CD40L interaction in the various phases of the B cell response to T-dependent antigens is discussed drawing from both in vitro and in vivo studies.

Animals↗
PubMed1994

Effector mechanisms activated by human IgG subclass antibodies: clinical and molecular aspects. Review article.

Secondary systemic immune responses are predominantly of the IgG class and passive administration of intravenous IgG, from pooled normal serum, is an effective prophylactic and/or therapeutic treatment for patients with defined immunodeficiencies. However, the proportions of each IgG subclass present within a specific antibody response may differ dramatically from that of the total IgG pool. For some antigens the response may be essentially restricted to a single subclass and it may be presumed that the antibody isotype produced has an optimal protective role. The clinical consequences of selective IgG subclass deficiency appears to validate this presumption. In this review we emphasize the differences in effector functions activated by the IgG subclasses and hence the mechanisms responsible for the removal and destruction of antigen/antibody complexes. These studies are relevant to diagnosis and treatment of patients with recurrent infection; the IgG isotype of monoclonal antibodies selected for passive in vivo therapy; the generation of customized antibodies having a pre-determined profile of effector functions and 'immuno-direction' with new vaccines to provoke an antibody response having an isotype profile optimal for the proposed application.

Complement Activation↗
PubMed1990

Molecular definition of interaction sites on human IgG for Fc receptors (huFc gamma R).

Evidence from several experimental approaches allows us to conclude that the primary amino acid sequence of the lower hinge region (residues 234-237) of human IgG molecules determines recognition by human Fc gamma RI, Fc gamma RII and Fc gamma RIII. Glycosylation of the CH2 domain is also essential, although the carbohydrate is not accessible for direct interaction with ligands. The role of the carbohydrate moiety may be to maintain a protein conformation that allows accessibility to amino acid side chains essential for ligand recognition and binding. It appears logical that the evolutionarily-related Fc gamma R molecules should interact with overlapping non-identical sites on the IgG molecule.

Amino Acids↗
PubMed1990

Drug regulation--the Canadian approach.

The legislative authority and framework for the regulatory control of drugs in Canada is outlined. The layered approach of the regulatory system is described, including the premarket review mechanism, postmarketing monitoring, and other requirements for specific drug categories. Changes in the Canadian regulatory approach to provide timely and effective drug evaluation are discussed, particularly increased international collaboration, regulatory accommodation for AIDS drugs, rationalized policies for traditional medicines, and the concept of risk/benefit analysis.

Canada↗
PubMedDate not supplied

Relationship of child sexual abuse to depression.

Thirty-nine girls aged 6 to 12 participated in this study, each having been referred for evaluation of suspected child sexual abuse. The study investigated the prevalence of depression in the sample as well as the relationship of depressive symptoms to severity of abuse and potential mediator variables. The Child Behaviour Checklist and Child Depression Inventory were used to asses the severity of depression. A composite score for severity of abuse was derived from child disclosure and medical findings. Results indicated that 67% of the children could be classified as experiencing symptoms consistent with a diagnosis of depression. Severity of abuse was not significantly correlated with depression intensity scores. Stepwise regression analyses revealed that a high number of stressful life events and low IQ were significant predictors of depression scores. The clinical implications of these findings are discussed.

Child↗
PubMedDate not supplied

Beyond takeovers: politics comes to corporate control.

In the 1990s, politics will replace takeovers as the defining tool for corporate governance challenges, and a marketplace of ideas will replace the frenzied activity that once dominated the financial marketplace in the 1980s. In the transaction-driven market of the past, corporate raiders used junk bonds and other financial tools to take control of their targets. In the new marketplace of ideas, debate will replace debt as active shareholders press specific operating policies for their target corporations in a new politicized market for corporate control. John Pound, associate professor of public policy at the John F. Kennedy School of Government at Harvard, reports that investors are already using shadow management committees, independent director slates, and outside experts to influence management policy. Pound cites Carl Icahn's battle for control of USX as an example of the emerging trend. What began as a hostile takeover ended with a negotiated solution in which many constituencies ultimately played a role in the restructuring of the company. This political approach to governance gives management a chance to embrace a bargain that is in its long-term interest. By promoting politically based tactics, managers can generate political capital with their major investors. Managers in companies as diverse as Avon and Lockheed now meet regularly with investors, seeking their input on both financial and strategic decisions. In the new politicized market for corporate control, striking a bargain with long-term investors is ultimately in the best interest of the corporation.

Decision Making, Organizational↗