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Biomedical subjects

K D Jones

Publications and source records attributed to K D Jones.

At least 37 records · Page 2Linked to original sources

Involvement of interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi's sarcoma herpesvirus-associated infected primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is a distinct type of lymphoma associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. To determine the factors responsible for the unrestrained proliferation of PEL, we have studied the growth factor requirements of the PEL-derived BCBL-1 and BC-1 cell lines. Both cell lines were found to be autocrine growth factor dependent and to release human interleukin-6 (IL-6), viral IL-6 (vIL-6), and human IL-10 in the culture supernatant. To establish whether these cytokines contribute to autocrine growth, neutralizing antibodies against human IL-6, vIL-6, human IL-10, and soluble IL-10 receptor were used. These experiments showed that human IL-10 and, to a lesser degree, vIL-6 serve as autocrine growth factors for BCBL-1 and BC-1 cells. Thus, human IL-10 and vIL-6 are growth factors released and used by PEL cells for autonomous proliferation and may be critical to the development and progression of PEL.

Antibodies, Monoclonal↗

Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth.

Several angiogenesis inhibitors are fragments of larger proteins that are themselves not active as angiogenesis inhibitors. Vasostatin, the N-terminal domain of calreticulin inclusive of amino acids 1-180, is an angiogenesis inhibitor that exerts antitumor effects in vivo. In the present study, we examined whether the full-length calreticulin molecule shares the antiangiogenic and antitumor activities of vasostatin. Similar to vasostatin, calreticulin selectively inhibited endothelial cell proliferation in vitro, but not cells of other lineages, and suppressed angiogenesis in vivo. When inoculated into athymic mice, calreticulin inhibited Burkitt tumor growth comparably with vasostatin. Calreticulin lacking the N-terminal 1-120 amino acids inhibited endothelial cell proliferation in vitro and Burkitt tumor growth in vivo comparably with vasostatin. An internal calreticulin fragment encompassing amino acids 120-180 also inhibited endothelial cell proliferation in vitro and angiogenesis in vivo comparably with calreticulin and vasostatin. These results suggest that the antiangiogenic activities of vasostatin reside in a domain that is accessible from the full-length calreticulin molecule and localize to calreticulin N-terminal amino acids 120-180. Thus, calreticulin and calreticulin fragments are inhibitors of angiogenesis that directly target endothelial cells, inhibit angiogenesis, and suppress tumor growth. This information may be critical in designing targeted inhibitors of pathological angiogenesis that underlies cancer and other diseases.

Angiogenesis Inhibitors↗

Cybernetic model of the growth dynamics of Saccharomyces cerevisiae in batch and continuous cultures.

Growth of Saccharomyces cerevisiae on glucose in aerobic batch culture follows the well-documented diauxic pattern of completely fermenting glucose to ethanol during the first exponential growth phase, followed by an intermediate lag phase and a second exponential growth phase consuming ethanol. In continuous cultures over a range of intermediate dilution rates, the yeast bioreactor exhibits sustained oscillations in all the measured concentrations, such as cell mass, glucose, ethanol, and dissolved oxygen, the amounts of intracellular storage carbohydrates, such as glycogen and trehalose, the fraction of budded cells as well as the culture pH. We present here a structured, unsegregated model for the yeast growth dynamics developed from the 'cybernetic' modeling framework, to simulate the dynamic competition between all the available metabolic pathways. This cybernetic model accurately predicts all the key experimentally observed aspects: (i) in batch cultures, duration of the intermediate lag phase, sequential production and consumption of ethanol, and the dynamics of the gaseous exchange rates of oxygen and carbon dioxide; and (ii) in continuous cultures, the spontaneous generation of oscillations as well as the variations in period and amplitude of oscillations when the dilution rate or agitatin rate are changed.

Models, Biological↗

Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.

An endothelial cell inhibitor was purified from supernatant of an Epstein-Barr virus-immortalized cell line and identified as fragments of calreticulin. The purified recombinant NH2-terminal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. We have named this NH2-terminal domain of calreticulin vasostatin. When inoculated into athymic mice, vasostatin significantly reduced growth of human Burkitt lymphoma and human colon carcinoma. Compared with other inhibitors of angiogenesis, vasostatin is a small, soluble, and stable molecule that is easy to produce and deliver. As an angiogenesis inhibitor that specifically targets proliferating endothelial cells, vasostatin has a unique potential for cancer treatment.

Animals↗

Interpretation of biopsy findings in the transplant liver.

With several thousand liver transplants being performed each year and many patients being managed in their local medical centers, much of the interpretation of transplant liver biopsy specimens has moved from the transplant hospital to the community setting. This article discusses both typical and more peculiar changes that occur in the transplant liver biopsy specimen. Accurate interpretation requires clear knowledge of these possible changes as well as knowledge of clinical data, such as time elapsed since transplantation and the patient's primary disease.

Biopsy↗

Expanding the praxis debate: contributions to clinical inquiry.

Nursing science continues to debate the adequacy of various philosophic paradigms for their ability to forward the discipline. Nursing must embrace multiple paradigms, methodologies, and their philosophic assumptions to adequately address the complex and multifaceted human phenomena that is the focus of clinical inquiry in nursing. This article examines the differences in interpretive and critical approaches to clinical inquiry relative to praxis, expanding how praxis can be used to inform nursing practice. Differences in the nature of knowledge, goals of inquiry, and claims to praxis between the interpretive and critical traditions are discussed. Praxis, realized through clinical inquiry in both the interpretive and the critical paradigms, may contribute important pieces of the puzzle to improve the human condition. Expanding the praxis debate challenges nurses to consider the emancipatory possibilities of clinical inquiry within both interpretive and clinical paradigms.

Clinical Nursing Research↗

Lovastatin induces growth inhibition and apoptosis in human malignant glioma cells.

The competitive HMG-CoA reductase inhibitor lovastatin has been shown to suppress growth and induce morphological changes in a variety of non-glioma tumor cell lines. This study assesses the effects of this agent on the growth and survival of the human malignant glioma cell lines A172 and U87-MG. The response to the drug was investigated using a cell proliferation assay which revealed significant dose-dependent growth inhibition. Treatment with as little as 100 nM lovastatin over a period of 72 hours led to DNA degradation into nucleosome-sized fragments characteristic of apoptosis. Our data suggest that HMG-CoA reductase inhibitors such as lovastatin merit further investigation as potential therapeutic agents for the treatment of malignant gliomas.

Apoptosis↗

Regression of experimental Burkitt's lymphoma induced by Epstein-Barr virus-immortalized human B cells.

Epstein-Barr virus (EBV)-immortalized human B cells survive only transiently when injected subcutaneously into athymic mice, whereas Burkitt's lymphoma cells give rise to progressively growing subcutaneous tumors. In this study, we tested whether these Burkitt's tumors could be induced to regress via a bystander effect induced by EBV-immortalized B cells. Simultaneous inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in the same subcutaneous site resulted in tumors that regressed with necrosis and scarring. Similarly, simultaneous inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in separate subcutaneous sites resulted in regression of a proportion of the Burkitt's tumors. Furthermore, most of the established human Burkitt's tumors regressed with necrosis and scarring after intratumor inoculations with EBV-immortalized B cells. The EBV-immortalized B cells continued to exert this antitumor effect even when killed with irradiation. The experimental approach to Burkitt's lymphoma treatment described here exploits the ability of athymic mice to reject EBV-immortalized B cells to target an effective antitumor response to malignant cells normally incapable of eliciting it.

Animals↗

Vulvodynia: diagnostic techniques and treatment modalities.

Vulvodynia is a chronic vulvar discomfort often characterized by the patient's complaint of burning, stinging, irritation, or rawness. Vulvodynia has been recorded for centuries. Successful diagnostic techniques and treatment modalities, however, have come about only in the last decade. An accurate diagnosis is based on an exhaustive history and detailed physical examination. Highly technical and costly diagnostics provide little supplemental information. Differential diagnosis, previously called subsets of vulvodynia, includes infections (Candida, human papillomavirus, and herpes simplex virus), dermatoses (lichen sclerosus and inflammatory dermatoses), vulvar vestibulitis, iatrogenic causes, and dysesthesias (pudendal neuralgia and reflex sympathetic dystrophy). Primary care providers are fully capable of accurately diagnosing and managing vulvodynia patients, relying on subspecialty referral only for surgical intervention in selected cases.

Adult↗