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Biomedical subjects

B Hill

Publications and source records attributed to B Hill.

At least 55 records · Page 3Linked to original sources
PubMed1997

Delineation of the human hematolymphoid system: potential applications of defined cell populations in cellular therapy.

Hematopoietic stem cells (HSC) have the capacity to reconstitute all the blood cells in the body. HSC are rare, representing on average 0.05% of the mononuclear cells present in healthy human bone marrow. Due to their capacity for self-renewal and their pluripotent, long-term reconstituting potential, HSC are considered ideal for transplantation to reconstitute the hematopoietic system after treatment for various hematologic disorders or as a target for the delivery of therapeutic genes. Human HSC also have potential applications in restoring the immune system in autoimmune diseases and in the induction of tolerance for allogeneic solid organ transplantation. With the increased interest in human HSC for clinical applications, technology for the isolation of candidate HSC and knowledge of human hematopoiesis have been growing rapidly. In this article, we discuss the functional characterization of a human CD34+Thy-1+ HSC population which is essentially free of residual disease, our efforts to generate alternate monoclonal antibodies for the isolation of clinically useful stem or progenitor cell populations, and the identification of a novel lymphoid progenitor as part of an exploration towards defining progenitors with potential application as adjuncts to HSC-based cellular therapy.

Adoptive Transfer↗
PubMed1997

Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia.

Nine isolates of Escherichia coli were recovered from seven blood cultures over a period of 3 months from a 19-month-old female with aplastic anemia. Initial isolates were susceptible to extended-spectrum cephalosporins, including ceftazidime (MIC, < or = 0.25 microgram/ml), but gradually became resistant to this drug (MICs, > or = 128 micrograms/ml) and other cephalosporins and the monobactam aztreonam. Molecular typing methods, including plasmid profile analysis, pulsed-field gel electrophoresis, and arbitrarily primed PCR, indicated that the nine isolates were derived from a common ancestor. Dot blot hybridization and PCR analysis of total bacterial DNA using blaSHV- and blaTEM-specific DNA probes and primers identified the presence of a blaTEM beta-lactamase gene in all of the isolates and a blaSHV gene in the isolates with elevated ceftazidime MICs. Isoelectric focusing analysis of crude lysates showed that all nine isolates contained an enzyme with a pI of 5.4 corresponding to the TEM-1 beta-lactamase, and those isolates containing an SHV-type beta-lactamase demonstrated an additional band with a pI of 7.6. The first of the ceftazidime-resistant isolates appeared to hyperproduce the SHV enzyme compared to the other resistant isolates. DNA sequencing revealed a blaSHV-1 gene in the first ceftazidime-resistant isolate and a novel blaSHV gene, blaSHV-8, with an Asp-to-Asn substitution at amino acid position 179 in the remaining four isolates. Three of the ceftazidime-resistant isolates also showed a change in porin profile. The patient had received multiple courses of antimicrobial agents during her illness, including multiple courses of ceftazidime. This collection of blood isolates from the same patient appears to represent the in vivo evolution of resistance under selective pressure of treatment with various cephalosporins.

Amino Acid Sequence↗
PubMed1997

Effects of hibernation on neural and endothelial control of mesenteric arteries of the golden hamster.

The effects of hibernation on mesenteric arterial innervation and function were examined using pharmacological and immunohistochemical techniques in age-matched controls, cold-exposed controls, and 4-wk-hibernated golden hamsters. Electrical field stimulation of the isolated mesenteric arterial bed elicited frequency-dependent vasoconstriction. The sensitivity of responses was significantly increased in tissues from hibernating animals compared with cold-exposed controls. Vasoconstrictor responses to exogenous norepinephrine were also increased in hibernation. However, there was a significant decrease in sensitivity of vasoconstriction to ATP in hibernated and cold-exposed tissue compared with age-matched controls. In preparations preconstricted with methoxamine, endothelium-dependent vasodilator responses to acetylcholine and ATP were similar among the groups. Immunohistochemical investigation of mesenteric arteries revealed no differences among the groups in density of innervation by nerves immunoreactive for tyrosine hydroxylase, neuropeptide Y, and calcitonin gene-related peptide. Postjunctional changes appear to occur in hibernation, leading to augmentation of sympathetic vasoconstriction, which is consistent with the increase in peripheral vascular resistance in hibernation. Endothelium-dependent vasodilatation is not significantly changed in hibernation in the hamster mesenteric arterial bed.

Acetylcholine↗
PubMed1997

Notes on the training of workers in the health sector.

The following notes attempt to contribute to questions on planning, design, and evaluation of training courses for technical personnel in the health sector. The authors analyze and compare trainees' views on their courses and point out issues related to planning, implementation, and some benefits of training for trainees' lives.

Journal Article↗
PubMed1997

Reduction in blood culture contamination rate by feedback to phlebotomists.

OBJECTIVE: To determine whether monitoring and feedback of blood culture contamination rates to phlebotomists would reduce the overall contamination rate. DESIGN: Before and after interventional study. SETTING: Blood cultures collected by venipuncture by phlebotomists at Foothills Hospital, Calgary, a tertiary care teaching hospital. INTERVENTION: Feedback of contamination rates calculated from a laboratory definition of blood culture contamination. The definition was based on isolation of typical skin organisms from a single blood sample when two samples were obtained. MAIN OUTCOME MEASURE: Reduction in the laboratory-defined contamination rate in the second year. RESULTS: Of 8462 cultures collected by phlebotomists in the prefeedback year, 224 (2.6%) were contaminated, compared to 131 (1.4%) of 9282 cultures in the postfeedback year. There was a rise in the total number of positive cultures regarded as significant but a fall in the number of coagulase-negative staphylococci that were regarded as significant by our definition. The rate of contamination in blood cultures collected by nonphlebotomists did not change. CONCLUSIONS: The contamination rate decreased after feedback. Our definition of contamination was imperfect and could be improved, but it was valuable in achieving a real reduction in blood culture contamination.

Bacteria↗
PubMed1997

[Inhibitors of Ras farnesylation: tomorrow's anticancer agents?].

Increasing evidence implicates a critical role for aberrant Ras function in promoting the development of human tumours and has provided the impetus for identifying anti-Ras drugs for therapy. In order to be active the protooncogene ras must be associated with the plasma membrane. This feature depends crucially upon its farnesylation (addition of a 15 carbon moiety) by the enzyme farnesyl protein transferase. In the search for new anticancer strategies and agents, potent and selective inhibitors of this enzyme have been designed. The more recent of these compounds have produced impressive results in vivo against human tumours xenografted onto nude mice, without notable toxicity, making them promising candidates for clinical evaluation.

Alkyl and Aryl Transferases↗
PubMed1996

Innervation and nitric oxide modulation of mesenteric arteries of the golden hamster.

Immunohistochemical and pharmacological techniques were used to examine perivascular nerves, endothelium and the effects of inhibition of nitric oxide synthesis on responses in mesenteric arteries/perfused mesenteric arterial beds of the Golden hamster. Frequency-dependent vasoconstrictions to electrical field stimulation and dose-dependent vasoconstrictions to noradrenaline were significantly augmented by NG-nitro-L-arginine methyl ester (10(-5) M), an inhibitor of nitric oxide synthase. In preparations with tone raised with methoxamine (10 microM) dose-dependent relaxations to ATP, but not to acetylcholine, were blocked by NG-nitro-L-arginine methyl ester. In the presence of guanethidine (5 microM) to block sympathetic neurotransmission there was no neurogenic relaxation to electrical field stimulation. Furthermore, the sensory neurotoxin capsaicin (0.05-5 nmol) did not elicit relaxation. Immunohistochemical studies demonstrated dense plexuses of fibres immunoreactive for tyrosine hydroxylase and neuropeptide Y, a plexus of moderate density for calcitionin gene-related peptide and an absence of fibres immunoreactive for substance P and vasoactive intestinal polypeptide. Of particular interest is the finding that whereas sympathetic perivascular nerves and nitric oxide regulate the function of hamster mesenteric arteries, there is no apparent motor function of calcitonin gene-related peptide-containing sensory nerves.

Animals↗
PubMed1996

The human factor.

Defining the core activity of psychiatric nursing is helpful if the discipline seeks professionalization. A definition offers a sense of stability within the current culture of change in care provision. However, core activity may be incongruent with postmodern ideas and practice. The paper attempts to square this circle. It addresses the complexity of describing core activity when this is based on implicit knowledge of practice, based in art rather than science. Using a phenomenological research approach, the research involved encouraging psychiatric nurses within residential schemes to consider the meaning of their concrete activity. Initial findings suggest that the core activity is working with extraordinary people within 'ordinary' relationships, and in 'ordinary' contexts.

Attitude of Health Personnel↗
PubMed1996

Regulation of polyamine synthesis and transport by fibroblast growth factor in aortic smooth muscle cells.

Basic-FGF (FGF2) is implicated as a regulator of smooth muscle cell proliferation that develops after arterial injury. Polyamines are essential for cell growth and differentiation and may mediate some of the FGF2-elicited responses. To examine this possibility, the effect of FGF2 on polyamine synthesis and uptake was tested on rat arterial smooth muscle cells. Exposure of cells to FGF2 for 24 and 48 h resulted in increased intracellular polyamine content. Ornithine decarboxylase (ODC) activity increased in FGF2-treated cells after 6 h of treatment, whereas no increases were detected in ODC mRNA steady-state levels. Basic-FGF increased maximal polyamine transport rate without changes in Km. Treatment with actinomycin D decreased polyamine transport. The effect of cyclohexamide on polyamine uptake was dose dependent. These studies indicate that treatment of vascular smooth muscle cells with FGF2 results in increases in intracellular polyamine content, polyamine synthetic activity, and polyamine transport.

Animals↗
PubMed1996

Rebuilding the face of George Buchanan (1506-1582).

For many years, controversy has existed as to which of several portraits bore the closest resemblance to George Buchanan, Scottish humanist, historian, churchman, statesman and tutor to James VI of Scotland (later James I of England). It was considered that a formal facial reconstruction from his skull, which is housed in Edinburgh University Anatomy Museum, would help clarify this long standing dilemma. The reconstruction process and its results are described and illustrated.

Famous Persons↗
PubMed1996

High-level expression of a novel epitope of CD59 identifies a subset of CD34+ bone marrow cells highly enriched for pluripotent stem cells.

To further define the hierarchy of human hematopoietic progenitor cells, we have attempted to identify antibodies to cell-surface molecules expressed on CD34+ progenitor cell subsets. Herein we describe the utility of a new monoclonal antibody, HCC-1, which binds to a novel epitope of CD59 differentially expressed among CD34+ progenitor cells. HCC-1 subdivides the adult marrow CD34+ population into HCC-1high and HCC-1low/- fractions of approximately equal size. Cobblestone area-forming cells (CAFC) in long-term bone marrow culture were enriched 10-30-fold in CD34+HCC-1high cells compared with CD34+HCC1-low/- cells and two-fold compared with CD34+ cells. When injected into fetal human bone fragments implanted in SCID mice, the CD34+HCC-1high population showed potent engrafting activity leading to the production of myeloid, lymphoid, and erythroid elements, as well as the retention of progenitor cell phenotype. These studies demonstrate that the CD34+HCC-1high population contains primitive pluripotent hematopoietic stem cells. No hematopoietic engrafting activity was detected in the CD34+HCC-1low/- population. Consistent with this finding, simultaneous five-color flow cytometric analysis revealed that HCC-1high cells include virtually all CD34+Thy-1+Lin- cells, a cell population previously characterized as highly enriched for primitive pluripotent hematopoietic stem cells. The ability of CD34+ cells divided into subsets by HCC-1 to produce T cells was assessed by transplantation of sorted cells into human fetal thymus implanted into SCID mice. A higher frequency of thymus-engrafting activity was observed in the CD34+HCC-1high than in the CD34+HCC-1low/- population. Consistent with the limited ability to engraft in the SCID-hu thymus model, the CD34+HCC-1low/- population was shown to contain a low frequency of CD34+CD10+ lymphoid progenitor cells. We conclude that the HCC-1 epitope is expressed at high levels on a subset of CD34+ cells that contain virtually all primitive pluripotent hematopoietic stem cells and that the population of CD59 molecules expressed on CD34+ cells is not homogeneous.

Animals↗
PubMed1996

Respiratory symptoms and respiratory function in workers exposed to tea fluff.

A questionnaire survey of respiratory symptoms was carried out on a group of subjects with exposure to tea fluff in a packaging plant and compared with a group of unexposed workers. The subjects had a higher prevalence of rhinitis, bouts of coughing and chest tightness than the controls. Except in the case of rhinitis however, the differences disappeared when allowance was made for either hay fever or smoking. From the original group of subjects, two smaller groups were chosen, one with and one without symptoms, and peak expiratory flow rates were measured over a 12-day period, including eight working and four non-working days. The mean difference in peak flow was greater on the non-working than on the working days and was not related to age, sex, years of exposure, smoking or atopy. We conclude that there is little evidence to suggest that this group of tea packers shows signs of sensitization but that they are probably exposed to an irritant in the tea fluff.

Adult↗
PubMed1995

Molecular cloning of a novel myeloid granule protein.

Granulocytes are recognized by the presence of granules, including primary (azurophilic) and secondary types. Each granule type contains distinct and characteristic families of enzymes. We have screened a murine bone marrow cDNA library to obtain a series of sequences corresponding to mRNAs which are both myeloid-specific and appear to be expressed only in immature bone marrow cells. A 1,160 bp sequence (B9) has been isolated, which shows restricted expression in murine bone marrow, with the highest levels in cultures enriched for promyelocytes. Translation yields a single open reading frame of 167 amino acids and a calculated MW of 19.33 kd. A single potential N-glycosylation site is present. Evaluation of the amino terminal sequence shows 2 polar amino acids flanking a hydrophobic region, suggesting a signal sequence and the possibility of post-translational modification. An extensive search of the protein data base reveals 30% identity over 90 amino acids with porcine cathelin, a cystatin-like cysteine proteinase inhibitor. This sequence identity includes conservation of the 4 cysteine residues noted in all members of the cystatin superfamily. In an attempt to further characterize this novel sequence, a polyclonal antiserum was prepared by immunization with a 20 amino acid synthetic peptide corresponding to a unique portion of the carboxy terminus. Immunoelectron microscopy localized B9 to neutrophilic granules. We have identified a novel myeloid-specific granule protein related to porcine cathelin, but showing important structural differences. This may represent the first isolated member of a new cystatin family. More importantly, the small size of the B9 gene and its tight pattern of early expression make B9 an excellent reporter molecule for the study of new factors important in myeloid differentiation.

Amino Acid Sequence↗
PubMed1995

Multiple antimicrobial resistance of pneumococci in children with otitis media, bacteremia, and meningitis in Slovakia.

Penicillin-resistant pneumococci have been isolated from middle ear fluid, blood, cerebrospinal fluid, and nasopharyngeal secretions of several hundred children in Slovakia since 1985; 116 of these isolates were serotyped and tested for susceptibility to antimicrobial drugs at the Centers for Disease Control and Prevention. To define the prevalence of drug-resistant pneumococci and identify risk factors for infection, laboratory and medical records were reviewed. Nearly all (96%) of the resistant strains tested were serotype 14. Of these, all were resistant to penicillin (MIC, 4-16 micrograms/mL); most were resistant to cefaclor, erythromycin, tetracycline, and chloramphenicol; and many had decreased susceptibility to trimethoprim-sulfamethoxazole and ceftriaxone. Frequent antibiotic use, prior hospitalization, and length of hospital stay (P < .001 for all 3) were associated with infection with resistant strains. These findings suggest the need for routine screening of pneumococcal isolates for penicillin resistance and highlight the importance of controlling globally the spread of resistant pneumococci.

Bacteremia↗