Autoantibodies to DNA in schizophrenia.
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Antibodies, Antinuclear↗
Biomedical subjects
S M Thomas
Publications and source records attributed to S M Thomas.
The role of thyroid fine needle aspiration (FNA) cytology in a District General Hospital setting.
The pilot study was undertaken to evaluate the role of FNA cytology in the clinical management of patients with thyroid swelling, in a District General Hospital (DGH) setting. One hundred and eleven patients were investigated over a period of 3 years, with a total of 142 fine needle aspirations. Statistical analysis showed a sensitivity of 71%, a specificity of 91% and a false negative rate of 2.7%. These results compare very favourably with other institutions. This study therefore shows that thyroid nodule FNA cytology can be performed in a DGH with a high standard of diagnostic accuracy, the results of which play a key role in patient management.
Biopsy, Needle↗
Histological changes associated with an artificial anterior cruciate ligament.
AIMS: To investigate the histopathological features of the synovial lining of the knee following implantation of an artificial cruciate ligament. METHODS: Eighty two patients underwent anterior cruciate ligament reconstruction for chronic, symptomatic instability of the knee. The cruciate ligament was reconstructed with a scaffold type prosthetic ligament. All patients underwent arthroscopy at the time of cruciate reconstruction and also as a "second look" procedure at a mean 26.5 months later, at which time synovial biopsy specimens were obtained in all cases. RESULTS: The most frequent histological finding was granulomatous synovitis in 48% (39/82) of patients. Particulate polyester debris produced a greater response than carbon fibres. In 24% (20/82), nonspecific inflammation was present and in 28% (23/82) the synovium was considered normal. When the prosthetic ligament was fully covered by soft tissue in-growth, a granulomatous reaction was present in 42% (24/57), irrespective of whether the ligament was partially or totally uncovered. Stabilisation of the joint did not prevent subsequent deterioration in the articular cartilage; other factors such as increasing patient age, interval between injury and reconstruction and altered knee kinematics after reconstruction are probably important. Granulomatous synovitis was not associated with progressive chondral changes. CONCLUSIONS: Although present in 48% of cases, granulomatous synovitis was not shown to have adverse effects on either chondral surface or the prosthetic material of the ligament. Rupture of the implant is caused by mechanical factors and granulomatous synovitis is not responsible for implant failure.
Adolescent↗
Women's health. Part II: Individual, environmental and economic factors affecting adherence to recommended screening practices for breast cancer.
In order for cancer mortality rates to be sufficiently reduced to meet the goals set by the National Cancer Institute, it is imperative that we broaden our understanding of the factors which affect participation in preventive health practices. Early detection and diagnosis of breast cancer are associated with participation in mammography, breast self-examination, and seeking medical care. A stratified random sample of women residing in Orleans Parish (40 to 65 years of age; annual family incomes < $40,000) were surveyed by telephone. Results of the survey were examined to determine the impact of individual, environmental, and economic factors on adherence to recommended screening practices for breast cancer. Results indicate a significant proportion of women are not adhering to recommended practices. Preventive health practices were positively related to physician recommendation of a mammogram and how the physician communicated with the patient; patient's income; belief in Powerful Others Locus of Control; and beliefs about the efficacy of early diagnosis and treatment. Fear of breast cancer was negatively related to preventive health practices. Findings highlight the utility of an ecological perspective in the development of secondary prevention strategies for breast cancer.
Adult↗
Polymerase patent problems.
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DNA-Directed DNA Polymerase↗
Cloning and sequencing of ATP sulfurylase from Penicillium chrysogenum. Identification of a likely allosteric domain.
Fungal (Penicillium chrysogenum) and yeast (Saccharomyces cerevisiae) ATP sulfurylases were shown to have very similar kinetic and chemical properties except that the fungal enzyme (a) contains a highly reactive Cys residue (SH-1) whose modification results in sigmoidal velocity curves (Renosto, F., Martin, R. L., and Segel, I. H. (1987) J. Biol. Chem. 262, 16279-16288) and (b) is allosterically inhibited by 3'-phosphoadenosine 5'-phosphosulfate (PAPS), while the yeast enzyme displays neither of these properties. The fungal enzyme subunit (64.3 kDa, 572 amino acids) is also larger than the yeast enzyme subunit (59.3 kDa, 521 amino acids). To correlate the unique allosteric properties of the fungal enzyme with specific structural features, we cloned and sequenced the ATP sulfurylase gene (aps) from P. chrysogenum. The yeast and fungal enzymes are homologous over the first 400 amino acids and contain two regions high in basic residues which are conserved in sulfurylases from Arabidopsis and the Riftia pachyptila (hydrothermal vent tube worm) chemolithotrophic symbiont. These regions may participate in forming the binding sites for MgATP2- and SO4(2-). The fungal enzyme has no sites for MgATP2- and SO4(2-). The fungal enzyme has no significant sequence homology to the yeast enzyme in the C-terminal 172 amino acids. This C-terminal region contains SH-1 (Cys-508) and has homology to MET14 (S. cerevisiae), CYSC (E. coli), and NODQ (Rhizobium meliloti), i.e. adenosine 5'-phosphosulfate (APS) kinase. The cumulative results suggest that (a) the allosteric PAPS binding site of P. chrysogenum ATP sulfurylase is located in the C-terminal domain of the protein and (b) that this domain may have evolved from APS kinase. In spite of the homology, this C-terminal region does not account for the APS kinase activity of P. chrysogenum. Fungal ATP sulfurylase has no significant homology to (or regulatory properties in common with) CYSD or CYSN, proteins reported to comprise E. coli ATP sulfurylase (Leyh, T., Vogt, T. F., and Suo, Y. (1992) J. Biol. Chem. 267, 10405-10410).
Allosteric Site↗
Luria-Delbrück fluctuation experiments: design and analysis.
Luria and Delbrück, in a seminal paper, introduced fluctuation analysis primarily as a means to elucidate the timing of mutation in relation to the imposition of selective conditions. Their work, and subsequently that of LEA and COULSON, established also a basis for measuring the frequency of mutational events. The several estimators proposed by these authors differ both in complexity and in efficiency, and the published literature relies mainly on the less efficient but computationally trivial estimators. The estimators as originally proposed assume that all mutants occurring in culture will be counted in the subsequent assay, but a relaxation of this assumption suggests an alternative experimental design and alternative estimators which offer advantages over those currently in common use.
Biometry↗
Cloning and nucleotide sequence of the Streptococcus pneumoniae hyaluronidase gene and purification of the enzyme from recombinant Escherichia coli.
A gene bank of Sau3A1-generated Streptococcus pneumoniae type 23 DNA fragments was constructed in Escherichia coli K-12 with the low-copy-number cosmid vector pOU61cos. Clone lysates were screened by immunoblotting using a mouse antiserum raised against a crude pneumococcal hyaluronidase preparation. One immunoreactive clone was isolated, and it produced high level of hyaluronidase activity. This clone contained a recombinant cosmid (designated pJCP800) with an approximately 35-kb DNA insert, and the putative hyaluronidase coding sequence was subcloned into pBluescript SK as a 3.8-kb PstI-ClaI fragment (designated pJCP802). The complete nucleotide sequence of this insert was determined. The region included an open reading frame sufficient to encode a polypeptide with an M(r) of 107,751. An active hyaluronidase with an M(r) of approximately 89,000 was purified to homogeneity from E. coli DH5 alpha(pJCP802). N-terminal amino acid sequence analysis of the purified protein suggested that translation initiation was occurring primarily at a TTG codon within the major open reading frame. However, immunoblot analysis using antiserum raised against the purified 89-kDa hyaluronidase indicated that E. coli DH5 alpha(pJCP802) also expressed the 107-kDa form of the enzyme. This antiserum labelled a 107-kDa protein in partially purified hyaluronidase preparations from S. pneumoniae. The hyaluronidase activity in this pneumococcal extract was also neutralized by the antiserum.
Amino Acid Sequence↗
Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains.
Src homology 3 (SH3) domains mediate protein-protein interactions necessary for the coupling of cellular proteins involved in intracellular signal transduction. We previously established solution-binding conditions that allow affinity isolation of Src SH3-binding proteins from cellular extracts (Z. Weng, J. A. Taylor, C. E. Turner, J. S. Brugge, and C. Seidel-Dugan, J. Biol. Chem. 268:14956-14963, 1993). In this report, we identified three of these proteins: Shc, a signaling protein that couples membrane tyrosine kinases with Ras; p62, a protein which can bind to p21rasGAP; and heterogeneous nuclear ribonucleoprotein K, a pre-mRNA-binding protein. All of these proteins contain proline-rich peptide motifs that could serve as SH3 domain ligands, and the binding of these proteins to the Src SH3 domain was inhibited with a proline-rich Src SH3 peptide ligand. These three proteins, as well as most of the other Src SH3 ligands, also bound to the SH3 domains of the closely related protein tyrosine kinases Fyn and Lyn. However, Src- and Lyn-specific SH3-binding proteins were also detected, suggesting subtle differences in the binding specificity of the SH3 domains from these related proteins. Several Src SH3-binding proteins were phosphorylated in Src-transformed cells. The phosphorylation of these proteins was not detected in cells transformed by a mutant variant of Src lacking the SH3 domain, while there was little change in tyrosine phosphorylation of other Src-induced phosphoproteins. In addition, the coprecipitation of v-Src with two tyrosyl-phosphorylated proteins with M(r)s of 62,000 and 130,000 was inhibited by incubation with a Src SH3 peptide ligand, suggesting that the binding of these substrate proteins is dependent on interactions with the SH3 domain. These results strongly suggest a role for the Src SH3 domain in the recruitment of substrates to this protein tyrosine kinase, either through direct interaction with the SH3 domain or indirectly through interactions with proteins that bind to the SH3 domain.
3T3 Cells↗
Composite glandular-carcinoid tumour of the terminal ileum.
AIMS: To investigate a female patient with a tumour mass of the terminal ileum, to define the nature of the tumour, and to correlate its morphology and behaviour with similar types of tumours of the large intestine and stomach. METHODS: Tissues obtained at colonoscopy, from hemicolectomy specimens, and from liver and peritoneal biopsy specimens were studied macroscopically, microscopically, histochemically, and immunohistochemically for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and S100 protein. RESULTS: Macroscopic examination showed a tumour of the terminal ileum protruding into the caecum. Microscopically the tumour showed two components, one adenoma with moderate dysplasia and the other carcinoid tumour. The adenomatous component stained positively for EMA and CEA and negatively for NSE. The carcinoid component stained positively for NSE and negatively for EMA and CEA. Histochemically the carcinoid area was argyrophil positive and argentaffin negative. Only the carcinoid had metastasised, to the liver, peritoneum, and the lymph nodes, at the time of diagnosis. CONCLUSION: The morphological, histochemical, and immunohistochemical findings confirm the diagnosis of a composite adenoma-carcinoid tumour of the terminal ileum.
Adenoma↗
Effect of high-dose verapamil administration on the Ca2+ channel density in rat cardiac tissue.
It is well known that beta-adrenergic receptors will down-regulate in the presence of high circulating levels of beta-adrenergic agonists over extended periods of time. However, less is known with respect to the effect of Ca2+ channel antagonist on their receptors. The purpose of this study was to determine if chronic administration of high dosages of verapamil (in the toxic range) could alter the density of Ca2+ channels in the heart as determined by [3H]PN 200-110 binding. A range of high verapamil concentrations was administered to rats via s.c. implantable slow-release pellets or s.c. injection. An increasing rate of mortality was observed as the dose of verapamil administered increased. Quantitation of serum verapamil concentrations demonstrated that the s.c. slow release implantable pellets were not releasing the drug evenly and instead released toxic quantities of drug during the first 24 h after implantation. Serum verapamil levels determined from verapamil-injected animals demonstrated a dose-dependent increase in circulating levels. No significant alterations in Ca2+ channel characteristics (Bmax and Kd) were noted in cardiac tissue obtained from either treatment regime. Our results demonstrate that implantable pellets are not a reliable administration method for verapamil and cardiac Ca2+ channels are unusually resistant to biochemical alterations even after administration of verapamil dosages in the toxic range.
Animals↗
Women's health: early detection and screening practices for breast and cervical cancer.
A telephone survey of Orleans Parish residents (25 to 65 years old; annual family incomes < $40,000) was conducted to explore cancer-related knowledge, beliefs, and practices. This paper presents descriptive information about knowledge and practices pertinent to early detection of cancer (breast self-examination, Pap smear, and mammogram) among women (N = 315). Income-related differences were observed. Women in the lower income group were less likely to routinely practice breast self-examination, and also less likely to have had a recent Pap smear or mammogram. Gaps in knowledge regarding the purpose of Pap smears and mammograms were noted. This sample of women reported their physicians are not routinely recommending Pap smears or mammograms. Findings highlight the need for community education programs to enhance awareness of the purpose and importance of cancer screening practices, particularly among the poor. In addition, all medical professionals who have contact with women need to reiterate the importance of regular participation in cancer-screening practices.
Adult↗
IFN-gamma-mediated antimicrobial response. Indoleamine 2,3-dioxygenase-deficient mutant host cells no longer inhibit intracellular Chlamydia spp. or Toxoplasma growth.
The role of indoleamine 2,3-dioxygenase (IDO) in IFN-gamma-mediated inhibition of intracellular parasite growth has been examined previously, although earlier work has been largely correlative. In this study, we defined more completely the role of IDO in the IFN-antimicrobial response. Two mutant cell lines, derived from ME180 cells and exhibiting reduced IDO activity (IR3B6A, IR3B6B) were characterized to determine if they retained the capacity to inhibit intracellular Chlamydia and Toxoplasma growth. Mutant cells treated with IFN-gamma exhibited reduced capacity to suppress pathogen growth. The expression of several IFN-regulated genes also was measured to confirm that the inability to inhibit pathogen growth was because of the lack of IDO. The expression of class II MHC, intracellular adhesion molecule-1, MxA, and P68 kinase genes was induced in the IFN-gamma-treated wild type ME180 cells, but was variable in the mutant cell lines, supporting the hypothesis that IFN-gamma-induced production of IDO is a key IFN-gamma-mediated antimicrobial mechanism.
Animals↗
Analysis of the 18S ribosomal RNA gene of Strongyloides stercoralis.
The entire 1766 bases of the 18S rRNA gene of Strongyloides stercoralis have been sequenced. The gene has a 38% G+C content. Although it is similar in length to the 18S rRNA gene of Caenorhabditis elegans, the only other completely sequenced nematode 18S rRNA gene, it is only 69% identical. Closely related helminths will need to be sequenced in order to delineate sequences specific for the diagnosis of strongyloidiasis.
Animals↗
Extreme cold sensitivity of Salmonella typhimurium umu clones, effects of the umu region and flanking sequences.
The umuDC operons of both Salmonella typhimurium and Escherichia coli encode proteins which are essential for mutagenesis following exposure to ultraviolet radiation or a variety of chemicals. However S. typhimurium is less mutable and its umu operon appears to be less active for reasons that are unknown. This study shows that pBR322-based plasmids carrying cloned umuDC operons of either species confer cold sensitivity on both an E. coli umuC strain and a S. typhimurium pSLT- strain. Both S. typhimurium and E. coli umu clones make these lexA+ strains moderately cold-sensitive, but sensitivity produced by the cloned S. typhimurium umuDC operon is extreme when flanking regions of the chromosome are also present. Such instability might be significant in terms of explaining the polymorphisms seen in the regions of the chromosomes of Enterobacteriaceae surrounding the umuDC operon. In S. typhimurium this extreme cold sensitivity was almost certainly responsible for the delayed recognition of a chromosomal umuDC operon.
Cold Temperature↗
Hypoplastic crisis with persistent arthralgia and prolonged parvovirus B19 viraemia detected by polymerase chain reaction.
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Adult↗
Changes in heat shock protein 70 and ubiquitin mRNA levels in C1300 N2A mouse neuroblastoma cells following treatment with iron.
We have shown that following heat shock (42.5 degree C for 30 min), mouse-derived C1300 N2A neuroblastoma cells contain increased levels of mRNA coding for the inducible form of heat shock protein 70 and for ubiquitin. Incubation of C1300 cells with iron also induces an elevation in content of mRNAs coding for the same two proteins that can be blocked by alpha-tocopherol and desferrioxamine. Iron was shown to increase mitochondrial and lysosomal activities in differentiated C1300 N2A cultures, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and neutral red cytotoxicity assays. These responses were not initially associated with any loss of viability, as assessed by the lactate dehydrogenase release assay. These results suggest that there is production of cytoprotective heat shock proteins in response to iron-mediated cell damage, probably involving free radical generation, in neural cells. The apparent stress response of vulnerable neurones in human neurodegenerative diseases, particularly Parkinson's disease, may be induced by iron-mediated free radical production in degenerating neurones, making investigation of the mechanism of free radical-induced responses in neuronal cells of special interest.
Animals↗
Isolated splenic metastases from colon carcinoma.
It is generally accepted that splenic metastases from colorectal carcinoma occur concurrently with widespread dissemination of the tumor. The case reviewed is notable for its long disease-free interval, isolated splenic metastasis and favorable-outcome postsplenectomy. It represents the fourth case report in the English literature of surgical resection for an isolated splenic metastasis from colorectal carcinoma.
Adenocarcinoma↗