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Biomedical subjects

M Roberts

Publications and source records attributed to M Roberts.

At least 199 records · Page 11Linked to original sources
PubMed1991

Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris.

A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05). Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.

Angina Pectoris↗
PubMed1991

Pertactin, an Arg-Gly-Asp-containing Bordetella pertussis surface protein that promotes adherence of mammalian cells.

A 69-kDa protein has been identified on the surface of the Gram-negative pathogen Bordetella pertussis that can elicit a protective immune response in animal models. This protein is associated with virulent strains of B. pertussis but its function has remained unclear. In this report we demonstrate that purified preparations of the 69-kDa outer membrane protein can promote the attachment of Chinese hamster ovary (CHO) cells. The interaction between the mammalian cells and this protein can be specifically inhibited by an Arg-Gly-Asp (RGD)-containing synthetic peptide that is homologous with a region found in the 69-kDa protein sequence. These studies indicate that a specific cell binding site containing an Arg-Gly-Asp sequence may be involved in the interaction of this bacterial protein with mammalian cell surfaces. To further investigate the role of this protein as a bacterial adhesin, a mutant of B. pertussis W28 that does not express the 69-kDa protein was constructed using the plasmid vector pRTP1. This mutant was 30-40% less efficient at adhering to CHO cells and to human HeLa cells than was the parent strain. These data support a role for this 69-kDa outer membrane protein in the attachment of B. pertussis to mammalian cells. We propose the name "pertactin" for this protein.

Amino Acid Sequence↗
PubMed1991

Identification and characterization of a protective immunodominant B cell epitope of pertactin (P.69) from Bordetella pertussis.

Epitopes defined by monoclonal antibodies (mAb) specific for the Bordetella pertussis outer membrane protein P.69 (pertactin) were mapped using a series of amino- and carboxy-terminal deletion mutants expressed in Escherichia coli. mAb were found to bind predominantly to a region of pertactin spanning a (Pro-Gln-Pro)5 repeat motif and one mAb was found to bind to another region spanning a (Gly-Gly-Xaa-Xaa-Pro)5 repeat motif. To localize further the mAb-binding sites, a panel of synthetic peptides, a series of 94 overlapping hexameric peptides, and a P.69 30-amino acid fusion to a hepatitis B core protein (HBcAg-69), were synthesized. This combined approach has identified the binding site for the mAb BBO5: Pro-Gly-Pro-Gln-Pro-Pro; mAb BBO7, E4A8 and E4D7: Ala-Pro-Gln-Pro-Pro-Ala-Gly-Arg; and mAb BPE3: Thr-Leu-Trp-Tyr-Ala-Glu-Ser-Asn-Ala-Leu-Ser-Lys-Arg. We have used a non-lethal murine respiratory model of B. pertussis infection to investigate the ability of a peptide containing the epitope of the mAb BBO5 to elicit protective immunity. Immunization of mice with the HBcAg-69 protein prevented growth of B. pertussis in the lungs compared to mice receiving HBcAg alone, and protection correlated with high titers of anti-P.69 antibodies.

Amino Acid Sequence↗
PubMed1991

The parasites of the Polynesian rat within and beyond New Zealand.

A list of the ecto- and endoparasites of the Polynesian rat, Rattus exulans, from throughout its geographical range is presented here. The majority of the New Zealand populations included in this survey came from 'exulans only' islands while all but one of the non-New Zealand reports came from places where other rodent species are sympatric. This information is intended among other things to highlight gaps in our knowledge of and stimulate an interest in the parasitology of this rat.

Animals↗
PubMed1991

The parasites of the Polynesian rat: biogeography and origins of the New Zealand parasite fauna.

Unique aspects of the prehistory and current distribution of the Polynesian rat (Rattus exulans Peale) have been applied to the problem of determining the biogeographical origin of its parasites as found on 'exulans only' islands of New Zealand. The database consists of collated records of both endo- and ectoparasites reported from throughout this rat's geographical range. The analytical method is based on the concepts of Sprent (1969. Immunity to Parasitic Animals, pp. 14-17) and includes the formulation and testing of two hypotheses. A total of six 'heirloom' species is identified, and a further seven are classified as 'old souvenirs'. Contrary to prediction, 11 species are considered to be 'new souvenirs', acquired from other rodent species now present in New Zealand.

Animals↗
PubMed1991

A comparison of cutaneous testing and ELISA testing for assessing reactivity to ethylene oxide-human serum albumin in hemodialysis patients with anaphylactic reactions.

In five patients who have experienced anaphylaxis and in 29 patients who have not had such episodes during hemodialysis, we have performed two immunologic studies: cutaneous testing with ethylene oxide-human serum albumin (ETO-HSA) and ELISA for IgE against ETO-HSA. Four of five patients with reactions had positive cutaneous tests, whereas only one nonreactor had a positive skin test (p less than 0.0002). The same four of five patients with reactions also had positive ELISA results, whereas three nonreactors has positive ELISA results (p less than 0.003). In this group of patients, the positive predictive value of cutaneous testing (80%) is somewhat higher than that of ELISA testing (57%). However, the sensitivity, specificity, and negative predictive values are similar. We conclude that cutaneous testing with ETO-HSA probably offers a small advantage over IgE against ETO-HSA as determined by ELISA.

Anaphylaxis↗
PubMed1991

Hypogammaglobulinemia associated with cytomegalovirus pneumonia.

Transient but profound hypogammaglobulinemia occurred during cytomegalovirus (CMV) pneumonia in a patient who developed striking declines in number of T lymphocytes. A 66-year-old, female, human immunodeficiency virus-negative patient requiring long-term hemodialysis had normal serum immunoglobulin concentrations before the onset of CMV pneumonia (IgG, 1070-1470 mg/dl; IgA, 94-102 mg/dl; IgM, 30-48 mg/dl). During the pneumonia episode, serum immunoglobulin concentrations were profoundly reduced (IgG, 440 mg/dl; IgA, 40 mg/dl; IgM, 25 mg/dl). Total lymphocytes declined from 3048/mm3 to 212/mm3 with reductions in CD4+CD45- lymphocytes (inducers of B cells) to 9% (nl, 24%-32%) and CD4+CD45+ lymphocytes (inducers of suppressor T cells) to 4% (nl, 14%-22%). CD8 lymphocytes were reduced to 5% (nl, 19%-31%). As the pneumonia resolved, serum immunoglobulin concentrations returned to normal. This is one of the few reported instances of CMV infection apparently causing hypogammaglobulinemia.

Agammaglobulinemia↗
PubMed1991

Prevention of spinal cord injury: an elementary education approach.

Spinal cord injury (SCI) results in permanent paralysis and most often happens to teenagers and young adults. High risk behaviors are most often the cause; therefore these injuries are often preventable. In response to a gap in existing prevention programs, an elementary age SCI prevention program was developed, designed for implementation by teachers. Evaluation was carried out via a quasi-experimental pre-post comparison group design. Experimental students demonstrated significantly improved knowledge of SCI and its prevention. Similar changes in self-reported safety belt use were not noted. Development of the curriculum, related grant activities, and plans for national dissemination are described.

Child↗
PubMed1991

Intranasal immunization using the B subunit of the Escherichia coli heat-labile toxin fused to an epitope of the Bordetella pertussis P.69 antigen.

The plasmid pBRD026, which directs expression of the B subunit of the Escherichia coli heat-labile toxin (LTB), was modified so that DNA encoding epitopes could be inserted at the 3' end of the gene. An oligonucleotide linker containing restriction sites for BglII and SpeI was inserted at the SpeI site at the 3' end of the LTB gene to form plasmid pFV1. This linker also encodes the amino acid sequence Gly-Pro-Gly-Pro which we propose acts as a 'hinge' between the LTB and the foreign epitope. Oligonucleotides specifying an epitope from the Bordetella pertussis P.69 outer membrane protein were cloned into pFV1 to form pFV169. The resultant fusion protein (LTB69) was partially purified from the periplasm of E. coli strains in a soluble pentameric form which could bind GM1 gangliosides. Mice immunized intranasally with purified LTB69 produced antibodies against both LTB and the P.69 protein. In addition, ELISPOT assays demonstrated the presence of LTB-specific and P.69-specific antibody-secreting cells in the lungs of immunized mice.

Administration, Intranasal↗
PubMed1991

Construction and characterization of Bordetella pertussis mutants lacking the vir-regulated P.69 outer membrane protein.

The Bordetella pertussis P.69 protein is an immunogen with vaccine potential. The role of this protein in pathogenesis is unclear; it has been associated with the toxic adenylate cyclase and adhesion to eukaryotic cells. For further analysis of the role of P.69 in the biology of B. pertussis, we have constructed strains which specifically lack P.69. The cloned P.69 (prn) gene of B. pertussis was insertionally inactivated with a kanamycin-resistance cassette. This inactivated gene was used to construct P.69- mutants of B. pertussis by allelic exchange using plasmid pRTP1. B. pertussis P.69- strains produced normal levels of other vir-regulated factors, including adenylate cyclase. The serotype of B. pertussis, determined by Eldering and Preston typing sera and monoclonal antibodies, was also unaffected by the presence or absence of P.69. The ability of a prn mutant to adhere to and invade HEp2 cells was not significantly different from that of its parent strain. A strain containing a mutation in fhaB was significantly less adhesive and invasive than its parent, and a prn fhaB double mutant exhibited an even greater reduction in adhesiveness and invasiveness down to levels comparable with a Vir- strain. However, strains harbouring mutations in FHA and/or P.69 were able to colonize or multiply in the murine respiratory tract, although a Vir- strain was unable to survive and proliferate in the same infection model.

Adenylyl Cyclases↗
PubMed1991

Comparison of basal and prandial insulin therapy in patients with secondary failure of sulphonylurea therapy.

A group of 35 normal weight patients with secondary failure of sulphonylurea therapy (fasting plasma glucose greater than 8.0 mmol l-1 on maximal dose of sulphonylurea) were randomly assigned to receive either a single injection of a basal insulin supplement (human ultralente insulin, n = 16) or three or four injections of a preprandial insulin supplement (human unmodified insulin, n = 19). Patients performed self-monitoring of capillary blood glucose and adjusted their insulin doses in an effort to achieve fasting and preprandial capillary glucose concentrations of less than 7.0 mmol l-1. Blood glucose control after 16 weeks of insulin therapy was improved to a similar extent by both regimens (HbA1 basal insulin group 12.5 +/- 1.2 (+/- SD) falling to 10.7 +/- 2.2%; preprandial group 12.0 +/- 1.6 falling to 9.5 +/- 1.6%). Preprandial insulin gave better control of daytime blood glucose levels but fasting plasma glucose did not differ between the two regimens (basal group 10.6 +/- 3.6, preprandial group 11.1 +/- 3.6 mmol l-1). Insulin dose was greater in the preprandial group (44.1 +/- 17.9 U day-1) than in the basal group (26.7 +/- 12.5 U day-1 (p less than 0.005), but there was no difference in the frequency or severity of hypoglycaemia between the two treatments. Only the preprandial therapy group showed significant weight gain (2.7 +/- 3.0 kg). While both regimens led to improvement of blood glucose control, these results suggest that neither basal nor preprandial insulin alone can achieve ideal blood glucose control through 24 h in patients with fairly severe failure of control on sulphonylurea therapy.

Blood Glucose↗
PubMed1991

The topoisomerase I inhibitor, camptothecin, inhibits equine infectious anemia virus replication in chronically infected CF2Th cells.

Camptothecin (CPT), a topoisomerase I-specific inhibitor, was found in this study to inhibit the replication of equine infectious anemia virus (EIAV) in chronically infected CF2Th cells (designated CF2Th/EIAV). By measuring viral reverse transcriptase activity in the culture medium, we demonstrated that treatment for 1 h with noncytotoxic doses of this drug inhibited production by 32 to 52%, whereas continuous exposure to this drug resulted in an 85 to 92% inhibition. No effect on the viability or growth rate of the cells was detected in any of these treatments. Indirect immunofluorescence analysis of the CPT-treated CF2Th/EIAV cells with anti-p26 capsid protein antibodies showed 60 to 85% reduction in the immunofluorescence-positive cells following drug treatment, and radioimmunoprecipitation analysis of these cells showed a comparable decrease of the pr55gag precursor protein. These data suggest that CPT acts as an anti-EIAV agent to block virus replication in the chronically infected cells.

Animals↗
PubMed1991

One flag, many worlds. Health issues at the border.

The U.S.-Mexican border divides two countries with widely differing priorities and expectations--and inseparable health, environmental, economic and cultural concerns. One half of this 2,000-mile border is in Texas. HealthTexas looks at border health, as typified by communities at either end of the state. Later this year, HealthTexas will examine how Texas hospitals market to Mexico.

Child↗
PubMed1991

Blue skies, sunny days.

The storm clouds and bad news surrounding rural hospitals sometimes block out the other side of the story. In this issue, HealthTexas looks at three rural health care providers--Medina Community Hospital, Starr County Memorial Hospital, and Moore County Hospital District--that are doing far more than just hanging on; they are succeeding. What they share is important and instructive: a strong commitment to their communities, a whatever-it-takes-to-get-the-job-done attitude, and a creative approach to defining the role of rural health care providers.

Community-Institutional Relations↗
PubMed1991

Stimulation of sodium transport by duramycin in cultured human colonic epithelia.

Effects of two peptide antibiotics, duramycin and Ro 09-0198, on ion transport in cultured human colonic epithelia were investigated. Both peptides acted on the apical face of epithelial monolayers, causing an increase in ion transport measured as short circuit current. Concentration-response relationships were complex, because above a concentration of 2 to 5 microM, the peptides caused currents either to decline toward zero or become large and unstable. Ion substitution experiments showed that the majority of the current response was due to electrogenic sodium absorption. An outward chloride current could also be induced by duramycin, provided an outwardly directed chloride gradient was imposed. It was also shown that the peptides could increase [Ca]i, probably by creating entry sites in the apical face. Duramycin was also able to create large conductance (2000 pS) channels in "black" lipid bilayers. It is proposed that the antibiotics interact with membrane lipids in the apical faces of colonic epithelia to create artificial nonspecific ion channels. The prevailing electrochemical gradients which exist when the epithelia are bathed symmetrically in Krebs-Henseleit solution result in increased electrogenic sodium transport. No evidence was found for colonic epithelia that duramycin or Ro 09-0198 interacted specifically with either membrane channels or receptors to increase ion transport.

Amino Acid Sequence↗