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Biomedical subjects

D Todd

Publications and source records attributed to D Todd.

At least 91 records · Page 5Linked to original sources
PubMed1994

Some biological and physico-chemical properties of porcine circovirus.

Some important biological and physico-chemical characteristics of porcine circovirus are reported. These include a study on the host distribution in nature, levels of colostrum-derived antibodies in piglets from sero-positive sows and the susceptibility of a range of cell cultures to infection with this virus. The results of haemagglutination studies, resistance to pH 3, chloroform and heat are also reported as are comparative buoyant densities and sedimentation coefficients of porcine circovirus and chicken anaemia virus.

Animals↗
PubMed1994

A single chicken anemia virus protein induces apoptosis.

Chicken anemia virus (CAV) causes cytopathogenic effects in chicken thymocytes and cultured transformed mononuclear cells via apoptosis. Early after infection of chicken mononuclear cells, the CAV-encoded protein VP3 exhibits a finely granular distribution within the nucleus. At a later stage after infection, VP3 forms aggregates. At this point, the cell becomes apoptotic and the cellular DNA is fragmented and condensed. By immunogold electron microscopy VP3 was shown to be associated with apoptotic structures. In vitro, expression of VP3 induced apoptosis in chicken lymphoblastoid T cells and myeloid cells, which are susceptible to CAV infection, but not in chicken embryo fibroblasts, which are not susceptible to CAV. Expression of a C-terminally truncated VP3 induced much less pronounced apoptosis in the chicken lymphoblastoid T cells.

Amino Acid Sequence↗
PubMed1994

Human osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase.

Nitric oxide (NO) is a short-lived free radical that plays an important regulatory role in several biological processes. Cytokines such as interleukin-1, tumor necrosis factor, and interferon-gamma have been shown to stimulate NO production in many cells types. Although these cytokines are known to have potent effects on bone remodeling and osteoblast function, the role of NO as an effector molecule in bone has been little studied. Here we investigate the effects of cytokines and calciotropic hormones on NO production by human osteoblast-like cells (hOB) and the role of NO as a modulator of osteoblast growth. Unstimulated hOB produced little NO, as reflected by measurement of nitrite concentrations in hOB-conditioned medium. NO production was not significantly altered by PTH and 1,25-dihydroxyvitamin D or human recombinant interleukin-1 beta (10 U/ml), tumor necrosis factor-alpha (25 ng/ml), and interferon-gamma (100 U/ml) individually. Combinations of all three cytokines at these concentrations, however, dramatically increased both NO generation and cGMP production. The stimulatory effect of cytokines on NO production began 12 h after exposure and was inhibited by cycloheximide, actinomycin-D, dexamethasone, and the competitive inhibitor of NO synthase L-NG-monomethylarginine. Reverse transcription/polymerase chain reaction analysis of hOB RNA, followed by direct sequencing of the amplified products, showed that hOB express the inducible, rather than the endothelial or neuronal, forms of NO synthase. Cytokine-induced increases in NO production were associated with a marked inhibition of [3H]thymidine uptake to less than 10% of that observed in control cultures. Abrogation of NO synthesis with L-NG-monomethylarginine under these conditions significantly increased [3H]thymidine uptake to approximately 20% of the control value, suggesting that NO may partly be responsible for the inhibition of osteoblast proliferation induced by these cytokines. Our data indicate that proinflammatory cytokines induce NO production in osteoblast-like cells and show and that this mediator plays a role in regulating cell growth. These findings may have important implications for the pathogenesis and management of bone loss in diseases associated with cytokine activation, such as rheumatoid arthritis.

Amino Acid Oxidoreductases↗
PubMed1994

Parents' beliefs about cholesterol and its effects on their children.

A random sample of parents of primary grade children (N = 500) was obtained from two higher socioeconomic-status suburban elementary schools. The respondents (n = 277) were well educated (92% attended or graduated from college), white (92%), primarily higher in socioeconomic status (79% earned more than $50,000/year), and female (70%). Two-thirds of the parents believed that all elementary school children should have their cholesterol levels checked, 70% believed high cholesterol in children was serious, yet only 21% believed their child would develop a high cholesterol level. To control their children's cholesterol level, the majority of parents (73%) made lifestyle changes for their children since the majority believed high cholesterol levels would clog arteries (95%) and cause heart disease (90%). Parents most often received their information on cholesterol from magazines (73%), newspapers (62%), and physicians (52%).

Adult↗
PubMed1994

Childhood acute lymphoblastic leukaemia and aplastic anaemia.

Aplastic anaemia (AA) can be associated with disorders that are known to exhibit clonal haematopoiesis, like paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). It appears that the long term survivors of severe AA treated with immunosuppressive agents such as ATG have a continuing, late mortality caused by the evolution of clonal disorders which are not usually seen when bone marrow transplant is used. In children, typical AA may precede the onset of acute lymphoblastic leukemia (ALL). The aplastic phase is often transient and remission may be spontaneous or rapidly induced by steroid, and followed a few months later by acute leukaemia. This modality of presentation may be observed in up to 2-3% of all cases of paediatric ALL. A 13-year old girl who presented with two spontaneously reversible episodes of marrow aplasia has been reported recently. She developed ALL 8 months later. Southern analysis showed identical clonal immunoglobulin heavy chain gene rearrangement bands in her leukaemic cells as well as the marrow cells obtained at the two aplastic episodes. Hypoxanthine phosphoribosyltransferase polymorphism studies showed that all the ALL blast cells, bone marrow and peripheral cells during the two aplastic episodes all exhibited clonal haematopoiesis with the same X-chromosome inactivated. This case provides strong evidence that AA and ALL can represent evolution of the same abnormal clone.

Adolescent↗
PubMed1994

4th Seah Cheng Siang Memorial Lecture. Primary gastrointestinal lymphoma in Hong Kong.

Many primary gastrointestinal lymphomas (PGL) are treatable and carry a good prognosis, particularly of localized and of "low grade" malignancy. In general, the stomach is the most commonly involved site followed by the small and then large intestines. The incidence of gastric lymphoma may be on the rise, and the response of lymphoma arising from gastric Mucosa Associated Lymphoid Tissue (MALT) to treatment of the co-existing Helicobacter pylori infection has added a new dimension to the study of PGL. Most PGLs are histologically aggressive and those involving the intestines tend to present late. In a series of 425 adult Chinese patients with PGL seen in Hong Kong between 1975 and 1993, there were 230 males and 195 females with a median age of 53 years. Sites of involvement were the oesophagus in 3, the stomach in 238, small intestines in 131 and large intestines in 53. The majority were of diffuse large cell, small cell, mixed or immunoblastic histology (Working Formulation) and 90% were of B cell origin. At presentation 70.6% had stage II, IV disease (Manchester Classification) and 64.7% had B symptoms. The most common presenting clinical features were abdominal pain, gastrointestinal bleeding, anorexia, vomiting and weight loss. Perforation occurred in 76 patients. Surgery was carried out in 318 (74.8%), radiotherapy in 161 (37.9%) and all patients with advanced diseases received chemotherapy, with or without radiotherapy. The overall 5-year survival was 75% in patients with low grade histology and 70% in those with clinical stage I and II disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Poor outcome of intensive chemotherapy for adult acute lymphoblastic leukemia: a possible dose effect.

Fifty consecutive adult patients with acute lymphoblastic leukemia (ALL) were treated with an intensive cyclical chemotherapy and the mean received dose of individual cytotoxic drug was retrospectively studied. The median age was 28 years. Twenty-one (43%) had white blood cell (WBC) count over 30 x 10(9)/l. Of the 26 patients with successful cytogenetic studies, ten (28%) had unfavorable clonal chromosomal abnormalities (four Philadelphia chromosome, six others). A high complete remission (CR) rate (86%) was achieved. This was associated with delivery of 100% of the planned dosage of vincristine, prednisone, and daunorubicin at induction. Dose reduction of asparaginase, the fourth drug in the induction protocol, was recorded in 20 (40%) patients. The CR rate of these patients was not adversely affected. Dose reduction was recorded during consolidation (38 of 43 remitters) and maintenance (18 of 20 remitters) as a result of treatment toxicity. The mean received dose of teniposide, Ara-C, asparaginase, mercaptopurine, and methotrexate was 73% (SD 7%), 73% (SD 7%), 62% (SD 41%), 65% (SD 15%) and 73% (SD 17%) of the planned dosage, respectively. The 5-year overall survival and leukemia-free survival (LFS) were 11% (95% CI: 0-27%) and 13% (95% CI: 0-26%), respectively. Even standard-risk patients had 4-year LFS of only 26% (95% CI: 0-57%). Among 36 remitters not withdrawn from consolidation, there were 29 treatment failures after a median follow-up of 42 months; 25 (86%) of these were leukemia relapse, three (10%) were toxic death during consolidation, and one patient (4%) died from therapy-related myelodysplastic syndrome. We postulate inadequate drug delivery during postremission therapy contributed to the high relapse rate in the whole group as well as the standard-risk patients.

Adult↗
PubMed1993

Detection of immunoglobulin gene rearrangement in lymphoid malignancies of B-cell lineage by seminested polymerase chain reaction gene amplification.

Seminested polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity-determining region 3 of the immunoglobulin (Ig) gene heavy chain from the malignant cell specimens of patients with leukemias and lymphomas of B-cell lineage. Two different pairs of primers were used sequentially. Twenty of the 27 (74%) acute lymphoblastic leukemia (ALL) patients, 14 of 19 (74%) chronic lymphocytic leukemia (CLL) patients and eight of 20 (40%) non-Hodgkin's lymphoma (NHL) patients, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by the seminested PCR. False-negative results appeared to occur more commonly in cases of lymphoma. The PCR analysis was also less likely to be positive if one-stage PCR studies with either pair of primers were both negative. The seminested PCR technique was found to have a high sensitivity of detecting malignant cells at the level of 0.02%. The clinical application of this assay needs to be investigated further.

Base Sequence↗
PubMed1993

False non-paternity in a family for prenatal diagnosis of beta-thalassaemia.

Initial screening for the common beta-thalassaemia mutations with allele-specific oligonucleotide probes in an at-risk family suggested non-paternity. Subsequent DNA fingerprinting of the members proved otherwise. The mother had a codon 41/42 frameshift mutation and the father's defect, determined by direct sequencing of PCR-amplified beta gene, was a codon 43 nonsense mutation. In the affected children, the close proximity of these two defects resulted in the absence of a hybridization signal to the normal probe in that region and a wrong assumption of homozygosity for the codon 41/42 mutation. The non-reactivity of the father's amplified DNA to the codon 41/42 thalassaemic probe accounted for the initial wrong conclusion of non-paternity. Since prior screening for beta-thalassaemia mutations is done in all prenatal diagnosis programmes and concomitant inheritance of these two defects is relatively common in the Chinese, this 'artefact' of false non-paternity is worth noting.

Adult↗
PubMed1993

Comparison of serological tests for the diagnosis of Chlamydia psittaci infection of sheep.

An enzyme-linked immunosorbent assay (ELISA) was developed and compared with the complement fixation test (CFT) and the indirect immunofluorescence antibody test (IIFAT) for the detection of antibodies to C. psittaci in sheep. Field sera and experimental sera from aborting ewes, subclinically infected sheep and vaccinated sheep were used. The ELISA and IIFAT were much more sensitive than the CFT. Agreement between the CFT and ELISA varied between 50% and 98%, while agreement between the IIFAT and ELISA varied between 70.5% and 94.3%. The specificity of IIFAT and ELISA with regard to the identification of animals which may be a source of ovine abortion strains of C. psittaci was critically assessed, using antigen preparations derived from an abortion isolate and from a non-abortion isolate of C. psittaci. Indirect immunofluorescence was shown to be the more discerning test.

Abortion, Veterinary↗
PubMed1993

Comparison of ovine abortion and non-abortion isolates of Chlamydia psittaci using inclusion morphology, polyacrylamide gel electrophoresis, restriction endonuclease analysis and reactivity with monoclonal antibodies.

Twelve reference and four Northern Ireland ovine Chlamydia psittaci isolates including ovine abortion, faecal, conjunctivitis and arthritis isolates were compared. Inclusion morphology was shown to provide a useful means of differentiating the abortion and the non-abortion isolates studied. Identical SDS-PAGE polypeptide profiles were produced by the ovine abortion isolates. The polypeptide profiles of the non-abortion isolates were similar to one another and clearly distinct from the abortion isolate profiles. The restriction endonuclease profiles of the abortion isolates were remarkably similar whereas different profiles were produced by most of the non-abortion isolates. Monoclonal antibodies were prepared and characterized. A number of these reacted with all the isolates of chlamydia tested. Three mAbs reacted exclusively with the ovine abortion isolates while four mAbs reacted exclusively with a number of the faecal isolates.

Abortion, Veterinary↗
PubMed1993

Allergic contact dermatitis from para-tertiary-butylphenol-formaldehyde resin (PTBP-F-R) in Northern Ireland.

Over the past 5 years, 2270 patients with suspected allergic contact dermatitis were patch tested in our clinic to the European standard series of allergens. 7 patients (0.3%) showed a positive reaction (> or = +) to PTBP-F-R. In 3 (42.9%) of these patients, the allergen was traced to adhesives but no allergen source was determined in the remainder (57.1%). On the basis of these findings, it is questionable whether PTBP-F-R alone should routinely be included in the European standard series.

Adult↗
PubMed1993

Mercury allergy in a contact dermatitis clinic in Northern Ireland.

441 consecutive patients (294 female, 147 male) with suspected contact dermatitis were patch tested to the European standard series, mercury metal (1% pet), ammoniated mercury (1% pet.), and mercuric chloride (0.1% aq.). 14 patients (3.2%), 12 of whom were female, showed a positive response to 1 or more mercury compounds; none reacted to mercuric chloride alone. Primary sensitization was most likely due to either inoculation with vaccines containing merthiolate preservatives or amalgam dental restorations. Mercury allergy was of historical clinical relevance in only 2 patients, both women who developed gingivostomatitis following insertion of amalgam dental fillings. 1 of these women subsequently developed allergic contact dermatitis from contact lens solutions, shampoos and cosmetics which contained mercury preservatives. On the basis of these findings, we recommend patch testing with both metallic mercury and ammoniated mercury in patients with suspected mercury allergy.

Adult↗
PubMed1993

The use of "nonanatomic" pulmonary resection in infants with extensive congenital adenomatoid malformation of the lung.

In three infants with extensive congenital adenomatoid malformation of the lung, a method of nonanatomic pulmonary resection permitted preservation of small superiorly positioned pulmonary remnants. These remnants then demonstrated a surprising capacity for expansion, growth, and function during follow-up periods of 5 years, 9 months; 7 years, 6 months; and 19 years. Thus far, this small experience indicates that this method of management does not appear to entail greater short- or long-term risks than the alternative procedure of pneumonectomy.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1992

Non-aggressive therapy for chronic myeloid leukaemia in blastic transformation.

A total of 40 patients presenting with chronic myeloid leukaemia in blastic transformation were treated with a non-aggressive chemotherapy regimen consisting of vincristine, cytosine arabinoside and thioguanine. Remissions were achieved by 3/10 (30%) patients displaying lymphoid transformation (remission duration, 2, 3, and 5 months, respectively) and by 5/30 (17%) subjects exhibiting myeloid changes (duration 2+, 4, 4, 5 and 7 months, respectively). Myelosuppression was the major toxicity and non-haematological toxicities were mild and acceptable. The median survival of patients exhibiting lymphoid and myeloid blastic transformation as measured from the time of transformation was 6 and 3 months, respectively, but the difference was not statistically significant. Three subjects displaying lymphoid transformation and five showing myeloid changes survived for greater than 12 months after the time of transformation.

Acute Disease↗
PubMed1992

Characterization of viral DNAs from cells infected with chicken anaemia agent: sequence analysis of the cloned replicative form and transfection capabilities of cloned genome fragments.

The viral DNAs induced by the unclassified animal virus, chicken anaemia agent (CAA), during replication in MDCC-MSB 1 cells have been investigated. Analyses after S1 nuclease, restriction endonuclease and denaturation treatments indicated that infected cell extracts contained genome-size, single-stranded DNA (M(r) 2.3 kb), closed and open circular, double-stranded replicative form (RF) DNAs (M(r) 2.3 kbp) and a population of smaller double-stranded DNAs (M(r) 0.8 kbp). Recombinant plasmids containing 2.3 kbp CAA RF fragments cloned at the PstI, BamHI and EcoRI sites failed to transfect MDCC-MSB 1 cells. However, one plasmid, which contained two 2.3 kbp CAA RF fragments ligated in tandem at the PstI site, and cloned 2.3 kbp PstI, BamHI and EcoRI fragments, excised from their respective plasmids by restriction endonuclease digestion, were capable of transfection. The nucleotide sequence of the circular genome (2298 bp) of the Cux-1 isolate of CAA has indicated the presence of three overlapping open reading frames (ORFs) of 52 kDa, 24 kDa and 13 kDa on one strand. The existence of these ORFs was corroborated by analyses of partial sequences from three other isolates. The non-coding region of the CAA genome contained sequences with putative regulatory function. These results are discussed in relation to the "rolling circle" model of DNA replication.

Amino Acid Sequence↗