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Biomedical subjects

J E Harris

Publications and source records attributed to J E Harris.

At least 55 records · Page 3Linked to original sources
PubMed1999

Osteopathic family physicians' attitudes, knowledge, and self-reported practices regarding obesity.

The study's purpose was to examine attitudes, knowledge, and self-reported practices of osteopathic family physicians regarding obesity. A survey was developed and administered to osteopathic family physicians. Respondents were predominantly male (76%), and their mean age was 44.6 years. Most had been in practice for fewer than 10 years. Physicians surveyed used diet, exercise, and behavior modification most often in treating obese patients. They were reluctant to suggest medications for treatment of obesity. The physicians also displayed a lack of understanding of the proper assessment of obese patients. These family physicians admitted that medical journals and continuing education were their major sources of information about obesity. Most agreed that their medical school training was deficient in regard to the treatment of obesity, but a majority wished further training. Most of the physicians surveyed had a desire to collaborate on obesity-related research projects. These trends appeared not to be related to physician gender, age, years in practice, or weight. The results of this survey indicated that osteopathic family physicians desire to be updated on current research regarding obesity and use of interdisciplinary modalities. Additional access to training could make an impact on these attitudes and thereby influence their patient management.

Adult↗
PubMed1998

5-Lipoxygenase inhibitors reduce PC-3 cell proliferation and initiate nonnecrotic cell death.

BACKGROUND: Products of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase, stimulate the growth of several cell types. Selective inhibitors of the enzyme, including SC41661A and MK886, reduce PC-3 prostate cell proliferation. With continued culture, cells die, but the mode of death, necrotic or nonnecrotic, has not been established. METHODS: Flow cytometry, laddering after agarose electrophoresis of DNA from inhibitor-treated cells, and light and electron microscopy were employed to examine the type of death in PC-3 prostate cells cultured with either 5-lipoxygenase inhibitor. RESULTS: The inhibitors induced nonnecrotic, programmed cell death. SC41661A-treated cells exhibited "foamy," vacuolated cytoplasm and mitochondria with disrupted cristae and limiting membranes, while some cells contained numerous polysomes and extended hypertrophic Golgi and secretory cisternal networks. A proportion of the treated cells detached and the nuclei of these cells were characteristic of type 1 "apoptotic" programmed cell death. MK886, a 5-lipoxygenase-inhibitor with a different mechanism of action, induced nonnecrotic changes largely confined to the cytoplasm, most consistent with type 2 "autophagic" programmed cell death. In preliminary studies of mechanism, we demonstrated that PC-3 cells express mRNA for 5-lipoxygenase and for 5-lipoxygenase-activating protein. The less active inhibitor, SC45662 neither reduced proliferation nor induced DNA laddering. The antioxidant, N-acetyl-l-cysteine but not butylated hydroxy toluene or alpha tocopherol, partially reduced the inhibition of proliferation from SC41661A. CONCLUSIONS: SC41661A and MK886 inhibit PC-3 cell proliferation and induce a form of type 1 or type 2 programmed cell death, respectively. PC-3 cells contain messenger RNA for 5-lipoxygenase and 5-lipoxygenase-activating proteins. Drug-induced changes included altered redox potential, inferred from the increased survival due to the antioxidant and glutathione precursor, N-acetyl-l-cysteine. PC-3 cells are an appropriate model for studying the mechanism responsible for 5-lipoxygenase inhibitor-induced cellular suicide.

Amides↗
PubMed1998

Inhibition of cancer cell proliferation by disruption of interdigitated/concatenated hierarchies of metabolic control/implementation processes: a proposal.

With a combination of inhibitors at less than their individual 'therapeutic' concentrations directed against dissimilar cellular hierarchical developmental controls and 'downstream' metabolic pathways, it may be possible to modulate the biologic behavior of malignantly transformed cells synergistically. Ideally the cumulative systemic toxicity of such a 'polytherapy' would be reduced.

Cell Division↗
PubMed1998

Phase II study of mitoguazone, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with diffuse histologic subtypes of non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Study (PE481).

Mitoguazone, an investigational agent with significant activity in advanced lymphoma, was added to a modified CHOP regimen (COPA) in an effort to improve the activity of standard therapy in 66 previously untreated patients with stages II-IV lymphoma and diffuse histology of intermediate or high grade other than lymphoblastic in this phase II pilot study. The regimen was well tolerated and the complete response rate in diffuse large cell lymphoma was 55%. Sixty-five percent of all complete responders were in complete response for at least one year. Despite these excellent results. it is unlikely that the addition of mitoguazone improved results compared with those obtained with standard therapy alone, since similar results have been frequently reported with the latter.

Adult↗
PubMed1997

Primary structure and tissue distribution of two novel proline-rich gamma-carboxyglutamic acid proteins.

Two human cDNAs that encode novel vitamin K-dependent proteins have been cloned and sequenced. The predicted amino acid sequences suggest that both are single-pass transmembrane proteins with amino-terminal gamma-carboxyglutamic acid-containing domains preceded by the typical propeptide sequences required for posttranslational gamma-carboxylation of glutamic acid residues. The polypeptides, with deduced molecular masses of 23 and 17 kDa, are proline-rich within their putative cytoplasmic domains and contain several copies of the sequences PPXY and PXXP, motifs found in a variety of signaling and cytoskeletal proteins. Accordingly, these two proteins have been called proline-rich Gla proteins (PRGP1 and PRGP2). Unlike the gamma-carboxyglutamic acid domain-containing proteins of the blood coagulation cascade, the two PRGPs are expressed in a variety of extrahepatic tissues, with PRGP1 and PRGP2 most abundantly expressed in the spinal cord and thyroid, respectively, among those tissues tested. Thus, these observations suggest a novel physiological role for these two new members of the vitamin K-dependent family of proteins.

1-Carboxyglutamic Acid↗
PubMed1997

Augmentation of impaired tumoricidal function in alveolar macrophages from lung cancer patients by cocultivation with allogeneic, but not autologous lymphocytes.

It has been reported that the in vitro development of tumoricidal function in alveolar macrophages from lung cancer patients is reduced significantly when compared to that in peripheral blood monocytes from the same patients or alveolar macrophages from control patients. In the present investigation, a method for potentiating the development of tumoricidal function in alveolar macrophages from lung cancer patients is described. This method, which relies on priming the macrophages with purified, allogeneic peripheral blood lymphocytes from normal donors, could not be demonstrated when autologous lymphocytes from lung cancer patients were used in the priming coculture. The augmentation of tumoricidal function appears to be mediated by one or more soluble factors, since supernatants from cocultures of alveolar macrophages and allogeneic peripheral blood lymphocytes could enhance the cytotoxic function of freshly obtained alveolar macrophages. Furthermore, it appears that NK cells are necessary for this effect, since depletion of CD56+/CD57+ cells from allogeneic lymphocytes eliminated their capacity to enhance alveolar macrophage cytotoxic function. The augmentation of cytotoxic function elicited in alveolar macrophages by this method was not associated with changes in the secretion of tumor necrosis factor alpha, or interleukin 1 beta.

CD3 Complex↗
PubMed1997

Modulation of tumoricidal function in alveolar macrophages from lung cancer patients by interleukin-6.

Previous studies have demonstrated that alveolar macrophages from lung cancer patients are impaired in their ability to develop tumoricidal function when stimulated by activators such as interferon gamma + lipopolysaccharide. However, these same macrophages have been shown to develop significant tumoricidal function when precultured with macrophage-depleted allogeneic peripheral blood lymphocytes from normal donors, an effect that was lost by the elimination of natural killer cells from the allogeneic lymphocyte population. In the present study, the effect of each activation condition on the expression of mRNA for interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF alpha) and IL-6 was determined using reverse transcription/polymerase chain reaction. The results show that the non-permissive activation condition is associated with the expression of mRNA for IL-6 while the permissive activation condition is not. Antibodies against IL-6 were subsequently shown to permit the development of tumoricidal function in alveolar macrophages stimulated with interferon gamma + lipopolysaccharide while IL-6 protein was shown to inhibit the stimulatory action of allogeneic lymphocytes on the development of tumoricidal function in the same alveolar macrophages. Neither the permissive (i.e. allogeneic lymphocyte stimulation) nor the non-permissive (i.e. interferon gamma + lipopolysaccharide) activation condition had any effect on the capacity of alveolar macrophages from lung cancer patients to express mRNA for IL-1 alpha, IL-1 beta or TNF alpha. These results show that IL-6 can regulate the ability of alveolar macrophages from lung cancer patients to be stimulated by interferon gamma + lipopolysaccharide to develop significant tumoricidal function. They also show that allogeneic lymphocytes have the capacity to down-regulate IL-6 mRNA synthesis by alveolar macrophages thereby permitting the development and/or expression of macrophage tumoricidal function.

Antibodies↗
PubMed1997

Oral immunization of rainbow trout with antigen microencapsulated in poly(DL-lactide-co-glycolide) microparticles.

The model protein antigen, human gamma globulin (HGG) was microencapsulated in poly(DL-lactide-co-glycolide) microparticles and administered orally to rainbow trout. Oncorhynchus mykiss (Walbaum, 1792). Using a Western blotting technique it was demonstrated that the dynamics of passage through the gut were different for the microencapsulated and soluble antigen. The association of HGG with microparticles increased the retention time of the antigen in the stomach and delayed its entry into the intestinal region. After the delivery of microencapsulated HGG, antigen was detected in gut contents in fragmented form which suggested that some of the antigen was present at the particle surface and therefore susceptible to proteolysis. However, a greater amount of intact antigen was detected in the posterior intestine and in the bloodstream of fish, which were administered with microparticle-associated than soluble antigen, indicating that the antigen was partially protected. Immunization with microencapsulated HGG resulted in the detection of specific antibody in the serum but levels were not significantly greater than after the delivery of soluble antigen. However, specific antibody was detected in the intestinal mucus of fish which were administered with the microencapsulated antigen after boosting with soluble HGG but not in fish which were primed with the soluble antigen.

Administration, Oral↗
PubMed1997

A 5-lipoxygenase inhibitor at micromolar concentration raises intracellular calcium in U937 cells prior to their physiologic cell death.

Micromolar MK886, a selective inhibitor of 5-lipoxygenase at nanomolar concentration, induces physiologic cell death in U937 and chronic myelogenous leukemia blast cells. When U937 cells were challenged with 10 microM MK886, an acute, biphasic and sustained rise in intracellular Ca2+ occurred, as determined with Fura-2. The initial increase was followed by a transient decline and a larger rise due to an influx of external Ca2+. The first increase and part of the subsequent rise also developed in Ca(2+)-free medium, identifying their origin from intracellular stores. The intracellular Ca2+ concentration of U937 cells that remained after culture for 24 or 48 h with 5 or 10 microM MK886 was not reliably altered from the control values of 130 +/- 8.3 nM. Under similar conditions MK886 did not increase cytosol Ca2+ of a human prostate (PC3) cell line examined in suspension. The increase in intracellular Ca2+ in response to MK886 in calcium-containing medium was confirmed with an ACAS laser spectrometer. U937 cytosol pH was measured with the fluorescent probe BCECF, but not persistent acute or chronic change was induced by MK886. The rapid and sustained rise in Ca2+ induced by MK886 is an early event in U937 cells which subsequently undergo physiologic cell death characterized in many by apoptosis.

Amiloride↗
PubMed1997

What brings intentions to mind? An in situ study of prospective memory.

In a naturalistic study, we aimed to uncover the relationship between thinking about and remembering intentions. Electronic badges allowed us to track the activities of subjects within their work environment. Over two weeks, subjects were asked to respond using a button on their badges (1) every two hours (Time task); (2) whenever they were in a particular room (Place task). In addition, whenever they thought about the task, they were asked to indicate this with their badges. Although subjects thought about the Time task more, they forgot to respond more often than in the Place task. In the Time task, there was a marked absence of thoughts about the task following successful remembering. When subjects remembered the Place task, thoughts increased with proximity to the target location. In both tasks, thoughts about intentions occurred more in places such as stairwells than in locations where people tended to settle. On the basis of these findings, possible mechanisms for prospective memory are discussed.

Cues↗
PubMed1997

Hydrosalpinges adversely affect markers of endometrial receptivity.

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.

Adult↗
PubMed1996

Renal medullary carcinoma: clinical and therapeutic aspects of a newly described tumor.

BACKGROUND: Renal medullary carcinoma is a newly described, aggressive kidney tumor. All patients with the disease have been African-American with sickle cell (SC) trait or hemoglobin SC disease. METHODS: Patient information was obtained from individual patient records and from the Department of Defense national data bank, The Defense Enrollment and Eligibility Reporting System. Data were obtained from either personal review of the patient's records or from discussion with the patient's physician. Cytogenetic studies were performed on one patient. RESULTS: Six patients are presented. All had SC trait. Median age was 24.5 years and 1 patient was female. Time from diagnosis to death averaged 3 months (range 1-7 mos). No objective responses were reported to a wide variety of chemo and immunotherapies: cyclophosphamide, doxorubicin, cisplatin; methotrexate, vinblastine, doxorubicin, and cisplatin; single agent interferon; single agent paclitaxel; or single agent vinblastine. Investigational regimens included topotecan, doxorubicin, and filgrastim; alpha-interferon, interleukin-2, and 5-fluorouracil; and single agent paclitaxel. Cytogenetic studies revealed numerous structural, as well as numerical anomalies. Of the cells successfully karyotyped (n=4), 2 contained abnormalities of chromosome 3 and all contained monosomy 11. CONCLUSIONS: Renal medullary carcinoma is an aggressive, chemoresistant tumor. Time from discovery of tumor to patient death is very short and has been altered by a wide variety of chemotherapies and immunotherapies. An unidentified genetic component is likely present.

Adult↗
PubMed1996

Does an inability to eradicate normal stem cells preclude the cure of some cancers?

Presently, identified signal transduction pathways do not alter normal stem-cell survival. With prostate cancer as a model, the argument is advanced that an inability to eradicate normal androgen-dependent prostate stem-cells precludes successful treatment of transformed, androgen-independent and metastatic progeny. While applying this idea to cancers of non-essential organs or to endocrine cancers seems feasible, the inutility of this approach for most other malignancies appears likely, although not certain.

Animals↗
PubMed1996

Luminal and glandular endometrial epithelium express integrins differentially throughout the menstrual cycle: implications for implantation, contraception, and infertility.

PROBLEM: Integrins belong to a family of cell adhesion molecules that are present on virtually all cells. The temporal and spatial expression of these important proteins on the human endometrium suggests that certain integrins may participate in the cascade of molecular events leading to successful implantation. METHODS: Using immunohistochemistry, we studied the expression of 12 different integrins in up to 600 samples of human endometrium throughout the menstrual cycle. Intensity and distribution of staining was determined using the semiquantitative HSCORE, with specific focus on the differences between glandular and luminal expression. RESULTS: We noted that the glandular and luminal epithelium undergo independent alterations in integrin expression throughout the menstrual cycle. Specifically, glandular epithelium express certain integrins only during the window of implantation, while luminal epithelium down-regulate certain integrins during this time. The expression of one integrin (the alpha v beta 3 vitronectin receptor) on both luminal and glandular epithelium coincides with the time of embryo attachment; aberrant expression of this integrin is associated with infertility. CONCLUSION: It appears that the endometrium is a unique tissue with regard to the number of integrins that undergo temporal and spatial changes during the menstrual cycle. These data may offer new directions for the development of a novel contraceptive approach targeted to the endometrium as well as a better understanding of occult causes of infertility in women.

Contraception, Immunologic↗
PubMed1996

American cigarette manufacturers' ability to pay damages: overview and a rough calculation.

The American cigarette industry's ability to pay large damage awards and settlement costs is not limited to its current annual profits of $7.6 billion, or $0.31 per pack. Much larger liability payments could be financed through increased wholesale cigarette prices or higher excise taxes. An increase in the federal cigarette excise tax of 50 cents per pack could yield an estimated $10.8 billion annually in net revenues available for liability costs, while the industry would still retain $5.4 billion, or $0.25 per pack, in pre-tax profits. An increase in cigarette price from its current $1.88 per pack to the full, monopoly profit-maximising level of $4.08 per pack would make more than $32 billion available annually for liability payments or pre-taxed profits.

Humans↗
PubMed1996

Ultrastructural study of the epithelium of the normal human vulva.

An ultrastructural study of the pathology of vulvar vestibulitis syndrome (Friedrich, 1987) necessitated a detailed knowledge of the epithelial surface of the vulva. As this has previously been characterised only at the light microscopy level, a comprehensive electron microscopical study of the vulva was considered critical to the study of the pathological tissue. A comparison between vulvar, vaginal and keratinised perineal epithelia, confirmed the resemblance of vulvar epithelium to partially keratinised mucosal-like epithelia. No conclusive evidence of keratinisation was observed and the characteristic granular and spiny cell layers found in skin were absent. The prominent cell type was the glycogenated intermediate cell, which formed a structurally homogeneous layer of cells. Other cell types present were: superficial flattened cells, many having nuclei, traces of organelles and large glycogen deposits; suprabasal cells; and basal cells, some of which appeared mitotically active rich in organelles. All cell layers were characterised by the presence of numerous interdigitating cytoplasmic processes, small numbers of infrequent desmosomal junctions and pale staining cytokeratin filaments.

Adult↗