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Biomedical subjects

C M Jones

Publications and source records attributed to C M Jones.

At least 109 records · Page 6Linked to original sources

Hydrogen peroxide, the effect on plaque and gingivitis when used in an oral irrigator.

The identification of plaque as the etiological agent in chronic gingivitis and the progression of chronic periodontitis, has intensified the search for effective chemical antiplaque agents to aid in the prevention and treatment of these diseases. To date, no ideal compound has been identified. Using the experimental gingivitis model, the effectiveness of a 1.5% hydrogen peroxide-containing oral rinse, applied as a conventional mouthrinse and in an oral irrigation device, was evaluated. The ability of the mouthrinse to inhibit the development of plaque and gingivitis in the two experimental groups, was compared with controls using a placebo rinse over two 7-day periods. At no time was there any statistical difference between either of the experimental groups and/or the placebo group in terms of gingival or plaque scores. This study concluded that a 1.5% hydrogen peroxide mouthwash was of no therapeutic value in the prevention or treatment of an experimental gingivitis, when used as a mouthrinse or in an oral irrigator.

Adolescent↗

Arachidonic acid metabolites produced by platelet-depleted human blood monocytes: a possible role in thrombogenesis.

The arachidonic acid metabolites produced by human peripheral blood monocytes were studied to determine which metabolites could have a role in thrombogenesis. Monocytes were found to be free of platelets by scanning electron microscopy and by measurement of 12-HETE. Human peripheral blood monocytes produce thromboxane as their major metabolite. Thromboxane levels reached a plateau at 12-16 hours of culture. Monocytes produced relatively little prostaglandin E2 or F2. In contrast to our control platelet preparation, neither A23187 (1-10 microM) nor exogenous arachidonic acid (0-40 microM) caused an increase in monocyte thromboxane B2. On the other hand, lipopolysaccharide (20 micrograms per ml), collagen (2.5 mg per 10(7) cells), and thrombin (5-10 units per ml) caused a two- to fivefold increase in monocyte thromboxane B2 in most donors but had no effect on prostaglandin F1 alpha levels. Blockage of thromboxane synthase by 1-benzylimidazole abolished thromboxane B2 production but did not increase prostaglandin F1 alpha. Finally, aspirin-treated platelets from a volunteer donor, which were refractory to 30 microM arachidonate, could be aggregated by isolated blood monocytes. Our data indicate that monocytes are capable of producing thromboxane in large amounts. The regulation of this increase, however, appears to be quite different from platelets. We postulate that monocytes may have a role in hemostasis by virtue of their ability to adhere at sites of vascular injury and release thromboxane, which may enhance platelet aggregation and thrombus formation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Drug-nutrient interaction counseling programs in upper midwestern hospitals: 1986 survey results.

A mail survey was conducted to determine the characteristics of drug-nutrient counseling programs provided to hospitalized patients. The survey population included general medical-surgical type hospitals with 175 or more bed capacity in five upper Midwestern states: Illinois, Iowa, Michigan, Minnesota, and Wisconsin. The average return from 289 surveys was 75%. A mean of 64% of responding hospitals provide patient counseling on drug-nutrient interactions. All statistical analysis was by chi-square. Calculations revealed that less than 50% of hospitals require a physician's order to provide drug-nutrient interaction counseling. More than 50% involve a registered dietitian in providing such counseling. The monoamine oxidase inhibitor drugs were cited most frequently as the group of drugs for which counseling was needed. Other drug groups for which patient counseling is needed include: diuretics, anticoagulants, tetracyclines, oral hypoglycemics, insulin, antihypertensives and/or cardiac drugs, antibiotics, and corticosteroids. Having the dietitian or other dietary personnel scan the patient chart was cited most often as the preferred method for detection of patients taking the drugs. A final statistical calculation revealed that there is no difference between teaching and nonteaching hospitals in the number providing a drug-nutrient counseling program.

Counseling↗

Characterization of a human monocyte cytotoxicity-inducing factor (MCF).

Recently, we reported a lymphokine, monocyte cytotoxicity-inducing factor (MCF), which is distinct from interferon-gamma (IFN-gamma). In this report, we provide further characterization of MCF. MCF is inactivated by chymotrypsin, but not trypsin, RNase, or DNase. The production of MCF is abolished in a dose-dependent manner by actinomycin D and is diminished by puromycin, and cycloheximide. Native MCF produced under serum-free conditions demonstrated charge heterogeneity with three species having isoelectric points at 2.7, 5.6, and 6.7 respectively, and two molecular weight species of 29 Kd and 14.7 Kd. MCF-activated monocytes were not only able to lyse both NK sensitive and resistant targets, but also secreted IL 1, but not TNF. In summary, MCF is a lymphokine distinct from TNF, IL 1, IL 2, the IFNs, and the CSFs, which is able to activate monocytes to lyse tumor targets.

Chymotrypsin↗

Influence of natural and recombinant interleukin 2 on endothelial cell arachidonate metabolism. Induction of de novo synthesis of prostaglandin H synthase.

We studied the effects of natural and recombinant human IL-2 (rIL-2) on secretion of prostacyclin (PGI2), vWf, and tissue-type plasminogen activator (tPA). IL-2 elicited a steady increase in PGI2 synthesis by cultured human umbilical vein endothelial cells (HUVECS) and bovine aortic endothelial cells but had no effect on vWf or tPA. Both purified natural IL-2 (nIL-2) and rIL-2 induced significant PGI2 synthesis. Substitution of the cysteine residue at position 125 of rIL-2 with serine or alanine led to loss of PGI2-stimulatory activity in HUVECS without affecting thymidine incorporation in lymphocytes. HPLC analysis of arachidonate metabolites detected predominantly 6 keto-PGF1 alpha (6KPGF1 alpha) peak. Treatment of cultured endothelial cells with cycloheximide and actinomycin D resulted in inhibition of 6KPGF1 alpha synthesis. The Western blot using a polyclonal antibody against PGH synthase revealed an increment in the 70-kD subunit of PGH synthase by nIL-2 and rIL-2, but not by alanine-substituted rIL-2. We conclude that IL-2 stimulated sustained PGI2 production by a mechanism that includes the de novo synthesis of PGH synthase. This mechanism for regulating AA metabolism probably has important physiologic implications.

6-Ketoprostaglandin F1 alpha↗

In vitro growth characteristics and chemosensitivities of endometrial cancer using a soft agar clonogenic assay.

A soft agar clonogenic assay was used to analyze 91 fresh human endometrial tumor samples for in vitro growth and chemosensitivities. Overall cloning success was 81%. Of the 75 samples adequate for drug testing (30 or more colonies per plate), histologic analysis demonstrated 36 adenocarcinomas, seven adenoacanthomas, ten adenosquamous carcinomas, nine mixed mesodermal sarcomas, seven carcinosarcomas, three papillary adenocarcinomas, and three clear-cell carcinomas. Mixed mesodermal sarcoma specimens demonstrated the most efficient growth, followed by the adenosquamous adenocarcinoma and adenoacanthoma samples. In vitro chemosensitivities were determined by colony inhibition resulting from continuous exposure of tumor cells to known achievable peak plasma and one-tenth peak plasma concentrations of a particular agent. The plating efficiency reflected the clinical virulence by cell type. Thus, we found that malignant endometrial tumors can be cloned in vitro, and the observed chemosensitivities reflect the relative clinical resistance of the tumors to these agents. Based on the high cloning success, this tumor type may be well suited as a model using in vitro soft agar cloning for new drug screening, evaluation of novel drug combinations, and studies of human tumor biology.

Antineoplastic Agents↗

Identification of a human monocyte cytotoxicity-inducing factor from T cell hybridomas produced from Sezary's cells.

Sezary's syndrome is a leukemic proliferation of OKT4+ lymphocytes. Sezary cells were isolated by differential centrifugation and fused to CEM.8azar.C, and HGPRTase-lacking clone of CEM. The hybrid cells were studied for their ability to produce soluble mediators of human monocyte cytotoxicity. The product of a single clone, FtF3, which bore the surface phenotype of Sezary cells, was characterized. Monocyte cytotoxicity-inducing factor (MCF) was found to be stable at pH 2 for 1 hr, unlike IFN-gamma, and was found to be more heat stable as well. Moreover, treatment of MCF with antisera to IFN-gamma, IFN-alpha or a combination of IFN-gamma and IFN-alpha failed to neutralize its biologic activity. MCF binds to matrix gel Red A. MCF eluted from this dye-ligand was found to have an apparent m.w. of 11,500 by gel filtration and 14,700 by SDS-polyacrylamide gel electrophoresis. MCF produced by hybridized Sezary cells appear to be neither IFN-gamma nor an altered molecular form of IFN-gamma, yet is a potent inducer of human monocyte cytotoxicity.

Animals↗

Catecholamine responses in fetal lambs subjected to hemorrhage.

We monitored plasma epinephrine and norepinephrine responses to hemorrhage of 20% of estimated blood volume in 11 chronically instrumented, unanesthetized fetal lambs. In addition, we performed control experiments--blood sampling but no hemorrhage--in five fetuses. Arterial blood gases, pH, mean arterial pressures, heart rates, and plasma norepinephrine and epinephrine levels were similar in both groups in the resting state. Arterial blood gases and pH did not change significantly during the experimental period in either group. Mean arterial pressure, heart rate, and plasma norepinephrine and epinephrine levels did not change in the control group during the experimental period. Hemorrhage was associated with a significant decrease in fetal mean arterial pressure, 39.8 +/- 1.2 to 29.6 +/- 2.1 mm Hg, and heart rate, 186 +/- 8 to 146 +/- 6 bpm (p less than 0.01 in both cases). There was a significant increase in plasma norepinephrine, 664.9 +/- 91.6 to 1384.8 +/- 216.7 pg/ml (p less than 0.02) and epinephrine, 224.6 +/- 43.6 to 681.7 +/- 199.0 pg/ml (p less than 0.01) with hemorrhage. These results demonstrate significant catecholamine responses to hypovolemia in the fetal lamb.

Animals↗

Successful treatment of pseudomyxoma peritonei of ovarian origin with cis-platinum, doxorubicin, and cyclophosphamide.

Pseudomyxoma peritonei is a rare disease characteristically secondary to mucin-producing adenocarcinomas of the ovary and appendix. Though, as a rule, not invasive or metastatic, death occurs secondary to gastrointestinal dysfunction. This is the first case of pseudomyxoma peritonei secondary to an ovarian primary possibly cured by systemic cis-platinum, doxorubicin, and cyclophosphamide.

Antineoplastic Combined Chemotherapy Protocols↗

Studies on the footpads of the polar bear (Ursus maritimus) and their possible relevance to accident prevention.

The incidence of slipping accidents is unknown, but accident and emergency departments in the United Kingdom probably treat over one million injuries per annum caused by slipping of the feet. Many injuries to farm livestock are caused by slipping. Previous research led to speculation that some animal species may have developed slip-resistant feet and the polar bear was chosen for a study of adaption to a slippery environment. Feet were photographed and a footpad was sectioned and examined by light and electron microscopy. Hardness of the footpads of two tranquillized bears was measured. The footpads were found to have a rough papillary surface overlying a soft dermis containing a dense network of collagen and elastic fibres. These findings support a hypothesis that shoe solings for use on an icy substrate should be soft with a hardness value in the region of 24 on the Shore A scale. The surface should be covered in conical projections having a mean diameter of 1 mm. Further work on the feet of animal species could lead to a better understanding of slip-resistance and reduce injuries to humans and livestock.

Accident Prevention↗

Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4.

A comparison of the sequence of the subunit of human alpha 2-macroglobulin (alpha 2M; 1451 amino acid residues) with that of murine complement component pro-C3 (1639 amino acid residues) reveals eight extended regions of sequence similarity. These regions contain between 19% and 31% identically placed residues and account for 75% and 67%, respectively, of the polypeptide chains of alpha 2M and pro-C3. Published sequence data for complement component C4 show that segments of this protein match well with corresponding stretches in alpha 2M and pro-C3. It is proposed that alpha 2M, C3 and C4, which all contain a unique activatable beta-cysteinyl-gamma-glutamyl thiol ester, have a common evolutionary origin and are homologous proteins. Several larger regions of low sequence similarity indicate the presence of structural domains in each of these proteins that specifically modify an underlying common gross structure. The quartets of basic residues in pro-C3 and pro-C4, at which cleavage takes place to produce the mature subunits of these proteins, and most of the residues forming the anaphylatoxin peptides of C3 and C4 (C3a and C4a) are absent in alpha 2M. In addition, C3 and C4 contain large portions, which extend beyond the COOH terminus of alpha 2M.

Amino Acid Sequence↗

Primary structure of human alpha 2-macroglobulin. I. Isolation of the 26 CNBr fragments, amino acid sequence of 13 small CNBr fragments, amino acid sequence of methionine-containing peptides, and alignment of all CNBr fragments.

The isolation of the 26 CNBr fragments from the identical Mr = 180,000 subunits of human alpha 2-macroglobulin is described. The fragments have been purified by combinations of gel chromatography, ion-exchange chromatography, high voltage paper electrophoresis, paper chromatography, and high performance liquid chromatography. The complete amino acid sequences of 13 small CNBr fragments have been determined. These fragments include CB1 (residues 1-9), CB3 (residues 79-98), CB4 (residues 99-128), CB9 (residues 442-477), CB10 (residues 478-497), CB13 (residues 644-650), CB14 (residues 651-665), CB15 (residues 666-674), CB16 (residues 675-690), CB19 (residues 937-945), CB20 (residues 946-954), CB24 (residues 1356-1362), and CB25 (residues 1363-1375). The fragments determined account for 200 of the 1451 residues of the subunits of alpha 2-macroglobulin. Most likely, Cys-6 of CB9 is bound to the corresponding residue in CB9 from another subunit, thus forming an interchain disulfide bridge in alpha 2-macroglobulin. Cys-1 of CB15 is bound to Cys-35 of CB12. CB15 contains a pair of Gln residues that can react covalently with amines in a factor XIIIa-catalyzed process (Gln-5 and Gln-6). CB16 contains the primary cleavage sites for proteinases in the bait region of alpha 2-macroglobulin (-Arg7-Val-Gly-Phe-Tyr-Glu-). CB20 contains the residues which in native alpha 2-macroglobulin presumably form an internal reactive beta-cysteinyl-gamma-glutamyl thiol ester (Cys-4 and Glx-7). Partial NH2- and COOH-terminal sequence data are given for the 13 large CNBr fragments. Complete or partial sequence determination of 19 methionine-containing peptides or variants thereof allow the alignment of all the CNBr fragments.

Amino Acid Sequence↗

Primary structure of human alpha 2-macroglobulin. II. Primary structure of eight CNBr fragments located in the NH2-terminal half of alpha 2-macroglobulin, accounting for 603 amino acid residues.

The amino acid sequence has been determined for eight medium-sized CNBr fragments from the NH2-terminal part of human alpha 2-macroglobulin. The fragments are: CB2 (10-78), CB5 (129-223), CB6 (224-295), CB7 (296-392), CB8 (393-441), CB11 (498-584), CB12 (585-643), and CB17 (691-775). These fragments account for 603 of the 1451 residues of the subunits of alpha 2-macroglobulin. CB2 contains two glucosamine-based carbohydrate groups attached to Asn-23 and Asn-38, and one internal disulfide bridge connecting Cys-16 with Cys-54. CB6 contains one glucosamine-based carbohydrate group attached to Asn-1 and two internal disulfide bridges (Cys-5 bound to Cys-53 and Cys-23 bound to Cys-41, respectively); Cys-32 is bound to Cys-16 in CB8. CB7 contains two glucosamine-based carbohydrate groups attached to Asn-78 and Asn-92, CB8 contains 1 Cys residue (Cys-16), bridged to Cys-32 of CB6. CB11 contains 1 Cys residue (Cys-75), bridged to Cys-58 of CB17. CB12 contains 1 Cys residue (Cys-35), bridged to Cys-1 of CB15. CB17 contains 1 Cys residue (Cys-58), bound to Cys-75 of CB11.

Amino Acid Sequence↗

Primary structure of human alpha 2-macroglobulin. V. The complete structure.

The primary structure of the tetrameric plasma glycoprotein human alpha 2-macroglobulin has been determined. The identical subunits contain 1451 amino acid residues. Glucosamine-based oligosaccharide groups are attached to asparagine residues 32, 47, 224, 373, 387, 846, 968, and 1401. Eleven intrachain disulfide bridges have been placed (Cys25-Cys63, Cys228-Cys276, Cys246-Cys264, Cys255-Cys408, Cys572-Cys748, Cys619-Cys666, Cys798-Cys826, Cys824-Cys860, Cys898-Cys1298, Cys1056-Cys1104, and Cys1329-Cys1444). Cys-447 probably forms an interchain bridge with Cys-447 from another subunit. The beta-SH group of Cys-949 is thiol esterified to the gamma-carbonyl group of Glx-952, thus forming an activatable reactive site which can mediate covalent binding of nucleophiles. A putative transglutaminase cross-linking site is constituted by Gln-670 and Gln-671. The primary sites of proteolytic cleavage in the activation cleavage area (the "bait" region) are located in the sequence: -Arg681-Val-Gly-Phe-Tyr-Glu-. The molecular weight of the unmodified alpha 2-macroglobulin subunit is 160,837 and approximately 179,000, including the carbohydrate groups. The presence of possible internal homologies within the alpha 2-macroglobulin subunit is discussed. A comparison of stretches of sequences from alpha 2-macroglobulin with partial sequence data for complement components C3 and C4 indicates that these proteins are evolutionary related. The properties of alpha 2-macroglobulin are discussed within the context of proteolytically regulated systems with particular reference to the complement components C3 and C4.

Amino Acid Sequence↗