PubMed Health⌕ Search

Biomedical subjects

W D Jones

Publications and source records attributed to W D Jones.

At least 19 recordsLinked to original sources
PubMed1993

Tuberculosis in a correctional facility.

BACKGROUND: After the identification of five suspected cases of tuberculosis (TB) in a Nassau County (New York) jail during a 3-week period, an epidemiologic investigation was begun to document the number of cases of TB infection and disease associated with the jail, the characteristics of current or former inmates with TB disease, and the factors contributing to TB transmission in the jail. METHODS: The county TB register was matched against the inmate files of the jail. Medical records from hospitals, the health department, and the jail were then reviewed. All inmates in the jail were skin tested during a mass screening. RESULTS: From January 1, 1988, through March 16, 1990, of 205 TB cases in the county, 49 (24%) were associated with the jail. Forty of the cases occurred among current or former inmates, one in a corrections officer, and eight among community contacts of inmates. The 40 inmates with TB were predominantly nonwhite (75%), unmarried (80%) men (90%), with a median age of 32 years. Twenty-three (58%) had a history of injecting drug use, and 14 (35%) were known to be seropositive for the human immunodeficiency virus. Thirty (75%) of the inmates had culture-confirmed pulmonary TB. Five (29%) of 17 Mycobacterium tuberculosis isolates had the same phage type and DNA fingerprint, which was consistent with transmission of infection within the jail. The mass screening revealed that 374 (20%) of 1855 inmates were tuberculin positive. CONCLUSIONS: Without an effective program of TB control, jails can act as reservoirs of disease for inmates and staff, and for the community into which the inmates are released.

Adult↗
PubMed1992

Inhibition of experimental metastasis and cell adhesion of B16F1 melanoma cells by inhibitors of protein kinase C.

Phorbol esters which activate protein kinase C (PKC) have been shown to enhance experimental lung metastasis. Therefore, it was reasoned that inhibitors of PKC might also modulate metastasis. We have investigated this possibility using a PKC inhibitor, MDL 27,032 [4-propyl-5(4-pyridinyl)-2(3H)-oxazolone], as well as staurosporine and H-7. Treatment of B16F1 murine melanoma cells with MDL 27,032 for 24 h in culture and subsequent i.v. injection of the cells into mice resulted in greater than 90% inhibition of lung metastasis. Inhibition of metastasis was time dependent, with 90% of maximum inhibition occurring by 8 h of incubation. The 50% inhibitory concentration (IC50) for inhibition of metastasis with MDL 27,032 was 7 microM, a value similar to that for the inhibition of B16F1 membrane-associated PKC (IC50 = 13 microM) but not cytosolic PKC (IC50 = 54 microM). B16F1 cells treated with MDL 27,032 for 24 h were less adherent than untreated cells to extracellular matrix/basement membrane proteins. Adhesion to fibrinogen and collagen IV was inhibited (IC50 = 6 microM and 48 microM, respectively) by MDL 27,032, whereas adherence to laminin and fibronectin was not affected, indicating that the drug affects specific adhesion molecules. MDL 27,032-treated cells were also found to be less adherent than untreated cells to human umbilical vein endothelial cells. The phosphorylation of an 80-kDa B16F1 cell plasma membrane protein was stimulated under conditions known to stimulate PKC activity, and MDL 27,032 inhibited this phosphorylation in a dose-dependent manner. MDL 27,032 was more potent than H-7 for the inhibition of metastasis but was significantly less potent than staurosporine. These results support the hypothesis that there is a critical role for PKC-mediated phosphorylation of cell surface adhesion receptors in metastasis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Inhibition of angiogenesis in vitro and in ovo with an inhibitor of cellular protein kinases, MDL 27032.

Protein kinase C (PKC) was implicated as an important positive regulator of angio-genesis by studies showing that tumor promoting phorbol esters, which activate PKC, stimulate angiogenesis both in vitro and in vivo. Therefore, inhibitors of PKC might be expected to block angiogenesis. MDL 27032 [4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone], an inhibitor of cellular protein kinases, prevented capillary-like tube formation by human umbilical vein endothelial cells (HUVEC) on basement membrane preparations, an in vitro model for angiogenic activity. MDL 27032 had an IC50 = 50 microM, whereas MDL 27044, the 4-methyl analog of MDL 27032, was less effective (IC50 greater than 100 microM). This selectivity was reflected in the relative abilities of the two compounds to inhibit PKC and protein kinase A (PKA) activity prepared from HUVEC, and also to inhibit the basic fibroblast growth factor stimulated proliferation of HUVEC. MDL 27032 (0.3 microgram/egg) also significantly inhibited neovascularization in yolk sac membranes of developing chick embryos, whereas MDL 27044 added at concentrations up to 3 micrograms/egg was not inhibitory when compared with vehicle treated controls. Adhesion of HUVEC to individual extracellular matrix proteins, including laminin, fibronectin, and fibrinogen, but not to the mixture of matrix components or collagen type I and IV, was inhibited after treatment with MDL 27032. These studies suggest that MDL 27032, may have potential as an anti-angiogenic agent because it disrupts both formation of tube-like structures by HUVEC on Matrigel and normal neovascularization in ovo. This inhibition may in part be due to altered cellular interactions with the extracellular matrix.

Animals↗
PubMed1992

Separation of Mycobacterium bovis BCG from Mycobacterium tuberculosis and Mycobacterium bovis by using high-performance liquid chromatography of mycolic acids.

Profile analysis of mycolic acid ester patterns of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium bovis bacillus Calmette-Gúerin (BCG) using high-performance liquid chromatography indicated that separation of BCG from M. tuberculosis and M. bovis by elution and relative retention times is possible. Mycolic acid patterns of BCG eluted from the column 0.5 min before M. tuberculosis or M. bovis, resulting in relative retention times for two peaks not seen in the pattern of M. tuberculosis or M. bovis. Identification was confirmed by phage typing, which has been the standard procedure for confirmation of BCG strains. These results showed that high-performance liquid chromatographic analysis of mycolic acid esters can be used in the mycobacterial reference laboratory for separation of BCG from M. tuberculosis and M. bovis.

Bacteriophage Typing↗
PubMed1991

Relapse of tuberculosis in a patient with the acquired immunodeficiency syndrome despite 12 months of antituberculous therapy and continuation of isoniazid.

A 33-year-old man with AIDS and pleuro-pulmonary tuberculosis was treated with a combination of antituberculous medications for 12 months and with continuation of isoniazid. A total of 2 months after completing combination therapy the patient developed fever, malaise, and anorexia. Mycobacterial blood cultures grew M. tuberculosis and the patient improved with the readministration of rifampicin and pyrazinamide. Phage typing of the patient's isolates of M. tuberculosis confirmed that he had experienced a relapse and not a reinfection. The patient had received 5 months of his treatment while hospitalised. We believe he was compliant with therapy outside the hospital because he attended all of his clinic appointments. Follow-up studies of HIV-infected patients with tuberculosis are therefore needed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

MDL 27,032 relaxes vascular smooth muscle and inhibits protein kinase C.

The smooth muscle relaxant effect of MDL 27,032, 4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone, was studied in vitro using strips of femoral arteries and saphenous veins from dogs and trachea from guinea pigs. MDL 27,032 (10(-6)-10(-3) M) produced a concentration-dependent relaxation of arterial and venous strips contracted by carbachol. MDL 27,032 also antagonized contractions of arterial and venous strips produced by phorbol 12,13-dibutyrate (PDB), a protein kinase C activator, both in normal-Ca2+ and zero-Ca2+ medium. The compound inhibited protein kinase C in soluble extracts prepared from saphenous veins of dogs, with an IC50 value of 36.6 microM. MDL 27,032 was more effective against the contractions produced by phenylephrine and serotonin than by KCl in arteries, but no such selectivity was noted in veins. MDL 27,032 (10(-3) M) also inhibited accumulation of inositol phosphates in femoral artery but not in saphenous vein, and this effect may have contributed to the arterial-relaxant effect. Because the vascular smooth muscle relaxant effect of MDL 27,032 was endothelium independent, did not involve blockade of alpha-adrenoceptors or inhibition of cyclic nucleotide phosphodiesterases, stimulation of beta-adrenergic receptors, stimulation of adenosine A2-receptors, or activation of K+ channels, these data suggest that the relaxant effects of MDL 27,032 primarily involve inhibition of protein kinase C.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Suppression of interleukin-1 beta and LDL scavenger receptor expression in macrophages by a selective protein kinase C inhibitor.

A human monocytic cell line, THP-1, stimulated with 40 nM phorbol myristate acetate (PMA), differentiated to macrophage-like cells, and exhibited increased expression and release of interleukin-1 beta and expression of acetylated low density lipoprotein (ac-LDL) receptors. A selective inhibitor, MDL 29,152 (4-propyl-5-(4-quinolinyl)-2(3H)-oxazolone) was used to show that this induction required activation of protein kinase C. MDL 29,152 acts in the catalytic domain of protein kinase C and is at least 200-fold selective for protein kinase C over cAMP-dependent protein kinase in THP-1 cells. MDL 29,152 (50 microM) reduced levels of interleukin-1 beta mRNA in PMA-stimulated cells by 76% and eliminated detectable interleukin-1 beta in the media. Flow cytometric analysis showed that 48 h after THP-1 activation, approximately 50% of the cells expressed ac-LDL receptors, while in the presence of 100 microM MDL 29,152, less than 5% of the cells expressed receptors. The relationship between THP-1 differentiation and protein kinase C activation was determined by following the expression of the cell surface antigen MO-1. Expression of MO-1 antigen increases as monocytes differentiate to macrophages. After 48 h of phorbol activation, 90% of the THP-1 population was MO-1-positive; less than 16% of the population was MO-1-positive when 100 microM MDL 29,152 was present. By dual analysis, it was found that within the differentiated, MO-1-positive population, only approximately 50% of the cells also expressed ac-LDL receptors. Based on these findings, we conclude that protein kinase C promotes processes important in THP-1 activation and differentiation to macrophage-like cells including interleukin-1 beta expression and secretion, ac-LDL receptor and MO-1 expression.

Cell Differentiation↗
PubMed1990

Geographic distribution of phage types among cultures of Mycobacterium tuberculosis. II. Cultures from India and South Africa.

Mycobacterium tuberculosis cultures obtained from India and South Africa were phage-typed to determine distribution patterns according to phage type in these two geographic locations. Of the 74 Indian strains, 14.9% were type 1, 32.4% were type 2, 28.4 were type 7, and 24.3% were type 8, whereas of the 78 South African strains, 20.5% were type 1, 47.5% were type 2, 1.3% were type 4, 11.5% were type 7, 19.2% were type 8. The phage types were then subdivided according to the lytic patterns produced by the six auxillary phages. The phage type distribution in the Indian and South African strains was compared with the type distribution in cultures from the United States and Southeast Asia, and differences were found in the four widely separated geographic areas.

Asia, Southeastern↗
PubMed1990

MDL 27,032 [4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone], an active site-directed inhibitor of protein kinase C and cyclic AMP-dependent protein kinase that relaxes vascular smooth muscle.

MDL 27,032 [4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone] is a novel vasodilator whose mechanism of action has not been elucidated. We investigated whether smooth muscle relaxation by MDL 27,032, in vitro, may involve an alteration in the activity of protein kinase C, cyclic AMP (cAMP)-dependent protein kinase or myosin light chain kinase by investigating the effects of MDL 27,032 on cyclic nucleotide phosphodiesterases (PDEs) and protein kinase activities. Strips of dog femoral artery or saphenous vein contracted with phorbol 12-myristate 13-acetate (PMA) were relaxed by 100 microM concentrations of MDL 27,032, as well as by other known inhibitors of PDEs [3-isobutyl-1-methylxanthine and papaverine], myosin light chain kinase (W-7) and protein kinase C (H-7 and polymyxin B). In contrast to 3-isobutyl-1-methylxanthine and papaverine, MDL 27,032 was either inactive or weak as an inhibitor of purified PDE types I, II, IVa and IVb. Similarly, it was a weak inhibitor of myosin light chain kinase. However, MDL 27,032 was a significantly more potent inhibitor of protein kinase C and cAMP-dependent protein kinase in cytosolic extracts of dog vein. Kinetic experiments utilizing purified rat brain protein kinase C revealed that inhibition with MDL 27,032 was competitive with Mg(++)-ATP (Ki 24 microM) and noncompetitive with phospholipid, diacylglycerol, PMA, calcium or substrate proteins. Inhibition of the catalytic subunit of cAMP-dependent protein kinase was also competitive with Mg(++)-ATP (Ki 14.3 microM). Similar results were obtained with MDL 27,032 and H-7 on both enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Tuberculosis epidemic among hospital personnel.

Six employees of the emergency department at Parkland Memorial Hospital developed active tuberculosis in 1983-1984. Five of the cases occurred four to 12 months after exposure to the index case, a patient with severe cavitary tuberculosis seen in the emergency department in April 1983. One resident physician developed cavitary disease after exposure to this patient. An additional employee case may have resulted from transmission from one of the initial employee cases. One immunocompromised patient may have acquired tuberculosis as a result of exposure to the index case. In addition, the tuberculin skin tests of at least 47 employees exposed to the index case converted from negative to positive. Of 112 previously tuberculin-negative emergency department employees who were tested in October 1983, 16 developed positive skin tests, including the 5 employees with active disease. Fifteen of these new positives had worked on April 7, 1983, while the index case was in the emergency department (X2 = 20.6, P less than 0.001). Factors related to the genesis of the epidemic included the disease characteristics in the index case and the recirculation of air in the emergency department. This investigation indicates that city-county hospital emergency department employees should be screened at least twice a year for evidence of tuberculosis and that the employee health services of such hospitals should regard the surveillance of tuberculosis infection among personnel at a high-priority level.

Aged↗
PubMed1988

Bacteriophage typing of Mycobacterium tuberculosis cultures from incidents of suspected laboratory cross-contamination.

Bacteriophage typing was performed on 235 Mycobacterium tuberculosis cultures submitted from 31 laboratories. In each instance, either the attending physician questioned the misdiagnosis of tuberculosis or the laboratory supervisor suspected that laboratory cross-contamination had occurred. Phage typing data confirmed these suspicions. Phage typing is a useful adjunct in the investigation of suspected cross-contamination of laboratory cultures of M. tuberculosis.

Bacteriophage Typing↗
PubMed1987

Expression of proteins of Mycobacterium tuberculosis in Escherichia coli and potential of recombinant genes and proteins for development of diagnostic reagents.

Recombinant plasmids containing DNA from Mycobacterium tuberculosis were transformed into Escherichia coli, and three colonies were selected by their reactivity with polyclonal antisera to M. tuberculosis. The three recombinant vectors contained DNA inserts of different sizes flanking a common 4.7-kilobase (kb) sequence. Each recombinant produced 35- and 53-kilodalton proteins (35K and 53K proteins, respectively) which were absent in the control E. coli. In Western blotting experiments, both proteins bound several antisera to M. tuberculosis but not antisera to other commonly isolated mycobacteria. Rabbits immunized with the recombinant 35K protein produced antisera which bound to both the 35K and 53K protein bands, a single 35K protein band present in a culture filtrate of M. tuberculosis, and single protein bands with differing molecular weights in whole-cell homogenates from other Mycobacterium spp. An additional recombinant vector containing a 2.2-kb subclone of the 4.7-kb sequence was constructed and, when used as a probe, demonstrated homology with various fragments of chromosomal digests of selected mycobacteria. Reactivity of this probe to Mycobacterium bovis and M. bovis BCG was indistinguishable from reactivity to M. tuberculosis. Immunoglobulin G reactivity to the 35K antigen was detected in antisera from 8 of 20 persons with active tuberculosis, 4 of 18 persons with leprosy, and none of 14 healthy controls. In contrast, reactivity to various proteins in M. tuberculosis culture filtrate was present in 18 of 20 patients with tuberculosis, 16 to 18 patients with leprosy, and 5 of 14 controls. The production of M. tuberculosis proteins by E. coli circumvents many difficulties encountered in the growth and manipulation of M. tuberculosis and may facilitate the development of better diagnostic and immunizing reagents.

Antibodies, Bacterial↗
PubMed1986

Restriction fragment analysis of chromosomal DNA defines different strains of Mycobacterium tuberculosis.

As an initial step in gaining a better understanding of the important clinical properties that vary between strains of mycobacteria, we attempted to find molecular markers that would define different strains of Mycobacterium tuberculosis. We used restriction fragment analysis with the endonuclease MboI and hybridization with total M. tuberculosis DNA to examine DNA differences between 15 strains of M. tuberculosis. We were able to identify different strains using this method. In order to assess the sensitivity of this method in identifying different strains, we compared it with phage typing. The 2 methods appear to be similar in sensitivity and also to be complementary. There were 2 examples where restriction fragment analysis did not separate strains with different phage types. In addition, there were 2 examples where phage typing did not separate strains with different restriction patterns. Finally, there were 2 epidemiologically unrelated strains with the same restriction pattern and the same phage type. This method of restriction fragment analysis of chromosomal DNA is potentially useful for epidemiologic studies of tuberculosis. Additionally, by analyzing the genome of M. tuberculosis, molecular markers may well be defined that will be useful in discovering the pathogenesis of the clinical properties of M. tuberculosis, which previously have been poorly understood.

DNA Restriction Enzymes↗
PubMed1984

The usefulness of phage typing Mycobacterium tuberculosis isolates.

Mycobacteriophage typing of Mycobacterium tuberculosis isolates was used as an epidemiologic aid in investigating the transmission of tuberculosis in community, industrial, and institutional outbreaks. The technique was also useful in other situations, e.g., documenting congenital transmission of infection and distinguishing exogenous reinfection from endogenous reactivation. Additional studies are indicated to further explore the value of phage typing for tracking the transmission of tuberculosis in the community.

Adolescent↗
PubMed1984

False-positive cultures of Mycobacterium tuberculosis.

During a single week in April 1982, cultures for Mycobacterium tuberculosis were reported positive from nine patients who did not appear clinically to have active infection. Each of the patients had only one positive culture out of multiple specimens cultured. At the time of investigation, five specimens were available and were found to be all of the same phage type which strongly suggested cross-contamination. Four patients received antituberculosis chemotherapy. In one year of follow-up of the five who did not receive chemotherapy, none developed clinical disease. The contamination was probably due to faulty laboratory technique, but the source of the contaminant is uncertain. This investigation suggests that patients without clinical evidence of active infection and with isolated positive cultures for Mycobacterium tuberculosis should be carefully evaluated before they are subjected to a prolonged, potentially toxic, and expensive course of chemotherapy.

Diagnostic Errors↗
PubMed1983

Phage-type patterns of Mycobacterium tuberculosis from Southeast Asian immigrants.

Cultures of Mycobacterium tuberculosis isolated from 86 Southeast Asian immigrants were phage typed as type 1 (10.5%), type 2 (57.0%), type 5 (23.2%), and type 8 (9.3%). Strains belonging to types 3, 4, 6, and 7 were not found among the 86 strains tested. The lytic patterns of 6 auxiliary phages further divided the strains into 5 to 14 additional subgroups. The phage-type distribution in the Asian cultures was different from the type distribution in cultures from residents in the United States.

Asia, Southeastern↗