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Biomedical subjects

H Jones

Publications and source records attributed to H Jones.

At least 91 records · Page 5Linked to original sources
PubMed1997

Role of nitric oxide on eosinophilic lung inflammation in allergic mice.

Nitric oxide (NO) is an important mediator of inflammatory reactions and may contribute to the lung inflammation in allergic pulmonary diseases. To assess the role of NO in pulmonary inflammation, we studied the effect of four nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, N(G)-monomethyl-L-arginine (NMMA) and L-N6-(1-Iminoethyl) lysine (L-NIL), on the influx of eosinophils into the bronchoalveolar lavage (BAL) fluid and lung tissue of antigen-challenged allergic mice. We also analyzed lung tissues for the presence of steady state mRNA for inducible nitric oxide synthase (iNOS) and iNOS protein. Furthermore, BAL fluid and serum were analyzed for their nitrite content. B6D2F1/J mice were sensitized to ovalbumin (OVA) and challenged with aerosolized OVA. The NOS inhibitors were given 0.5 h before and 4 h after the antigen challenge. OVA challenge induced a marked eosinophilia in the BAL fluid and lung tissue 24 h after challenge. The OVA-induced pulmonary eosinophilia was significantly reduced by L-NAME (10 and 50 mg/kg, intraperitoneally [i.p.]). The inactive isomer, D-NAME (50 mg/kg, i.p.) had no effect. When mice were treated with L-NAME (20 mg/kg, i.p.) and an excess of NOS substrate, L-arginine (200 mg/kg, i.p.), the OVA-induced pulmonary eosinophilia was restored. Treatment with aminoguanidine (0.4-50 mg/kg, i.p.) also reduced the pulmonary eosinophilia. Treatment with NMMA (2-50 mg/kg, i.p.) partially reduced the eosinophilia, but L-NIL (10-50 mg/kg, i.p.), a selective iNOS inhibitor, had no effect. L-NAME had no effect on the reduction of eosinophils in the bone marrow following OVA challenge to sensitized mice. OVA challenge to sensitized mice had no effect on iNOS protein expression or iNOS mRNA in the lungs or on the levels of nitrite in the BAL fluid. These results suggest that NO is involved in the development of pulmonary eosinophilia in allergic mice. The NO contributing to the eosinophilia is not generated through the activity of iNOS nor does NO contribute to the efflux of eosinophils from the bone marrow in response to antigen challenge. It is speculated that after antigen challenge, the localized production of NO, possibly from pulmonary vascular endothelial cells, is involved in the extravasation of eosinophils from the circulation into the lung tissue.

Animals↗
PubMed1997

Airway eosinophils, T cells, Th2-type cytokine mRNA, and hyperreactivity in response to aerosol challenge of allergic mice with previously established pulmonary inflammation.

Asthma is characterized by acute episodes of nonspecific airway hyperreactivity and chronic pulmonary inflammation exacerbated by stimuli including allergen exposure. In order to reproduce the physiologic and immunologic responses that occur in asthmatic patients, we have characterized a model of antigen-induced inflammation in which allergic mice (B6D2F1) that had been challenged once with aerosolized ovalbumin and had developed a pulmonary cellular infiltrate were rechallenged 1 wk later. Pulmonary inflammation in rechallenged mice was substantially greater than that in single-challenged mice. Eosinophils and activated-memory T cells (CD44+, CD45RBlo) in bronchoalveolar lavage (BAL) fluid accumulated to higher levels and with faster kinetics in response to the second challenge than in response to the first challenge. Eosinophils in lung tissue also accumulated to higher levels but with similar kinetics in response to the second challenge than in response to the first challenge. Similarly, interleukin (IL)-4 and IL-5 steady-state mRNA levels in lung tissue increased after the second challenge and were higher than those measured after a single challenge. Furthermore, treatment of mice with an anti-IL-5 monoclonal antibody 2 h prior to rechallenge inhibited antigen induced eosinophil accumulation in the lungs. In mice challenged twice, peak in vivo bronchoconstrictor responsiveness to acetylcholine was increased following the second challenge compared with that observed following the initial challenge. In contrast, ex vivo tracheal smooth muscle contractile responsiveness to acetylcholine was not altered. Although mucus accumulation and epithelial damage in pulmonary tissue were evident in mice challenged twice, these parameters were slightly reduced compared with those seen at similar times in mice challenged once. Therefore, although these mice exhibit only slight bronchial epithelial damage, the presence of significant inflammation and airway hyperreactivity to acetylcholine as well as slightly increased baseline reactivity demonstrate important similarities with the pathophysiology of asthma.

Administration, Inhalation↗
PubMed1996

Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II beta subunit (CSNK2B).

A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An approximately 220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes, has been analyzed for the presence of additional genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II beta subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product.

Base Sequence↗
PubMed1996

Autoantibody prevalence in chronic hepatitis B virus infection: effect in interferon alfa.

The most effective treatment of chronic hepatitis B virus (HBV) infection is interferon alfa (IFN-alpha), a potentially severe side effect of which is the induction of autoimmunity. To assess whether IFN-alpha causes clinical or serological autoimmune manifestations, we studied 61 children randomized to receive 5 MU/m2 of IFN-alpha three times per week for 12 weeks, with or without steroid priming or no treatment. Autoantibodies to antinuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC), liver kidney microsomal type 1, mitochondrial, liver cytosolic antigen, thyroid microsomal, and thyroid globulin were detected by standard techniques. Over a median of 4 years (range, 1-5 years) from randomization, no clinical signs of autoimmunity were observed. Autoantibody positivity for nuclei, smooth muscle, and/or gastric parietal cells was observed on at least one occasion in 42 of 61 children (69%), with no overall difference in the prevalence between patients treated with interferon alone (19 of 24 [79%]), steroids plus interferon (13 of 20 [65%]), or untreated controls (10 of 17 [59%]). There was also no difference in the autoantibody prevalence before, during, and at follow-up after cessation of treatment in both interferon-treated and interferon-untreated patients. Autoantibodies are common in chronic HBV infection, and their prevalence is uninfluenced by IFN-alpha.

Adolescent↗
PubMed1996

Effect of applanation tonometry on mean corneal curvature.

PURPOSE: To evaluate whether applanation tonometry affects corneal curvature and if so, the implications for intraocular lens power calculation. SETTING: Birmingham and Midland Eye Hospital, Birmingham, England. METHODS: Twenty-two patients attending the preoperative assessment clinic were enrolled in the study. Keratometry was performed immediately before, 1 minute after, and 10 minutes after standard Goldmann tonometry. Main outcome measures were mean corneal refractive power and its reproducibility (coefficient of repeatability). RESULTS: No clinically significant difference was noted between preapplanation and postapplanation readings (P = .6), and reproducibility was not significantly affected. CONCLUSION: The results indicate that corneal applanation before keratometry does not compromise the prediction of postoperative refraction.

Aged↗
PubMed1996

A radiation hybrid map of the human genome.

We have developed a panel of whole-genome radiation hybrids by fusing irradiated diploid human fibroblasts with recipient hamster cells. This panel of 168 cell lines has been typed with microsatellite markers of known genetic location. Of 711 AFM genetic markers 404 were selected to construct a robust framework map that spans all the autosomes and the X chromosome. To demonstrate the utility of the panel, 374 expressed sequence tags (ESTs) previously assigned to chromosomes 1, 2, 14 and 16 were localized on this map. All of these ESTs could be positioned by pairwise linkage to one of the framework markers with a LOD score of greater than 8. The whole genome radiation hybrid panel described here has been used as the starting material for the Genebridge4 panel that is being made widely available for genome mapping projects.

Animals↗
PubMed1996

Effect of plasma oncotic pressure on apolipoprotein levels in rats with Heymann nephritis.

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi). Infusion of dextran or albumin reduces lipid levels suggesting that reduced plasma pi plays a role in causing hyperlipidemia in the nephrotic syndrome. To determine whether apolipoprotein (Apo) levels were affected by pi, passive Heymann nephritis (HN) was created in 20 rats. Hyperoncotic (25%) human albumin or ficoll was infused continuously into each of 5 HN rats adjusted to maintain a plasma pi above 20 mm Hg. Either saline or a mixture of amino acids calculated to approximate those released from catabolized human albumin were infused into 5 HN as controls. Urinary rat albumin loss was not different between the 4 groups of HN. Plasma apo A-I, B and E were all increased significantly in saline and amino acid infused HN, but apo A-IV was decreased. Infusion of either albumin or ficoll normalized apo A-I, and apo E levels in HN even though proteinuria continued unabated. In contrast, apo B remained significantly elevated in HN infused with albumin, but was reduced to normal by ficoll. Fifteen non-nephrotic control animals were studied in 3 groups of 5 animals each; one receiving human albumin, one ficoll, both adjusted to increase plasma pi to supranormal levels, and a 3rd group received saline. In contrast to HN, plasma apo A-I, E, and B levels were unaffected by albumin or ficoll infusion in control animals. Ficoll caused a significant reduction in apo A-IV in both HN and control animals to subnormal levels, but albumin infusion was without effect. Reduced plasma pi, but not reduced plasma albumin is necessary for increased apo A-I, and E levels in the nephrotic syndrome. When plasma pi is normal extensive proteinuria does not increase plasma apo A-I or E levels. Factors other than an albumin concentration or pi, such as persistent urinary protein loss, play a role in establishing increased apo B containing lipoproteins in the nephrotic syndrome. Ficoll may cause changes in plasma lipoprotein levels by means other than its ability to increase plasma pi.

Animals↗
PubMed1995

Probing the protein-DNA interface of the EcoRV modification methyltransferase bound to its recognition sequence, GATATC.

The DNA contacts produced between the EcoRV modification methyltransferase and its recognition sequence, GATATC, have been determined. The enzyme's general location in a methylase/DNA/sinefungin ternary complex was evaluated by protection from exonuclease III digestion. Important phosphate contacts were resolved using N-ethyl-N-nitrosourea ethylation interference footprinting. Methylation protection and interference using dimethyl sulfate were employed to assess significant contacts to purinic bases. The protein-DNA interface was further probed using oligodeoxynucleotides containing base analogues within the GATATC sequence. Most of the experiments were carried out using hemimethylated sequences, i.e., having 6-methyladenosine at the methylation site in one of the strands. The monomeric methylase was found to bind to the DNA in two different orientations for the methylation of each strand. The enzyme approaches the DNA, predominantly from one "side", and makes most of its contacts in the major groove. In either of the two binding events contacts are made to the four phosphates NpNpNpGpA and the three bases GAT (where GAT represents the 5' half of the GATATC site) on both DNA strands. The phosphates and bases in the 3' ATC half are much less important. Although the contacts made to the equivalent locations on each strand are similar, they display a slight but consistent change dependent on which strand contains the 6-methyldeoxyadenosine. This strand variation shows completely reciprocal behavior, switching around exactly, depending entirely on the methylated deoxyadenosine location. It is this that provides evidence for the two binding modes. The results obtained are discussed in terms of possible models for the protein-DNA interface.

Adenosine↗
PubMed1995

Squamous intraepithelial neoplasia in an ovarian cyst, cervical intraepithelial neoplasia, and human papillomavirus.

A case of squamous intraepithelial neoplasia in an ovarian cyst in association with cervical intraepithelial neoplasia (CIN) III is described. In view of the association of human papillomavirus (HPV) and CIN, the possibility that HPV infection could be associated with similar changes in the ovary was postulated. The HPV genome was shown in formalin-fixed tissue of the cervical lesion by nonisotopic in situ hybridization (NISH) and by the polymerase chain reaction (PCR). However, HPV could not be shown in the ovarian lesion by NISH or PCR. On the basis of these findings there appears to be no association between HPV infection and squamous intraepithelial neoplasia in an ovarian cyst.

Adult↗
PubMed1995

The continuing ethnic-origins dimension of Australian immigration policy.

"Although Australia dismantled its ethnically discriminatory, immigrant-selection policy in the early 1970s, ethnicity remains--implicitly and unofficially--a significant consideration in its immigration policies and practices. The paper outlines the traditional ¿White Australia' policy before describing the operation and impact of the new selection policies and the associated official commitment to multiculturalism. The causes, regional pattern and acceptability of the modern Asianization of immigration are then assessed. The final section indicates how ethnic-origin preferences continue to operate in an apparently non-discriminatory selection policy, largely through the management of demand by placements of Australian migration officers in particular locations overseas."

Australia↗
PubMed1995

Effect of oncotic pressure on apolipoprotein A-I metabolism in the rat.

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi), urinary protein loss and hyperlipidemia. High-density lipoprotein (HDL) and the level of apo A-I, the principal apolipoprotein in HDL, is increased in nephrotic rats and rats with hereditary analbuminemia (NAR)--animals with virtually no albumin in plasma and reduced plasma pi, but without proteinuria, suggesting that urinary protein loss is not responsible for increased plasma apo A-I levels. We conducted these studies to determine the mechanism responsible for increased plasma apo A-I levels in the nephrotic syndrome and NAR and to determine whether reduced plasma pi or albumin was responsible for increased apo A-I. We first measured the clearance of 125I apo A-I HDL in NAR and rats with passive Heymann nephritis (HN) compared with normal Sprague Dawley (SD) control. Both the clearance of apo A-I and fractional apo A-I turnover rate (FTR) were significantly reduced both in HN (7.40 +/- 2.18% plasma pool/hr) and NAR (5.63 +/- 1.12) compared with SD (9.87 +/- 0.75). Total apo A-I turnover rate, which in steady state equals apo A-I synthesis rate, was also significantly increased in both HN (487 +/- 127 micrograms/100 g body weight/hr) and NAR (253 +/- 16), compared with SD (216 +/- 19). Thus decreased apo A-I catabolism and increased synthesis both contributed to increased apo A-I levels in HN and NAR. We then infused either f3p4roncotic human albumin or ficoll into two additional groups of HN for days in quantities sufficient to maintain plasma pi within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A locking endurance test for hinged sections of removable partial dentures.

In this study an apparatus is described that will open and close a hinged section of a removable partial denture. A metal framework based on a "swinglock" type of hinge and latch design was constructed. An electric motor provided the drive for the opening and closing mechanism, which when operated set the device in motion. The device and results of a test run of 12,000 opening and closing operations are discussed.

Dental Clasps↗
PubMed1995

Non-iron mediated alteration in hepatic transferrin gene expression in the nephrotic rat.

Both transferrin and the iron it carries are lost in the urine in the nephrotic syndrome. Patients may develop hypochromic microcytic anemia and synthesis of transferrin, a protein regulated in large part by iron availability, is increased. Transferrin synthesis has also been reported to be increased in liver slices from rats with hereditary analbuminemia, and their plasma transferrin levels are increased, suggesting that transferrin synthesis may be stimulated by processes other than iron depletion in this hypoalbuminemic condition. Transferrin metabolism was studied in rats with Heymann nephritis (HN), in a strain of Sprague-Dawley (SD) rats with hereditary analbuminemia [Nagase analbuminemic rats (NAR)], and in normal SD rats. Plasma transferrin concentration and mass was decreased significantly in HN, but increased in NAR. Transferrin synthesis was increased both in NAR (measured either as the disappearance of [125I] labeled transferrin or as the incorporation of [3H] phenylalanine) and in HN (incorporation of [3H] phenylalanine). The fractional rate of transferrin catabolism was unchanged in NAR. Thus transferrin mass was increased in NAR entirely as a consequence of increased synthesis. Transferrin and albumin synthesis correlated with one another in both HN and SD (P < 0.001). Transferrin mRNA was increased in both HN and NAR and was unaffected by administration of iron to HN. Hepatic transferrin and albumin mRNA levels were also correlated positively in HN and SD, suggesting that increased hepatic synthesis of both proteins might be responding to the same stimuli. Transferrin gene transcription was increased in both HN and NAR and was unaffected by administration of iron to HN. Transferrin mRNA was not increased in the testis in either HN or NAR, suggesting that augmentation in transferrin gene expression is driven by a non-iron dependent process and is confined to the liver.

Albumins↗
PubMed1995

Benign myoepithelioma of the salivary glands: a true entity?

Myoepithelioma is a rare neoplasm of the salivary glands which is now recognized as an individual entity in the revised WHO classification. In this study, eleven benign tumours are presented. Most patients gave a history of a slowly enlarging mass, which was cured by surgical excision. However, one case recurred several times over 50 years, and another still has residual tumour and removal is not possible. The histological appearances included solid, myxoid and reticular growth patterns, composed predominantly of spindle shaped or plasmacytoid (hyaline) cells. Many of the tumours also contained occasional small ducts. All 11 tumours were positive for S-100 protein, variable reactions being seen for various other antigens--keratins, human milk fat globulin, carcinoembryonic antigen, alpha smooth muscle actin and vimentin. It is probable that myoepithelioma constitutes one end of a biological spectrum which also includes pleomorphic adenoma and some (non-membranous) basal cell adenomas. In practice, however, we still advocate retention of myoepithelioma as a separate diagnostic category, on the grounds that it has a range of distinctive microscopic appearances and poses its own unique problems in correct identification.

Adult↗