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Biomedical subjects

M Duncan

Publications and source records attributed to M Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome V.

Here we report the sequence of 569,202 base pairs of Saccharomyces cerevisiae chromosome V. Analysis of the sequence revealed a centromere, two telomeres and 271 open reading frames (ORFs) plus 13 tRNAs and four small nuclear RNAs. There are two Tyl transposable elements, each of which contains an ORF (included in the count of 271). Of the ORFs, 78 (29%) are new, 81 (30%) have potential homologues in the public databases, and 112 (41%) are previously characterized yeast genes.

Base Sequence↗
PubMed1997

Multiple colonization defects in a cysteine protease mutant of Porphyromonas gingivalis.

A cysteine protease mutant, G-102, of Porphyromonas gingivalis 381 defective in the rgp-1 gene has been recently constructed in this laboratory. In order to evaluate the role of the protease in the virulence properties of P. gingivalis, a number of putative periodontopathic properties of the mutant were evaluated. Relative to the parental strain, mutant G-102 was demonstrated to be defective in interacting with Gram-positive bacteria as well as cultured epithelial cells. In addition, the mutant was altered in attaching to the protein components of extracellular matrix as well as to type I collagen. Some of these alterations could result from the decreased autoaggregation displayed by mutant G-102 relative to strain 381. However, since the epithelial cell attachment assays were carried out at very low bacterial densities, it is unlikely that reduced autoaggregation of the mutant is responsible for its decreased ability to attach to these eucaryotic cells. Electron microscopic examination of the cells also revealed that mutant G-102 was altered in normal fimbrae expression. In addition, reduced expression of the 43 kDa fimbrial subunit in the mutant was detected with both Western and Northern blotting. These results indicated that the rgp-1 gene product can play either a direct or indirect role in the colonization properties of P. gingivalis.

Adhesins, Bacterial↗
PubMed1996

Unusual complications of cervical spine surgery for cervical myelopathy in rheumatoid arthritis.

Cervical myelopathy is a recognized complication of rheumatoid arthritis and other inflammatory arthropathies. In a significant proportion of patients, surgical stabilization of the cervical spine offers the best opportunity for improvement of symptoms and long-term survival. We report two cases that illustrate some potential complications of cervical spine surgery and which also emphasize the need for vigilance when caring for patients in this group.

Arthritis, Rheumatoid↗
PubMed1996

Role of Porphyromonas gingivalis protease activity in colonization of oral surfaces.

Cysteine proteases, including Arg-gingipain of Porphyromonas gingivalis, have been implicated as important virulence factors in periodontal diseases. These enzymes are also involved in the hemagglutinating activity of the organisms. In order to determine the role of proteases in the colonization of the gingival margin, we have compared the attachment properties of P. gingivalis 381 with those of its Arg-gingipain-defective mutant, G-102. Interactions with gram-positive bacteria, human oral epithelial cells, extracellular matrix proteins, and type I collagen were evaluated. In all cases, mutant G-102 was deficient in attachment relative to the parental strain. The mutant's defects could be explained, in part, by the weak autoaggregation displayed by the mutant, which appeared to result from altered fimbrial expression. Both Western blot (immunoblot) and Northern (RNA) blot analyses indicated reduced expression of the major 43-kDa fimbrillin subunit in the mutant. These results suggest that Arg-gingipain may play both direct and indirect roles in the colonization of the gingival margin. In addition, fimbriae may play a direct role in interacting with some host surfaces.

Bacterial Adhesion↗
PubMed1995

Cross-species identification of proteins separated by two-dimensional gel electrophoresis using matrix-assisted laser desorption ionisation/time-of-flight mass spectrometry and amino acid composition.

Amino acid analysis and matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry were used to identify nine of twelve proteins originally separated by two-dimensional electrophoresis and derived from an organism poorly defined at the molecular level (Spiroplasma melliferum). Two of three unidentified proteins appeared to be novel. The percentage amino acid composition and the molecular mass of peptide fragments generated by tryptic digestion were used to search the PIR/SWISS-PROT and MOWSE databases respectively. Lists of candidate proteins were independently generated and ranked from data obtained by both methods. A putative identification was allocated when a single candidate protein appeared in both lists of computer-generated rankings. Results were verified using N-terminal protein microsequencing. The combined use of amino acid composition and MALDI-TOF mass spectrometry allowed a high degree of confidence to be placed in such identifications because they were based upon homologous data sets of at least 20 parameters (16 amino acids and 4-10 tryptic digest fragments). A further two parameters, estimated M(r) and, to a lesser extent, pI, were also used to reinforce this measure of confidence. Ranking of candidate proteins by one method alone could lead to false identification. Both techniques can process large numbers of samples rapidly. In light of the increasing number of entries in both gene and protein databases, this approach is likely to become an essential first step for the characterisation of proteins, particularly across species boundaries.

Amino Acid Sequence↗
PubMed1995

Hypopi (Acari: Hypoderatidae) from subcutaneous tissues of the African spoonbill (Aves: Ciconiiformes: Threskiornithidae).

Two new species and a new host record for two additional species of deutonymphs of the family Hypoderatidae are described from subcutaneous adipose tissues of a captive African spoonbill, Platalea alba Scopali. Phalacrodectes (Phalacrodectes) platalea Pence & Duncan, n. sp. most closely resembles P. (P.) whartoni Fain and P. (P.) pelecani Pence & Courtney in chaetotaxy and cuticular sclerotization, but it differs by having secondary perigenital sclerotization surrounding the genital openings and parallel genital papillae. P. (P.) schoutedeni Fain is reexamined for the first time since its original description, which was based on a single specimen from a cormorant; we believe the affinity of this species is closer to those infecting ibises and spoonbills and that the former record was a case of accidental host capture among birds sharing the same rookery. A new host record is established for Neottialges platalea Fain & Laurence from the African spoonbill. The heavy idiosomal sclerotization, incomplete genital apodeme, and long dorsal setae differentiate Neottialges intermedius Pence & Duncan, n. sp. from all other species in the genus. Because this suite of characters was previously used to separate the three subgenera of the genus Neottialges, we propose that Neottialges, Caloenectes, and Pelecanectes should now be considered invalid subgeneric taxa.

Animals↗
PubMed1994

Evidence that L-(+)-lactate dehydrogenase deficiency is lethal in Streptococcus mutans.

In order to construct an effector strain for the replacement therapy of dental caries, we wished to combine the properties of low-level acid production and high-level colonization potential in a strain of Streptococcus mutans. To this end, we made a deletion in the lactate dehydrogenase (LDH) gene cloned from the bacteriocin-producing S. mutans strain JH1000. However, we were unable to substitute the mutant for the wild-type allele by transformation with linear DNA fragments. The mutated gene, carried on a suicide vector, was shown by Southern analysis to integrate into the JH1000 chromosome to yield transformants carrying both the wild-type gene and mutated LDH gene. Three spontaneous self-recombinants of one heterodiploid strain were isolated by screening 1,500 colonies for a loss of the tetracycline resistance encoded by the gene used to mark the LDH deletion. In all three cases, Southern analysis showed that a loss of tetracycline resistance was accompanied by a loss of the mutated LDH gene, resulting in restoration of the wild-type genotype. However, screening the same number of colonies for self-recombinants that did not make lactic acid during anaerobic growth in Todd-Hewitt broth failed to identify clones in which the wild-type allele was lost. A second, simpler screening of more than 80,000 colonies grown aerobically on glucose tetrazolium medium to identify low-level-acid-producing colonies was also unsuccessful. These results are interpreted as indicating that LDH deficiency is lethal in S. mutans under the cultivation conditions used in these experiments. The physiological bases for this hypothesis are described.

Blotting, Southern↗
PubMed1994

L-(+)-lactate dehydrogenase deficiency is lethal in Streptococcus mutans.

The previously cloned gene for L-(+)-lactate dehydrogenase (LDH) from Streptococcus mutans was mutagenized in vitro. An Escherichia coli transformant which expressed a thermolabile LDH activity was identified. The ldh(Ts) gene was introduced into S. mutans on a suicide vector to create a heterodiploid expressing both wild-type and thermolabile LDH activities. Self-recombinants which had only one ldh gene were isolated. One of these clones expressed only the thermolabile LDH activity. This isolate grew well at 30 degrees C but did not grow at 42 degrees C under a variety of cultivation conditions, thereby proving that LDH deficiency is lethal in S. mutans in the absence of compensatory mutations.

Blotting, Southern↗
PubMed1994

Arsenic intoxication presenting with macrocytosis and peripheral neuropathy, without anemia.

A case of arsenic intoxication associated with macrocytosis and neuropathy, without anemia, is presented. Evaluation of a 68-year-old man with a long history of peripheral neuropathy and persistent macrocytosis revealed exposure to an insecticide. Analysis of urine and hair revealed elevated levels of arsenic. A short course of d-penicillamine failed to promote urinary excretion of arsenic. Removal of the insecticide resulted in resolution of macrocytosis and slight improvement of neuropathy. This case emphasizes that arsenic intoxication should be considered in patients with macrocytosis with peripheral neuropathy, even in the absence of anemia.

Aged↗
PubMed1993

Germ cell deficient (gcd) mouse as a model of premature ovarian failure.

Premature ovarian failure (POF) in women is characterized as menopause commencing before age 35. Although some cases of POF appear to be inherited, no experimental animal models of familial POF are available. Recently a mouse mutation has been identified that results in infertility due to a lack of primordial germ cells arising in early embryonic development. It was observed that shortly after puberty, females homozygous for this mutation entered reproductive senescence as defined by high levels of circulating gonadotropins, inability to respond either hormonally or functionally to superovulation, and a disrupted estrous cycle. Also, the ovaries completely lacked developing follicles and the endometrium was inactive. However, these mice had undergone complete sexual development as determined by age of vaginal opening, mammary gland histology, and sexual behavior. Thus, these animals closely mimic familial premature ovarian failure and may be useful models for study of the pathogenesis and treatment of this condition.

Animals↗
PubMed1992

Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation.

Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2 less than 0.0001 and p2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1992

The gene for the helix-loop-helix protein, Id, is specifically expressed in neural precursors.

While mammalian neurogenesis has been characterized extensively, the molecules involved in regulating neural cell determination and differentiation remain ill-defined. There is accruing evidence that various members of the basic helix-loop-helix (bHLH) protein family critically regulate these biological processes in a number of tissues. Id, a negative regulator of bHLH proteins, was found to exhibit peak gene expression during mouse embryogenesis with a striking pattern in the central nervous system. Id transcripts were specifically localized to undifferentiated neural precursors of the ventricular zone and were not present in their differentiated derivatives. In addition, in the peripheral nervous system, dorsal root ganglia sensory precursors, known to be undifferentiated while dividing, also expressed Id mRNA. However, in the sympathetic nervous system and adrenal medulla, where differentiation and division occur simultaneously in precursors, Id was not expressed. Since Id transcript abundance inversely correlated with differentiation, this protein, similar to its Drosophila homolog, extramacrochaetae, may play a negative regulatory role in neural differentiation.

Animals↗
PubMed1991

Germ-cell deficient (gcd), an insertional mutation manifested as infertility in transgenic mice.

A genetic analysis is necessary to gain a greater understanding of the complex developmental processes in mammals. Toward this end, an insertional transgenic mouse mutant has been isolated that results in abnormal germ-cell development. This recessive mutation manifests as infertility in both males and females and is specific for the reproductive organs, since all other tissues examined were histologically normal. A developmental analysis of the gonadal tissues demonstrated that the germ cells were specifically depleted as early as day 11.5 of embryonic development, while the various somatic cells were apparently unaffected. Therefore, the mutated locus must play a critical role in the migration/proliferation of primordial germ cells to the genital ridges of developing embryos. In addition, females homozygous for the mutation could potentially be a valuable animal model of a human syndrome, premature ovarian failure. This mutation has been named germ-cell deficient, gcd.

Animals↗
PubMed1991

Regional extraction of circulating norepinephrine, DOPA, and dihydroxyphenylglycol in humans.

Dihydroxyphenylglycol (DHPG) is the main intraneuronal metabolite of the sympathetic neurotransmitter, norepinephrine (NE), and dihydroxyphenylalanine (DOPA) the immediate product of the rate-limiting step in catecholamine biosynthesis. Simultaneous measurements of regional rates of appearance (spillovers) of NE, DOPA, and DHPG in plasma have the potential to provide unique information about aspects of sympathoneural function but have not actually been measured in humans. In the present study, spillovers of DHPG, DOPA, and NE in the heart, head, leg, and lungs, were estimated from regional extraction fractions of infused [3H]-1-NE, DHPG, and [13C6]DOPA or unlabelled DOPA in humans during cardiac catheterization. There was little cardiac extraction of DHPG (7 +/- SEM 2%) or DOPA (8 +/- 4%) but substantial extraction of NE (69 +/- 4%). Values for cardiac spillover of DHPG and DOPA therefore were similar to values for the arteriovenous increment times plasma flow (arteriovenous production rate), whereas the cardiac spillover of NE averaged about 7-times the NE arteriovenous production rate. Cardiac DHPG spillover (28 +/- 3 ng/min) exceeded the spillovers of NE (9 +/- 2 ng/min) and DOPA (15 +/- 4 ng/min). In contrast, cranial DOPA spillover (159 ng/min) exceeded those of NE and DHPG by 8- and 2-fold and accounted for about 1/10 of the total spillover of DOPA into arterial plasma. In the femoral vascular bed, arteriovenous production rates of NE and DHPG were unrelated to femoral spillovers of NE and DHPG. Arterial and regional clearances of [13C6]DOPA were similar to those of unlabelled DOPA. The results suggest that (1) endogenous NE, DOPA, and DHPG all are released into the bloodstream by the heart, head, and limbs of humans; (2) DHPG and DOPA are not co-released with NE; (3) cardiac arteriovenous production rates of DOPA and DHPG can be used to indicate cardiac spillover of these catechols, whereas the cardiac NE arteriovenous production rate substantially underestimates cardiac NE spillover; and (4) estimates of limb spillover of NE and DHPG require concurrent measurements of the corresponding regional clearances.

Arteries↗
PubMed1989

Atypical congenital mesoblastic nephroma. Report of a case with karyotypic and flow cytometric analysis.

Atypical congenital mesoblastic nephroma is a rare infantile renal tumor that may behave aggressively in older infants. A case of atypical congenital mesoblastic nephroma occurring in an 8-month-old hispanic male was analyzed by routine histopathologic, cytogenetic, and retrospective flow cytometric analysis for DNA ploidy. Light microscopy revealed marked hypercellularity. The karyotype was abnormal, with the following configuration: 45,XY,-1,-3,-9,-9,-15,-17,-21,+del(1)(q21q25),+der(3), t(3;9;15)(q23;p22;q11),+der(9),t(3;9;15) (q23;p22;q11),+der(9),t(9;?) (p?22;?),+r21, + mar. Retrospective DNA ploidy analysis revealed a DNA index of 1.0. The significance of karyotypic changes occurring in mesenchymal renal tumors of this type is currently unknown. Cytogenetic analysis might be of prognostic value in these potentially aggressive tumors.

DNA↗
PubMed1989

Hematogones: a multiparameter analysis of bone marrow precursor cells.

Morphologically distinct lymphoid cells with homogeneous, condensed chromatin and scant cytoplasm can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders. In some patients, these cells may account for greater than 50% of the bone marrow cells, creating a picture that can be confused with acute lymphoblastic leukemia (ALL) or metastatic tumor. Although originally called hematogones (HGs), a variety of other names have been proposed for these unique cells. The clinical significance of expanded HGs has not been resolved, and the biologic features of these cells are incompletely described. In this study, we correlate the clinical, morphologic, cytochemical, flow cytometric, molecular, and cytogenetic properties of bone marrow samples from 12 children with substantial numbers of HGs (range 8% to 55% of bone marrow cells). Diagnoses in these patients included anemia, four; neutropenia, one; anemia and neutropenia, one; idiopathic thrombocytopenic purpura, two; retinoblastoma, two; Ewing's sarcoma, one; and germ cell tumor, one. Flow cytometric analyses of bone marrow cells demonstrated a spectrum extending from early B-cell precursors (CD10+, CD19+, TdT+, HLA-Dr+) to mature surface immunoglobulin-bearing B cells in these patients, corroborating our morphologic impression of HGs, intermediate forms, and mature lymphocytes. DNA content was normal, and no clonal abnormality was identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies. Follow-up ranged from 3 months to 3 years. None of the patients has developed acute leukemia or bone marrow involvement by solid tumor. The possible role of HGs in immune recovery and hematopoiesis is presented.

Biomarkers, Tumor↗
PubMed1988

Outpatients: can we save time and reduce waiting lists?

The amount of time that one consultant urologist wasted on unnecessary administration while seeing outpatients was noted over six weeks. Searching for missing clinical data and the time spent on non-medical clerical tasks took up nearly half of the consultant's sessions. This seemed to be due to insufficient clerical and secretarial staff. Because low salaries are offered to such staff vast sums of money are being paid to agencies who are providing an appreciable number (40%) of the secretarial staff in our hospitals. Urgent action from the government is needed to remedy this and thus make substantial reductions in outpatient waiting lists nationally. It would greatly improve morale in this important sector of the health service without increasing total costs.

Appointments and Schedules↗