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S J Johnson

Publications and source records attributed to S J Johnson.

At least 19 recordsLinked to original sources
PubMed2003

An audit of the positive predictive value of high-grade dyskaryosis in cervical smears: 2001-2002.

The positive predictive value (PPV) of high-grade dyskaryosis for cervical intraepithelial neoplasia grade 2 (CIN2) or worse on histology is published annually for the laboratories in the UK National Health Service Cervical Screening Programme (NHSCSP). The PPV fell in 2001 compared with 2000 for four of the five consultants reporting cervical smears in our laboratory, the greatest fall being from 91.6% to 77.9%. Investigation of the possible reasons for the fall suggested the main cause lay outside the laboratory in the type of biopsy taken at colposcopy. We conclude that biopsy type affects accuracy of PPV calculations. There is variation in collection and submission of KC61 data including PPV across laboratories. This factor needs to be taken into account when publishing and comparing laboratory data for the NHSCSP.

Biomarkers, Tumor↗
PubMed2002

How predictive is a cervical smear suggesting glandular neoplasia?

The prevalence of endocervical adenocarcinoma and its precursors has increased, in part due to increased diagnostic awareness of these lesions. To date, limited information has been published regarding the predictive value of glandular abnormalities in cervical smears. This study details the histological follow up of 418 cervical smears showing glandular abnormality, reported in our department over a six year period from 1993 to 1998. Histological follow up was available for 395 of the 418 smears (94.50%). The overall positive predictive value (PPV) for this group of smears was 72.66% for either significant glandular or squamous pathology (at least low grade cervical glandular intraepithelial neoplasia or CIN2 on follow up biopsy), and 55.70% for significant glandular pathology alone. Examination of subcategories of abnormal glandular smear showed that the PPV increased with the degree of abnormality reported within the smears.

Adenocarcinoma↗
PubMed2001

How predictive is a cervical smear suggesting invasive squamous cell carcinoma?

How predictive is a cervical smear suggesting invasive squamous cell carcinoma? Features have been described in severely dyskaryotic cervical smears that suggest frankly invasive or microinvasive squamous cell carcinoma. These are reported in three separate categories in our department. The aim of the current study was to assess the positive predictive value of these categories for invasive disease on histology. All smears reported in these categories over a five year period were correlated with the histology results. 527 smears were assessed. The positive predictive value of a smear suggesting frank invasion was 55.7% for all invasive squamous carcinomas and 40% for stage IB or above. Smears suspicious of invasion or microinvasion predicted invasive disease in 22.3% and 17.2%, respectively, most carcinomas being stage IA. Invasive squamous cell carcinoma may be predicted to a limited degree by cervical cytology especially when the smear suggests frank invasion.

Adult↗
PubMed2001

The importance of intracytoplasmic DPAS positivity in fine needle aspirates of breast lesions.

AIMS: For many years the presence of strong intracytoplasmic periodic acid Schiff (PAS) positive, diastase resistant (DPAS) staining within atypical cells has been used in this laboratory as a marker for carcinoma in fine needle aspirates from breast lesions. The aim of the current study was to document such DPAS positivity across the spectrum from benign to malignant breast disease and assess its value in the upgrading of cytology reports. METHODS: Over a six month period, 315 aspirates were studied, each having sufficient cellular material for DPAS staining to be carried out on one whole slide. DPAS staining was recorded semiquantitatively as negative, equivocal, or positive (+, ++, or +++). The cytology results were correlated with any subsequent histology performed on these patients. RESULTS: DPAS positive material was seen in both intracellular and extracellular locations. Care was needed in its interpretation. Occasional cells with apparently genuine intracytoplasmic positivity (+) were found in both benign and malignant cases. Frequent or particularly strong intracellular DPAS positivity (++, +++) correlated best with malignancy. Two cases were reliably upgraded from immediate reports suspicious of malignancy to final reports diagnostic of malignancy on the basis of the intracytoplasmic DPAS staining. CONCLUSION: Strict criteria are required for the interpretation of intracytoplasmic DPAS positivity and routine cytological appearances should also be taken into account. Weak positivity in occasional cells, especially in flat epithelial sheets, may be seen in benign lesions and is not reliable as a marker of malignancy. DPAS positivity with internal structure and producing nuclear indentation, especially in dissociated or atypical cells, correlates well with malignant histology and can be reassuring in the cytological diagnosis of malignancy.

Amylases↗
PubMed2000

An investigation into the role of oxygen free radical scavengers in preventing polymethylmethacrylate-induced necrosis in an osteoblast cell culture.

This study examined the effect of polymethylmethacrylate (PMMA) on osteocytic necrosis and the role of free radical scavengers in minimizing this damage. Bovine osteoblast cells with a characteristic phenotype were seeded at a density of 4x10(4) cells/cm2 and cultured in a DMEM supplemented with 10% fetal calf serum. A transwell insert with 2 cc of PMMA was suspended above the culture, and a time log response curve was established following elusion of free radicals around the osteoblast media. Chemiluminescence was used to determine quantitative free radical release. Using a Student's two-tailed t test there was a significant difference in the amount of hydroxyl radical released at 1-6 hours compared with controls (P=.028). Using histologic markers, there was a significant correlation between the use of PMMA and osteoblast cell necrosis. Transwell plates were coated with varying concentrations of mannitol, a known hydroxyl radical scavenger. A log dose response curve was established. There was a clear statistical association between a 10% mannitol solution and a reduction in the free radical release from PMMA (P=.03). Similarly, using Trypan blue histologic staining, there was a significant reduction in PMMA-induced cell necrosis when 10% mannitol was used as a scavenger (P=.01). A Rockwell superficial hardness test was used to determine whether mannitol had any effect on the surface hardness of the polymer. No statistical difference could be found between those treated with mannitol and controls at a depth of up to 1 mm. These results demonstrate hydroxyl radical is released from the polymerization reaction of PMMA. These radicals cause cell death in an osteoblast culture medium. This has been addressed using a 10% mannitol solution, which reduced cell necrosis.

Cells, Cultured↗
PubMed2000

Thyroid aspiration cytology in Newcastle: a six year cytology/histology correlation study.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a well-established technique for pre-operative investigation of thyroid nodule(s). Thyroid FNAC was introduced in the teaching hospitals of Newcastle upon Tyne in 1981, initially with a small group of clinicians as aspirators. Audit results for 1981-1986 inclusive showed an unsatisfactory rate of 25.3% and prediction of malignancy with a sensitivity of 93.5%. FNAC has become more popular locally for the investigation of thyroid disease and the number of clinicians performing aspirates has increased. The results for recent years have, therefore, been audited. METHODS: Medical records were reviewed for 239 patients with a dominant thyroid nodule who had FNAC carried out in the 6 year period 1990-1995 and subsequent partial or complete thyroidectomy. RESULTS: Histology of thyroid specimens showed 60 follicular adenomas and 34 malignant lesions (including 19 papillary, 10 follicular and 3 medullary carcinomas, one lymphoma and one follicular neoplasm with indeterminate malignant potential). A total of 302 FNAC had been carried out on these 239 patients. On cytological grounds the unsatisfactory sample (AC0 and AC1) rate was 43.1% on initial aspiration which was reduced to 32.2% on repeated aspiration. FNAC predicted neoplasia (AC3, AC4 and AC5) with a sensitivity of 86.8%, a specificity of 67.0%, a negative predictive value of 87.5% and a positive predictive value of 65.5%. Malignancy was predicted by FNAC (AC3, AC4 and AC5) with a sensitivity of 88.9%. A FNAC report of AC5 had a positive predictive value for malignancy of 100%. CONCLUSIONS: FNAC is an invaluable and minimally invasive procedure for the pre-operative assessment of patients with a dominant thyroid nodule. It is, however, important that the number of aspirators and cytopathologists be kept small to maintain expertise and also that the results of FNAC be subjected to ongoing audit.

Adolescent↗
PubMed1999

Design, synthesis, and evaluation of chromen-2-ones as potent and selective human dopamine D4 antagonists.

The discovery of a series of chromen-2-ones with selective affinity for the dopamine (DA) D4 receptor is described. Target compounds were tested for binding to cloned human DA D2L, D3, and D4.2 receptor subtypes expressed in Chinese hamster ovary K1 cells. Several compounds demonstrated high affinity (<20 nM, K(i)) and greater than 100-fold selectivity for DA D4.2 versus DA D2L receptors. The results of a SAR study are discussed within. In a DA D4 functional assay measuring [(3)H]thymidine uptake, target compounds showed antagonist activity at the D4.2 receptor. Compound 22, 7-[(2-phenylaminoethylamino)methyl]chromen-2-one, increased DOPA (L-3,4-dihydroxyphenylalanine) accumulation 51% in the hippocampus and 23% in the striatum of rat brains when dosed orally at 20 mg/kg.

Animals↗
PubMed1999

Prevalence of Ras mutations in thyroid neoplasia.

OBJECTIVE: Mutations at codons 12, 13 or 61 of ras which result in constitutive activation occur frequently in human malignancies. There have been varied reports on their prevalence and hence their likely significance in the pathogenesis of primary thyroid neoplasia. To address this, we have examined a large series of benign and malignant thyroid tumours for ras mutations. DESIGN: Genomic DNA was analysed for the presence of mutations at codons 12, 13 and 61 of H-ras, K-ras and N-ras by allele-specific oligonucleotide hybridization. Direct DNA sequencing was used to confirm the mutations. PATIENTS: A total of 90 samples with benign (66) and malignant (24) thyroid disease were investigated. RESULTS: A total of 14/90 (15.5%) samples had a ras mutation. All mutations were at codon 61 of either N-ras or K-ras. The positive cases were 1/25 (4%) nodular goitre, 7/38 (18%) follicular adenoma, 4/9 (44%) follicular carcinoma, 1/1 anaplastic carcinoma, 1/1 follicular variant of papillary carcinoma, and 1 metastatic follicular carcinoma in which the primary tumour had the same mutation. CONCLUSIONS: Our data demonstrate a relatively low overall prevalence of ras mutations in thyroid neoplasia, with a predominance in follicular neoplasms. Their presence in follicular adenomas suggests that they may have an early aetiological role in the development of thyroid neoplasia.

Adenocarcinoma, Follicular↗
PubMed1999

Injury hospitalizations among American Indian youth in Washington.

OBJECTIVE: To determine the rate and causes of hospitalizations for injury among American Indian and Alaska Native (AI/AN) youth in the state of Washington, and to compare this with the rate of hospitalizations for injury among youth of all races. METHODS: Subjects were aged 0-19 years and were admitted to civilian hospitals for care of an injury (International Classification of Diseases N codes 800-995) in Washington between 1990 and 1994. Deaths occurring in the prehospital setting and emergency department are not included. Using several fields of identifying information, the Washington state hospital discharge database was linked with the Indian Health Service (IHS) patient registration database to identify AI/AN youth. Denominator data included the total age specific IHS user population for American Indians and US Census derived population estimates. Incidence ratios (IRs) were calculated to compare rates of hospitalization between AI/AN youth and all youth in Washington. RESULTS: A total of 694 and 29,048 hospitalizations for injury were identified for AI/AN youth and all races, respectively. The rate of hospitalization for injuries among AI/AN youth was 507 discharges per 100,000 youth (IR = 1.30; 95% confidence interval (CI) 1.20 to 1.40. The leading mechanism of injury was motor vehicles (IR 1.73, CI 1.49 to 2.01), followed by falls (IR 0.95, CI 0.79 to 1.15), and poisoning (IR 1.20, CI 0.80 to 1.78). The disparity was greater for intentional injuries (IR 1.71, CI 1.44 to 2.04). The highest IR for all unintentional injuries was for injuries from fire (IR 2.35, CI 1.42 to 3.87). AI/AN children aged 15-19 had the greatest disparity for rates of injury hospitalization (IR 1.4, CI 1.25 to 1.56). CONCLUSION: AI/AN youth in Washington had a higher hospitalization rate for injury compared with all youth in the state. Disparities were greatest for injuries related to motor vehicles and assaults. When linked, hospital discharge data can be used for surveillance of AI/AN hospitalizations.

Adolescent↗
PubMed1999

KU activity.

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England↗
PubMed1999

Identification and analysis of homoeologous segments of the genomes of rice and Arabidopsis thaliana.

Using contiguous genomic DNA sequences of Arabidopsis thaliana, we were able to identify a region of conserved structure in the genome of rice. The conserved, and presumptive homoeologous segments, are 194 kb and 219-300 kb in size in Arabidopsis and rice, respectively. They contain five homologous genes, distinguished in order by a single inversion. These represent the first homoeologous segments identified in the genomes of a dicot and a monocot, demonstrating that fine-scale conservation of genome structure exists and is detectable across this major divide in the angiosperms. The conserved framework of genes identified is interspersed with non-conserved genes, indicating that mechanisms beyond segmental inversions and translocations need to be invoked to fully explain plant genome evolution, and that the benefits of comparative genomics over such large taxonomic distances may be limited.

Arabidopsis↗
PubMed1998

Macrophage and hepatic stellate cell responses during experimental hepatocarcinogenesis.

The aim of the study was to assess the monocyte/macrophage and hepatic stellate cell responses during experimental diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Diethylnitrosamine (50mg/L) was administered to 39 rats for 10 weeks; liver tissue was obtained at weeks 10, 16 and 19. In this model, necroinflammatory damage occurs during the period of DEN administration but thereafter subsides; dysplastic nodules and carcinomas subsequently develop. Monocytes/ macrophages were detected immunohistochemically using ED1 and ED2 monoclonal antibodies; hepatic stellate cells (HSC) were detected using antibodies to alpha-smooth muscle actin (alpha-SMA) (activated HSC) and glial fibrillary acidic protein (GFAP). Parenchymal ED1- and ED2-positive monocytes/macrophages and alpha-SMA-positive HSC increased at week 10 when there was ongoing DEN-induced necroinflammatory activity. ED1- and ED2-positive cells were also prominent at weeks 16 and 19, particularly around the periphery of dysplastic and carcinomatous nodules, with occasional macrophages between dysplastic hepatocytes. alpha-SMA-positive HSC were present within sinusoids between dysplastic cells and were more abundant at weeks 16 and 19 than in control or week 10 animals. Activated HSC were prominent in fibrous septa around and within dysplastic and carcinomatous nodules at weeks 16 and 19. In contrast, GFAP-positive HSC did not accumulate in developing septa or within dysplastic and carcinomatous nodules. We have demonstrated changes in the monocyte/ macrophage and HSC populations during the development of hepatocellular dysplasia and carcinoma at time points when there is little necroinflammatory activity; this may therefore represent a host response to hepatocyte dysplasia. The HSC activation may be mediated, in part, by monocyte/ macrophage-derived factors, but we speculate that it may also result from direct stimulation by factors released from dysplastic hepatocytes.

Actins↗
PubMed1998

Myxoglobulosis, a rare variant of appendiceal mucocele, occurring secondary to an occlusive membrane.

A 77-year-old man presented with altered bowel habit and episodic right lower abdominal discomfort. A barium enema showed a large smooth filling defect in the caecum and at operation his appendix was seen to be hugely distended. Pathological examination showed myxoglobulosis, a rare variant of mucocele of the appendix. The appendiceal orifice was completely occluded by an imperforate membrane with no communication between the appendix and caecum. This is the first published report in the English language of appendiceal myxoglobulosis in association with such an occlusive membrane.

Abdominal Pain↗
PubMed1997

Association between risk of seroconversion of sentinel cattle to bluetongue viruses and Culicoides species (Diptera: Ceratopogonidae) in Queensland, Australia.

The association between risk of seroconversion of sentinel cattle to bluetongue viruses and the number of Culicoides brevitarsis Kieffer and C. wadai Kitaoka caught by light traps was investigated using survival analysis. Eight sentinel herds that seroconverted to bluetongue viruses between 1990 and 1994, and for which insect-trapping data were available, were selected for inclusion in the study. These herds were located at six sites along the eastern coast of Queensland, Australia, from approximately latitude 10 degrees South to 25 degrees South. C. brevitarsis was detected at all locations where sentinel herds were maintained, whereas C. wadai was detected at only two locations in northern Queensland where four sentinel herds were maintained during the study period. The mean number of C. brevitarsis and C. wadai caught per month was 230 and 21, respectively. A significant (P = 0.05) positive association was found between the risk of seroconversion of sentinel cattle to bluetongue viruses and the number of C. wadai caught in the same month.

Animals↗
PubMed1997

PCR ribotyping and endonuclease subtyping in the epidemiology of Burkholderia cepacia infection.

Because of conflicting data about hospital-based transmission of Burkholderia (Pseudomonas) cepacia, an important respiratory pathogen in cystic fibrosis (CF), we compared strains found in sputum, lung, or blood of 29 CF patients in our center from 1988 to 1994, studying the relationship between strain and hospital exposure of incident and that of prevalent cases. Exposure was defined as a concurrent hospital stay between a prevalent and an incident case. B. cepacia strains were determined by polymerase chain reaction (PCR) ribotyping and endonuclease subtyping. The 16S to 23S spacer regions of the bacterial ribosomal RNA (rRNA) genes were amplified by PCR, and the product-size patterns used to type each B. cepacia isolate. Endonuclease digestion of the PCR products provided length polymorphisms for subtyping. There were 17 incident events during the period from 1988 to 1994, 16 of which involved a single ribotype. These 16 ribotypes could be divided into five subtypes by endonuclease mapping. Four patients grew B. cepacia from the blood, with the organism being the same strain as found in the lung in each case. Case controls were obtained to evaluate risk factors for B. cepacia acquisition. Concurrent hospitalization with a prevalent case significantly increased the risk of acquisition. There was no association between length of hospitalization, length of exposure, or FEV1 and the risk of B. cepacia acquisition.

Adolescent↗
PubMed1996

Spatial analysis of seroconversion of sentinel cattle to bluetongue viruses in Queensland.

OBJECTIVE: To assess quantitatively the spatial distribution of seroconversion of Queensland cattle to bluetongue viruses. DESIGN: A sentinel herd study. SAMPLE POPULATION: Sixty-nine sentinel herds at 30 locations. PROCEDURE: Spatial clustering of seroconversion to bluetongue viruses was investigated during the period from 1990 to 1994. RESULTS: Seroconversion to only two bluetongue virus serotypes, 1 and 21, was observed. The 14 herds, in which seroconversion to bluetongue virus serotype 1 was detected, were located only along the eastern coastal and subcoastal region of Queensland, and were significantly (P < 0.05) clustered. Locations at which seroconversion to serotype 21 was detected, were not significantly clustered. The results generally agree with field observations, except for the failure to detect seroconversion to bluetongue viruses in north-western Queensland. CONCLUSION: Bluetongue infection of cattle in north-western Queensland may be temporally sporadic. The dominance of serotype 1 in the Queensland cattle population may be the result of differential transmission by potential vector species. Long-term surveillance programs are important for defining disease status of animal populations.

Animals↗
PubMed1996

Hepatitis C virus: epidemiology and genotypes in the north east of England.

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p < 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p < 0.01, acinar activity: p < 0.001, fibrosis: p < 0.0001). Liver disease worsened with increased duration of infection (p < 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p < 0.05, hepatocellular carcinoma, p < 0.02).

Adult↗