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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 235 records · Page 13Linked to original sources

Leucocyte common antigen expression on T cells in normal and inflamed human gut.

The expression of the 220,000 MW (p220) glycoprotein component of the leucocyte common antigen (LCA) family by intestinal mucosal lymphocytes was studied using the CD45R monoclonal antibody WR16. In normal intestine, a proportion of CD3+ mucosal T cells were WR16+ and this population resided predominantly in the mid-villus and crypt region of lamina propria. In the inflammatory infiltrates of both coeliac disease and Crohn's disease the CD3+, WR16+ population was markedly reduced. The monoclonal antibody UCHL1 identifies the 180,000 MW member of the LCA family and is expressed on T cells and in macrophages. CD3+ lymphocytes expressing this marker were widespread in normal lamina propria and epithelium. In contrast with WR16, UCHL1+ cells remained at a high level in coeliac disease and Crohn's disease. Our results support the view that loss of the p220 molecule occurs upon T-cell activation in inflammation.

Antigens, Differentiation↗

The effect of sulphasalazine on the in vitro activation of human peripheral blood mononuclear cells by phytohemagglutinin P.

The in vitro action of sulphasalazine, BW 755-C and indomethacin on phytohemagglutinin P-induced human peripheral blood mononuclear cell activation was studied. Sulphasalazine increased, while indomethacin and BW 755-C decreased, prostaglandin E2 (PGE2) accumulation in activated cultures. When used together with indomethacin or BW 755-C, sulphasalazine did not counteract the inhibition of PGE2 caused by the other two. Sulphasalazine inhibited phytohemagglutinin P-induced cell activation in a concentration-dependent manner even when used together with indomethacin or BW 755-C. BW 755-C inhibited cell activation at 350 microM, whereas at 11 microM it only increased sulphasalazine-induced inhibition. The implications of these findings on the etiopathology of inflammatory bowel disease are discussed.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Texas will see red during Drug Free America Week.

Betty Haisten is the living image of refinement. But that doesn't stop her from cornering the manager of a cafeteria in her hometown of Beaumont and putting pressure on him to use his facility as a distribution point for red ribbons encouraging patrons to "Join me--I'm drug free." She is a woman with a cause, a moving force behind Drug Free America Week in Texas. And, with the members of the nation's largest medical association auxiliary and their spouses behind Mrs. Haisten, Texas will see red--red ribbons--Oct 22-29. The Texas Red Ribbon Campaign is designed to establish a coalition in every community in support of drug-free lifestyles. This article describes how Texas Medical Association and TMAA are supporting the campaign's goal.

Adolescent↗

The devil or the sea? Transfer regs create a dilemma.

With the advent of strict federal regulations, physicians considering whether to transfer patients seeking emergency treatment can find themselves between the devil and the deep blue sea. Do they spar with the diabolical guidelines and follow their best medical instincts and training? Or, do they abandon their instincts and training and depend on a regulatory life preserver to keep their heads above water? Victoria obstetrician/gynecologist Michael L. Burditt, MD, embodies this unenviable dilemma. After he ordered the transfer of an indigent pregnant patient from Victoria to Galveston, the federal government accused him of knowingly making an inappropriate decision to transfer. Dr Burditt appealed the government's ruling, and the confrontation eventually led him to the courtroom in the nation's first test of the 1986 law that prohibits patient "dumping." Dr Burditt came close to settling the case, but, with assistance from the Texas Medical Association, the Victoria-Goliad-Jackson County Medical Society, and the American Medical Association, he's still in the fight. At the heart of the case is the issue of guaranteeing physicians due process in the review system for transfers. (Due process, the physician's right to be heard before fines or sanctions are imposed, is guaranteed in Medicare's quality review procedures, but not in transfer reviews). The case is in the hands of an administrative law judge, who is expected to hand down a decision in June. This article examines Dr Burditt's case in light of developments that brought hospital transfers under federal scrutiny.

Female↗

Trouble on the border: international health problems merge at the Rio Grande.

"Mosquitoes don't have green cards", Laurance N. Nickey, MD, says. That is Dr Nickey's way of saying that disease and environmental pollutants do not recognize the political boundary that separates Texas from Mexico. Dr Nickey, director of the El Paso City-County Health District and chairman of Texas Medical Association's Council on Public Health, is a native and lifelong resident of the city. He is an expert on the public health problems that plague El Paso and the other cities along the international border, all of which are exacerbated by abject poverty and a burgeoning population. Dr Nickey works tirelessly to bring these problems to the attention of Texas physicians, legislators, and other opinion leaders because, as he says, "Out here, we feel like we're the forgotten Texans."

Communicable Disease Control↗

Help wanted: nurses, nurses, nurses!

Want ads with a desperate tone are filling classified advertising sections of newspapers throughout Texas. The state's shortage of nurses is there for all to see, spelled out in big, bold type. "Take a new direction." "Built for the future. Designed for your career.... Take your career into the next century." Hospitals lure nurses with a choice of working hours, subsidized transportation, tuition reimbursement, educational programs, bonus programs, relocation assistance, temporary housing, and more. Still, the problem persists. In the worst case scenario, it has reached crisis proportions. In May 1988, in a highly publicized move prompted by the shortage, one Texas hospital was turning away ambulance-borne patients from its emergency room and came to the brink of losing Medicare and Medicaid funding. The Texas Legislature's Special Committee on Post-Secondary Medical, Dental, and Allied Health Education has documented the administrator's problem. According to the committee's report, issued in December 1988, "There is one Texas registered nurse for every 418 people in the general population; the national average is one RN for every 200 people." Physicians, nurses, and hospital administrators are vitally concerned with the situation's serious implications for the quality of patient care, and all three groups are searching for solutions. The following article explores the history, causes, and proposed solutions for the problem.

Humans↗

Fungal keratitis in contact lens wearers.

In a retrospective review from 1972 through 1987 of patients with microbial keratitis, fungal infection occurred in four (4%) of 90 cosmetic or aphakic contact lens wearers and in four (27%) of 15 patients using a therapeutic soft contact lens. Predisposing factors included improper lens care by the refractive lens wearers and a chronic epithelial defect with topical corticosteroid use among the therapeutic lens wearers. The responsible organisms in the refractive lens group were Fusarium solani (two patients) and Cephalosporium and Paecilomyces (one patient each), and in the therapeutic lens group Candida (three patients) and Aspergillus (one patient). Filamentous fungi were more likely to be associated with cosmetic or aphakic lens wear, whereas yeasts were more frequently found with therapeutic lens use.

Adult↗

Effect of inhibitors of S-adenosylmethionine decarboxylase on polyamine content and growth of L1210 cells.

Analogues of S-adenosylmethionine that were designed as inhibitors of S-adenosylmethionine decarboxylase were tested for their abilities to inhibit the purified enzyme from rat prostate. The most potent inhibitors were 5'-deoxy-5'-[N-methyl-N-[2-(aminooxy)ethyl]amino]adenosine (MAOEA) and 5'-deoxy-5'-[N-methyl-N-(3-hydrazinopropyl)amino]adenosine (MHZPA), which had I50 values of 400 nM and 70 nM, respectively, when added directly to the assay medium under standard conditions. These compounds were irreversible inactivators of the enzyme, and more than 95% of the activity was lost within 15 min of exposure to 5 microM MAOEA or 0.5 microM MHZPA. Both inhibitors led to a large reduction in the content of decarboxylated S-adenosylmethionine in L1210 cells and to a substantial decrease in the production of 5'-(methylthio)adenosine by these cells. These results are consistent with their bringing about an inhibition of S-adenosylmethionine decarboxylase activity in the cell which leads to a reduction in the synthesis of spermidine and spermine. Analysis of the polyamine content in L1210 cells exposed to 100 microM MAOEA or 50 microM MHZPA showed that this was the case and that putrescine levels were greatly increased while spermidine and spermine content declined. The combined application of 100 microM MAOEA and 5 mM alpha-(difluoromethyl)ornithine (an ornithine decarboxylase inhibitor) to L1210 cells completely prevented the synthesis of putrescine, spermidine, and spermine for up to 48 h. The reduction in polyamine content brought about by MHZPA or MAOEA could be partially prevented by the addition of decarboxylated S-adenosylmethionine to the culture medium. These inhibitors also brought about an inhibition of cell growth which could be reversed by the addition of spermidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Effect of plasma protein binding on elimination of taurocholate by isolated perfused rat liver: comparison of venous equilibrium, undistributed and distributed sinusoidal, and dispersion models.

In the past, various models have been developed to allow better characterization of the hepatic elimination of substrates from plasma. In this study we investigated the applicability of the venous equilibrium, undistributed sinusoidal, several distributed sinusoidal, and dispersion models to the steady state elimination of sodium taurocholate by the isolated perfused rat liver. Rat livers were perfused with 24-14C-taurocholate (sodium salt) at a concentration of 25 microM (specific activity 500 microCi/mmole) in a single-pass design (n = 7) or at a rate of 0.5 mumol/min (specific activity 40 microCi/mmole) into the portal vein in a recirculating design (n = 5). In single-pass experiments, the changes in hepatic venous outflow concentration (C0) with changes in unbound fraction of taurocholate (fu) from 0.09 to 1.0 were fitted better by the venous equilibrium model, by the dispersion model, and by a distributed model in which heterogeneity in both hepatic blood flow (Q) and intrinsic clearance (CLint) was defined by separate density functions. The very large value of dispersion number (DN greater than 10(7] yielded by the dispersion model is consistent with a high degree of axial mixing of blood within sinusoids. The large coefficients of variation (0.7-232) for the density functions describing the transverse heterogeneity of Q and CLint obtained with the Q/CLint-distributed model were consistent with a large degree of heterogeneity in Q and CLint within the liver. In recirculation experiments, the steady state unbound concentration of taurocholate in the reservoir (Cuss) was independent of fu (range 0.05-0.9). This finding was not predicted by the undistributed sinusoidal model, but was in keeping with the venous equilibrium model, with the dispersion model, and with the Q/CLint-distributed model. Therefore, there is no need to invoke cell surface-mediated dissociation of albumin-ligand complexes in hepatic taurocholate uptake. As the dispersion and Q/CLint-distributed models are conceptually plausible and operationally accurate, it may be time to relinquish the venous equilibrium model, which, though operationally accurate, is conceptually flawed.

Animals↗

The treatment of gastric ulcer with antisecretory drugs. Relationship of pharmacological effect to healing rates.

Published clinical trials (N = 56) of antisecretory drugs in the treatment of benign gastric ulcer were reviewed. Composite healing rates for various drug regimens were calculated using a method previously described for duodenal ulcer. Healing rates were compared with data on suppression of intragastric acidity to see if any relationship was evident. No significant correlations between the two existed, unless placebo data were included in the analysis. Correlations were stronger with suppression of total 24-hr rather than nocturnal acidity. Using Williams' method for assessing trends, it was found that an increase in antisecretory effect is not associated with a concomitant increase in healing rates. Duration of medical treatment is the single most important factor in healing of benign gastric ulcer; healing rates for all drug regimens and placebo show a consistent increase with prolongation of treatment.

Anti-Ulcer Agents↗

Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B.

Forty-five patients with chronic hepatitis B were entered into a randomized controlled trial of recombinant human alpha-interferon therapy. All patients had hepatitis B surface antigen in serum for at least 1 yr and had stable serum levels of both hepatitis B virus deoxyribonucleic acid and hepatitis B e antigen. During the 4-mo period of therapy, 10 of 31 (32%) treated patients and only 1 of 14 (7%) control patients became negative for serum hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase. All 10 patients who became negative for serum hepatitis B virus deoxyribonucleic acid subsequently had a marked improvement in serum aminotransferase activities and lost hepatitis B e antigen from serum, and 9 of them had improvement in liver histology. Comparison of responders to nonresponders indicated that female sex and a high initial level of serum aspartate aminotransferase correlated best with response to interferon therapy. These findings indicate that a 4-mo course of recombinant alpha-interferon can induce a remission in disease in approximately one-third of patients with chronic hepatitis B.

Adolescent↗

Phenotypic and genotypic heterogeneity of peripheral T-cell lymphoma.

A series of 21 phenotypically characterised T-cell lymphomas histologically defined as lymphocytic, lymphoblastic, immunoblastic, AILD type, pleomorphic, T-zone and Lennert's T-cell lymphoma, were investigated for T-cell receptor (TcR) and immunoglobulin (Ig) gene rearrangements. Phenotypic analyses of frozen sections and cell suspensions were heterogeneous and in many cases no single T-cell marker recognised all of the malignant cells. Data derived by staining with antibodies reactive with antigens in paraffin embedded tissue were consistent with T NHL in all cases except lymphoblastic lymphoma. TcR gene rearrangements were observed in lymphocytic, lymphoblastic and immunoblastic lymphoma, however, in the remaining 14 phenotypically and histologically defined peripheral T-cell lymphomas, 2 showed rearrangement of TcR gamma and beta genes consistent with T NHL and 2 showed Ig JH rearrangements only, suggestive of either reactive T-cell populations masking cryptic disease or presence of tumour populations with aberrant gene rearrangement and expression of T lineage antigens. No Ig or TcR gene rearrangements were found in the remaining 10 cases, in which morphologically identifiable tumour cells comprised 10-90% of the cell population. In 3/6 cases tested some CD3 positive cells failed to stain with WT31 or beta F1, monoclonal antibodies that recognise determinants on combined TcR gamma beta or TcR beta chains respectively. Whether these cases represent tumours arising from an undetermined cell of origin or polyclonal expansions of T-cells remains to be determined. Our results confirm the phenotypic heterogeneity of histologically defined peripheral T-cell lymphoma and indicate that in these particular histological subtypes gene rearrangement analysis can also yield heterogeneous results which may be unhelpful in determining cell lineage and clonality.

DNA Probes↗

An immunohistochemical study of lymphoid tissue in human endometrium.

An immunohistochemical study of human endometrium has been carried out using a panel of monoclonal antibodies directed against T cells and their subsets, B cells, macrophages, natural killer cells, dendritic reticulum cells, human leucocyte antigen class II, leucocyte common antigen, and proliferating cells. Normal endometrium at different phases of the menstrual cycle and abnormal endometrium were examined and the number of cells of each type was counted. Throughout the menstrual cycle, T-lymphocytes and macrophages form a significant proportion of the normal stromal population (mean 4 and 5%, respectively). They are seen in basal aggregates, scattered through the stroma, located between epithelial cells, and in gland lumina. B cells are rare except in basal aggregates. In late secretory phase, large numbers of T cells of an unusual phenotype appear (mean 16% stromal cells). These bear early (OKT 11 and 3A1) but not mature (UCHT 1, OKT 4, and OKT 8) T cell markers. They correspond to stromal granulocytes, which are prominent in paraffin-embedded tissue at this phase of the cycle.

Cell Count↗

The immunoglobulin E- and calcium-dependent release of histamine and eicosanoids from human dispersed mastocytosis spleen cells.

The clinical features of systemic mastocytosis have been ascribed to mast cell-dependent mediators, but there have been no studies of their release from isolated cells. We have investigated the release of histamine and eicosanoids from isolated spleen cells obtained from tissue of a mastocytosis patient undergoing therapeutic splenectomy. Dispersed cell preparations contained lymphocytes 65.9%, monocytes/macrophages 22.3%, neutrophils 9.9%, mast cells 1.1%, and eosinophils 0.8%; upon challenge with 0.1-3.0 microM A23187 they released histamine much greater than PGD2 greater than TXB2 greater than LTB4 greater than LTC4 approximately equal to LTD4 greater than LTE4. With immunological activation of passively sensitized cells, histamine and PGD2 release had similar dose-response characteristics, but TXB2, LTC4, LTD4, and LTE4 release differed in reaching maximum at 50 micrograms/ml and declining at 125 micrograms/ml anti-human IgE. Percoll centrifugation separated most of the histamine-containing cells to the middle of the gradient, but they were refractory to release with 0.3 microM A23187 or 50 micrograms/ml anti-IgE. Spontaneous release of histamine from these cells was not abnormally high (1.3%-4.5%). Electron microscopy of tissue sections revealed large numbers of mast cells with empty granules. It is possible that the refractory cells observed are such mast cells where intracellular histamine is no longer granule-associated. Most net histamine and PGD2 release was confined to cells at the bottom of the gradients (1.078-1.09 g/ml), although some release of PGD2 occurred near the top (1.05-1.058 g/ml). There was a significant correlation between the net release of histamine and PGD2 with both immunological (r = 0.92; n = 16) and A23187 (r = 0.97, n = 14) activation. These studies provide evidence for a link between PGD2 and histamine release in mastocytosis spleen cells.

Adult↗