Biomedical subjects

J J Freeman

Publications and source records attributed to J J Freeman.

At least 19 recordsLinked to original sources

PubMed2005

Spectral reflectance and morphologic correlations in eastern Terra Meridiani, Mars.

The Mars Express Observatoire pour la Minéralogie, l'Eau, les Glaces, et l'Activité (OMEGA) hyperspectral image data covering eastern Terra Meridiani indicate the ubiquitous presence of molecular water in etched terrain materials that disconformably overlie heavily cratered terrains and underlie the hematite-bearing plains explored by the Opportunity rover. Identification of crystalline water in kieserite (MgSO4.H2O) is linked to materials exposed in a valley and plateau to the north of hematite-bearing plains. The mineralogical similarities between the etched terrain deposits examined with OMEGA data and the layered rocks examined by Opportunity imply that the ancient aqueous environments inferred from analyses of the rover data extend over regional scales.

Extraterrestrial Environment↗

PubMed2001

Raman spectroscopic detection of changes in bioapatite in mouse femora as a function of age and in vitro fluoride treatment.

Laser Raman microprobe spectroscopy, which characterizes the molecular structure of a mineral, was used to analyze microscopically small regions of bioapatite in mouse femora in order to study the effect of mouse age and in vitro fluoride treatment on the bone mineral (i.e., mineral identity and degree of crystallinity). Both femora that had and those that had not undergone in vitro NaF treatment underwent point analysis of 1 micron spots in the center of the compact bone's cross-section. The Raman spectra of bones treated with fluoride showed a peak up-shift of the PO4 vibration mode from 961 to 964 delta cm-1 indicating a conversion from a carbonated hydroxylapatitic to a carbonated fluorapatitic mineral phase. The spectral band width of the 961 delta cm-1 PO4 vibration in femora of 4-, 10-, and 24-week-old mice showed that aging, as well as in vitro treatment with 1.5 M NaF for 12 hours, significantly increases the degree of crystallinity of the bioapatite. In vitro fluoridation of 10-week-old mouse femora increased the bioapatite's degree of crystallinity to about the same degree as did aging to 24 weeks. Four-point bending tests indicated that the age-related increase in crystallinity of untreated bones was associated with decreased deformation to failure, i.e., increased brittleness. In contrast, the increased crystallinity following fluoridation of 10-week-old bones was associated with increased deformation, i.e., increased ductility, perhaps due to the altered mineral composition. This study shows that the laser Raman microprobe readily detects the conversion of carbonated hydroxylapatite to carbonated fluorapatite, as well as changes in crystallinity of either mineral phase, in microscopically small regions of a bone sample.

Aging↗

PubMed1999

Assessment of the utility of the micronucleus test for petroleum-derived materials.

The micronucleus test is a commonly used in vivo assay for chromosomal damage and is an integral part of many mutagenicity testing strategies. The present report describes an assessment of the micronucleus test for the detection of mutagenic potential of petroleum-derived materials. To this end, studies were conducted with catalytically cracked clarified oil (CCCO). This material contains high levels of polycyclic aromatic constituents (PAC) and is a very potent inducer of mouse skin tumors. CCCO is also active in the Salmonella assay and other in vitro tests. As CCCO is the most potent of the various petroleum-derived materials in other assays, it was assumed to be the most easily detectable in the micronucleus test. CCCO was tested in standard mouse micronucleus tests utilizing oral and intraperitoneal injection for test material administration. All of these studies were negative, although DMBA, tested at roughly equivalent levels based on potency in the Salmonella assay, produced statistically significant increases in micronucleus frequency. In a second series of studies, aromatic fractions of CCCO were prepared and tested at up to acutely toxic levels. Results of these studies were also negative. Finally, another petroleum-derived material which is carcinogenic and contained PAC was tested in the micronucleus assay. It also produced negative results. Thus, it was concluded that petroleum-derived materials do not produce clastogenic effects in vivo in the mouse micronucleus test, despite the fact that some pure polycyclic aromatic hydrocarbons are quite active in this assay.

Animals↗

PubMed1999

Inhibition of thymopoiesis of CD34+ cell maturation by HIV-1 in an in vitro CD34+ cell and thymic epithelial organ culture model.

The mechanisms by which HIV-1 affects thymopoiesis were determined by preincubating CD34+ cells or cultured thymic epithelial (CTE) cells with lymphotropic (T-) and monotropic (M-) strains of HIV-1 in an in vitro CTE organ and CD34+ cell coculture model that allows for analysis of development of thymocytes and mature T cells. When purified CD34+ cells were precultured with either T- or M-tropic strains of HIV-1, thymopoiesis was impaired in a two-week coculture manifested by decreased cell number of thymocytes generated. However, the percentages of thymocyte subpopulations were comparable to control uninfected cocultures. Furthermore, HIV infection of thymocytes was predominantly observed in the CD44+CD3- population. However, in a four-week coculture experiment, HIV infection and depletion of more mature thymocytes were also observed. When CTE cells were preincubated with T- and M-tropic strains of HIV before addition of CD34+ cells, the number of thymocytes and subpopulations of thymocytes at early and later stages of maturation were markedly decreased. Furthermore, CD34+ and CD44+CD3- cells become HIV-infected. In summary, HIV-1 infection inhibited thymocyte maturation at early stages of thymocyte maturation CD44+CD25-CD3-. In addition, HIV also depleted later stages of CD4+ thymocyte subpopulations.

Antigens, CD34↗

PubMed1999

Thymosin-alpha1 stimulates maturation of CD34+ stem cells into CD3+4+ cells in an in vitro thymic epithelia organ coculture model.

The effect of thymosin-alpha1 on thymopoiesis is largely unknown. Thymosin is found in the cortical and medullary thymic epithelia, as well as in nurse cells; thus, it is hypothesized that thymosin may affect both early and late stage of thymocyte maturation. In this study, the effect of thymosin-alpha1 on thymopoiesis was determined by coculturing in vitro CD34+ stem cells (SC) with allogeneic cultured thymic epithelia fragments (CTEF) for 1-4 weeks and analyzing T-cell maturation by flow cytometry. Thymosin-alpha1 significantly enhanced the cell number (e.g., proliferation) of mononuclear cells obtained at 2 and 4 weeks of the SC-CTEF cocultures (P < 0.01 and < 0.05, respectively). In particular, thymosin-alpha1 stimulated expression of CD3+ cells at 3 and 4 weeks (P < 0.05). The predominant subpopulation increased by thymosin stimulation was single positive mature CD4+ cells, which was confirmed to occur within the SC-CTEF thymic organ tissue by laser confocal immunofluorescence microscopy. Thymosin stimulation tended to enhance IL-7 synthesis, critical cytokine in the maturation of thymocytes. In summary, this is the first study to demonstrate that thymosin-alpha1 enhanced thymopoiesis of CD34+ stem cells in humans using an in vitro model of differentiation using stem cells and cultured thymic epithelial fragments cocultures. Furthermore, the thymosin significantly increased expression of CD3+4+ T cells.

Adjuvants, Immunologic↗

PubMed1999

The role of dermal irritation in the skin tumor promoting activity of petroleum middle distillates.

Petroleum middle distillates (PMDs), a class of hydrocarbons which boil between 350-700 degrees F, are tumor promoters in mouse skin. The promotional activity is produced under conditions that also result in local changes, including chronic irritation and epidermal hyperplasia. The present study was conducted by comparing equal weekly doses of irritating and minimally or nonirritating test materials, to assess whether tumor promotion was a secondary response to these effects. Four PMDs, C10-C14 normal paraffins (NP), lightly refined paraffinic oil (LRPO), Jet Fuel A (JF), and steam-cracked gas oil (SCGO), were evaluated. Test materials were applied undiluted (2x/week) or as 28.6% (7x/week) or 50% (4x/week) concentrations in mineral oil for 52 weeks following initiation with dimethylbenzanthracene (DMBA). When applied undiluted, all materials produced moderate irritation and significant increase in tumor incidence. When NP, LRPO, or JF were applied in mineral oil diluent, skin irritation was generally ameliorated and few, if any, tumors were produced. SCGO was irritating and produced a significant increase in tumor frequency when administered in mineral-oil diluent. These data indicate that the promotional activity of straight-run PMDs is likely related to chronic irritation at the application site and not to dose. Thus, when used appropriately in the absence of prolonged irritation, these materials should not present a tumorigenic hazard to humans.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Analysis of breast implant capsular tissue for crystalline silica and other refractile phases.

This study questions previous reports of the presence of micrometer-sized areas of crystalline silica in pathologic tissue sections that are based exclusively on polarized-light microscopy. By using optical principles, it can be argued that it is impossible to identify unambiguously or to detect the birefringence of crystalline silica in 5-microm-thin sections. To clarify whether silicone, amorphous silica, or crystalline silica occurs in micrometer-sized moieties in standard 5-microm-thick tissue sections, one needs to apply a structural means of analysis in addition to optical microscopy. This study recommends the use of the laser Raman spectroscopic technique, which is very well suited to clarify this highly controversial issue in future pathologic studies.

Breast↗

PubMed1998

Short-term biomarkers of tumor promotion in mouse skin treated with petroleum middle distillates.

Topical application of certain petroleum middle distillates (PMD) to mice produces skin tumors after long latency, and initiation/promotion protocols indicate that this effect is associated with their tumor promoting activity. Since induction of sustained, potentiated epidermal hyperplasia is predictive of promoting activity, five compositionally distinct PMD [hydrodesulfurized kerosene (API 81-07); hydrodesulfurized PMD (API 81-10); odorless light petroleum hydrocarbons; severely hydrotreated light vacuum distillate (LVD); and lightly refined paraffinic oil (LRPO)] were assessed for their effects on epidermal hyperplasia. PMD were administered (2 x/week for 2 weeks) to skin of CD-1 mice. Four quantitative biomarkers of epidermal hyperplasia were evaluated: epidermal thickness, number of nucleated epidermal cells per unit length of basement membrane, labeling (BrdUrd) index of epidermal cells, and induction of epidermal ornithine decarboxylase (ODC) activity. As positive controls, 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-dodecane were utilized. PMD-induced skin irritation was evaluated visually and/or histopathologically. All five PMD produced dose-dependent, skin irritation and epidermal hyperplasia. On a weight basis the magnitude of the maximal PMD-induced effects was similar to that produced by n-dodecane, but > 1000-fold less than that produced by TPA. Epidermal hyperplasia and subacute skin irritancy produced by the five PMD were similar. Of the four short-term markers of tumor promotion assessed, labeling index and epidermal ODC activity were predictive of the relative promoting activities of those PMD for which tumorigenicity bioassay data are available, i.e., API 81-07 > API 81-10 > LRPO. An apparent discrepancy to the predictability of epidermal ODC activity occurred with LRPO:toluene [1:1 (v/v)]. This mixture is nontumorigenic, yet significantly induced epidermal ODC activity. This mixture, however, produced severe epidermal toxicity that precluded any meaningful analysis of short-term biomarkers in relationship to biological activity.

Administration, Topical↗

PubMed1996

Variable responses of species and strains to white mineral oils and paraffin waxes.

Recent dietary studies on mineral hydrocarbon (MHC) white oils and waxes have shown inflammatory effects in Fischer 344 (F-344) rats, but not in other rat strains or dogs. Histopathologic effects seen in F-344 rats include mesenteric lymph node histiocytosis, liver granulomas, and inflammation of the mitral valve (only seen with paraffin waxes). Human ingestion of MHC can result in noninflammatory lipogranulomas (oil droplets) in tissues which are regarded as clinically unimportant. It is speculated that inherent interspecies differences in pharmacokinetics and/or immune function may contribute to the differential response to MHC seen in F-344 rats. The F-344 rat retains greater amounts of MHC in target tissues compared to other rat strains and dogs and appears to be more sensitive immunologically to MHC than other species, including humans. This strain may be predisposed to these effects as indicated by a high background incidence of inflammatory granulomatous lesions in control female F-344 rats. Because of its apparently unique sensitivity, relevance of effects seen in F-344 rat to human health is questionable and requires further investigation.

Animals↗

PubMed1996

Regulatory mechanisms of choline production.

This paper gives a short account of the mechanisms regulating choline production. Although choline is absorbed from the GI tract and biosynthesized in the liver, its subsequent metabolism to choline esters and phospholipids seems to dominate in importance as to its regulatory role in maintaining a constant source of free choline extracellularly.

Animals↗

PubMed1995

Subchronic feeding study of four white mineral oils in dogs and rats.

Subchronic 90-day feeding studies were conducted on four highly refined white mineral oils to determine any potential for toxicity in Long-Evans rats (20 per sex per dose level) and beagle dogs (4 per sex per dose level). Each oil was fed at dietary dose levels of 300 ppm and 1500 ppm (w/w). No treatment-related effects of toxicological importance were detected in daily observations of general health or in periodic assessments of food consumption and body weight, hematology, serum clinical chemistry, and urinalysis. Observations in dogs suggested that the white oils produced mild laxative effects. Gross and histopathologic examinations, as well as measurements of organ weights, did not reveal any macroscopic or microscopic changes which could be due to treatment. In addition, special staining by Oil Red O of liver, mesenteric lymph nodes, spleen, gastrointestinal tract, stomach, and kidneys indicated no evidence of oil or lipid deposition. A special re-examination of tissues from female and male rats, in response to more recent conflicting data from the Fischer 344 strain, found no histopathologic signs of macrophage accumulation and/or microgranuloma formation in liver, spleen, or mesenteric lymph nodes. These data indicate that repeated exposure to relatively high levels of white mineral oils in the diets does not produce significant subchronic toxicity in Long-Evans rats or beagle dogs.

Animals↗

PubMed1994

Evaluation of the genetic toxicity of middle distillate fuels.

Petroleum middle distillate (PMD) fuels are mixtures of hydrocarbons that distill between approximately 170-370 degrees C. Commercial products that fall into this category include kerosine, diesel fuel, jet fuel, and home heating oil. These products contain both saturated (paraffins and cycloparaffins) and aromatic species, but because of the boiling range normally contain very small amounts of the 3-6 ring polycyclic aromatic hydrocarbon (PAH) constituents, which are considered to be carcinogenic. Nevertheless, there is evidence of weak tumorigenic activity when these materials are repeatedly applied to mouse skin. In the current studies representative products were tested in two commonly used, short-term assays for genetic toxicity, the Salmonella/mammalian microsome mutagenicity assay and the mouse bone marrow micronucleus test. All samples were inactive in the micronucleus assay, and three were clearly inactive in the Salmonella test. Of the remaining two, one was marginally active in the Salmonella assay, and one was equivocal. The marginally active sample contained detectable levels of PAH due to the use of catalytically cracked materials as blending stocks. The results indicated that PMDs that do not contain cracked material were not mutagenic. Thus they may produce tumors via nongenotoxic processes. Those products that do contain cracked stocks may have sufficient PAH to be mutagenic in the Salmonella assay, and in those cases the PAH might also contribute to tumor formation.

Analysis of Variance↗

PubMed1994

Increased frequency of resistance to terminal differentiation in C3H mouse cells produced by genotoxic but not nongenotoxic carcinogens.

Certain cells present in mouse skin are resistant to calcium-induced terminal differentiation. It is believed that these calcium-resistant cells (CRCs) represent an early stage in the carcinogenic process, in part, because frequency increases after treatment with mutagens. The frequency of CRCs in C3H mouse skin was measured before and after treatment with certain petroleum-derived materials. One objective was to determine whether this assay could differentiate between genotoxic and nongenotoxic mouse skin carcinogens. An additional objective was to determine whether CRCs are an important factor in the tumorigenicity of petroleum middle distillates (PMDs), a class of apparently nongenotoxic mateials. Three petroleum-derived materials were tested: mineral oil (MO), a noncarcinogenic product used as the negative control; catalytically cracked clarified oil (CCCO), a highly carcinogenic and mutagenic material; and a lightly paraffinic (LRPO), a PMD which has produced tumors when repeatedly applied, but is not mutagenic and does not initiate most skin tumors. The CRC frequency was not increased by LRPO treatment; however, a statistically significant and dose-related increase was produced by CCCO. These results are consistent with observations that genotoxic, petroleum-derived liquids are capable of tumor initiation in mouse skin, whereas PMDs which are not genotoxic do not initiate skin tumors. The number of CRCs in untreated and MO-treated mice was approximately twice the tumor frequency measured in bioassays of PMDs. Thus, tumor production associated with these products could be due to promotion of preexisting, spontaneously initiated cells.

Animals↗

PubMed1994

Evaluation and management of sialorrhea of pregnancy with concomitant hyperemesis.

This article describes two gravid patients who presented with first-trimester sialorrhea and hyperemesis. Although excessive salivation, especially when accompanied by protracted nausea and vomiting, is an unusual occurrence, it can have serious consequences for both the mother and fetus when left untreated. Initially, phenothiazine was prescribed and later belladonna alkaloid was added separately to the two treatment regimens. In order to successfully treat the excessive salivation, it was necessary to control the nausea and vomiting. Eradication of sialorrhea and hyperemesis were effected 10 days posttreatment. For both patients, pregnancy, delivery, and postpartum intervals proceeded uneventfully. Mothers and infants remain in good health 2 years posttreatment.

Adult↗

PubMed1994

Inappropriate breast secretions of possible bacterial etiology in the parous nonpuerperal female.

This article presents two cases of spontaneous green breast secretions of parous nonpuerperal patients. To understand the nature of these secretions, bacterial evaluations and subsequent treatment were undertaken. Case 1 culture and sensitivity studies from breast secretions were commenced within 24 hours yielding an isolate identified as Staphylococcus epidermidis, with sensitivity to cephalothin, erythromycin, and tetracycline but resistant to penicillin. Cephalothin, 500 mg four times a day for 10 days, followed by erythromycin 100 mg twice a day for 10 days and doxycycline 100 mg twice a day for 10 days, did not alter the breast secretions. Four weeks later, ciprofloxacin HCI 500 mg twice a day for 6 weeks caused a 50% decrement in breast secretion at 4 weeks but increased clinical depression. At 6 weeks, no evidence of breast secretions persisted. Mental depression decreased within 2 weeks postciprofloxacin treatment. In Case 2, a total of 35 minutes elapsed between sample collection and initiation of culture and sensitivity studies. Moraxella osloensis was identified and found sensitive to ampicillin and tetracycline but resistant to trimethoprim. Ampicillin 500 mg four times a day for 10 days and doxycycline 100 mg twice a day by mouth for 10 days were administered at 2-week intervals with no effect on breast discharge. After 4 weeks of treatment failure, ciprofloxacin HCI 500 mg twice a day for 6 weeks caused a 50% decrease in discharge at 2 weeks and total elimination at 6 weeks. Lethargy during treatment ceased with termination of therapy. These results support the importance of bacterial evaluation of breast secretions with subsequent antibiotic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Evaluation of the contribution of chronic skin irritation and selected compositional parameters to the tumorigenicity of petroleum middle distillates in mouse skin.

Two-year skin carcinogenicity studies were conducted in C3H mice to assess the effects of irritation and selected compositional parameters on the carcinogenic potential of four petroleum liquids. Three samples (lightly refined paraffinic oil, LRPO; lightly hydrodesulfurized specialty oil, LHSO; jet fuel, JF) can be generically classified as middle distillates, i.e. distillation occurs between 350 and 700 degrees F (175-370 degrees C). The fourth sample was a Steam Cracked Gas Oil (SCGO) that distilled within the same range. In studies that assess the effects of irritation on tumorigenicity, LRPO was tested undiluted or was diluted to 50% and 25% in either mineral oil (which eliminated irritation of the skin) or toluene (which did not). Undiluted LRPO elicited tumors in 8% of the mice. Both dilution procedures eliminated tumorigenic potential. Thus, it was possible to maintain a visible level of skin irritation equivalent to that elicited by undiluted LRPO without inducing tumors. SCGO elicited a chronic irritant state grossly equivalent to LRPO but was not tumorigenic. Jet Fuel A (JF) was tested undiluted using both a standard skin painting protocol and an intermittent dosing schedule in which treatment was suspended periodically to allow skin irritation to resolve. The standard treatment protocol of JF resulted in both marked skin irritation and tumors in 44% of the mice. However, using the intermittent schedule, the tumor yield was reduced to 2%. Collectively these data demonstrate that tumor formation is not a necessary sequelae to chronic skin irritation. Conversely, prevention of a marked chronic irritant state was accompanied by decreased tumor yield. These data suggest that the chronic irritant state may be a necessary but not sufficient condition for tumor formation. In studies to assess the effects of compositional parameters, a lightly hydrodesulfurized specialty oil (LHSO) similar to LRPO but refined to have negligible levels of sulfur compounds (3 ppm), elicited chronic irritant and tumor responses (10%) similar to LRPO. Thus, the level of sulfur compounds does not appear to affect the tumorigenic activity for products in this boiling range. The SCGO which did not produce tumors contained only aromatic hydrocarbons, a finding consistent with previous reports that aromatics may not be the source of tumorigenic potential in petroleum fractions boiling between 350 and 700 degrees F (175-370 degrees C).

Animals↗

PubMed1992

Preparation, purification, and determination of the biological activities of 12 N terminus-truncated recombinant analogues of bovine placental lactogen.

Removal of 13 to 15 amino acids from the N terminus of bovine placental lactogen (bPL), which according to the three-dimensional structure of pGH corresponds to a nonhelical part of bPL, did not effect its secondary structure or change the monomer content of the protein preparation. However, it remarkably decreased the binding of the prolactin (PRL) type of receptors on Nb2 cells with subsequent reduction in bioactivity. The binding to the growth hormone (somatogen) receptors either did not change or was increased, resulting in an increase of somatogen receptor-mediated bioactivity. Further truncation (17-18 amino acids) resulted in a decrease of alpha-helical content and loss of binding properties and biological activity mediated through interaction of the analogues with both somatogen (3T3-F442A cells) and lactogen (PRL) receptors (NB2-11C cells). Truncation of 19-27 amino acids caused additional loss in activity, without further change in the secondary structure. Replacement of Leu28 by a more hydrophobic Phe has only minor, if any, effect on the bioactivity of bPL. Occasional point mutations due to polymerase chain reaction errors in several analogues did not seem to have any major effect on the hormone properties. It can thus be suggested that the N-terminal part of the nonhelical portion of bPL, which corresponds to the portion of the molecule that does not exist in growth hormones, is required for efficient binding to the lactogen (PRL) but not to the somatogen or unique bPL receptors. Removal of the N-terminal part of pBL changed the specificity of bPL by decreasing its PRL receptor-mediated activities and increasing its somatogen receptor-mediated activities.

Amino Acid Sequence↗

PubMed1991

Secondary structure of human interleukin-3.

1. The secondary structure of human interleuken-3 in solution was determined by circular dichroism spectroscopy. 2. The results were then compared with empirical secondary structure predictions based on primary sequence structure of the protein. 3. The two approaches are in extremently close agreement showing the protein to have 40% alpha-helix, 12% total beta-structure and 48% random coil content.

Amino Acid Sequence↗