Characterisation of group A streptococci from necrotising fasciitis cases in Gloucestershire, United Kingdom.
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Biomedical subjects
Publications and source records attributed to M Upton.
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BACKGROUND & AIMS: Helicobacter pylori adheres to gastric epithelial cells and stimulates interleukin (IL)-8 production. This may be instrumental in neutrophil infiltration of the gastric epithelium that characterizes H. pylori gastritis. This study examined the molecular mechanisms leading to H. pylori-induced epithelial cell IL-8 production. METHODS: Electrophoretic mobility shift analyses for NF-kappa B were performed on cell and nuclear extracts from H. pylori-infected AGS and Kato III human gastric epithelial cells. RESULTS: H. pylori infection activated the transcription factor NF-kappa B and induced nuclear translocation of both NF-kappa B p50/p65 heterodimers and p50 homodimers. Nuclear translocation of NF-kappa B (30 minutes) was followed by increased IL-8 messenger RNA (1 hour) and protein levels (4 hours) consistent with NF-kappa B up-regulation of IL-8 gene transcription. Pretreatment of AGS cells with PDTC, which blocks NF-kappa B activation, inhibited H. pylori-induced increases in IL-8 production by 90%. Immunohistochemical studies using a monoclonal antibody that recognizes the I-kappa B binding region of p65 showed activated NF-kappa B in gastric epithelial cells of patients with H. pylori gastritis. CONCLUSIONS: H. pylori infection activates NF-kappa B in gastric epithelial cells in vitro and in vivo. NF-kappa B is a transcriptional regulator of IL-8 production, and its activation after bacterial infection may be an important defense response in gastrointestinal epithelial cells.
We present the pathology and molecular genetic analysis of an infant with congenital myotonic dystrophy. The proband/infant, born at 35 weeks' gestational age to a mother with myotonic dystrophy and 750 CTG repeats, was markedly hypotonic and had severe cardiomyopathy. She died after 16 days of life. At autopsy, skeletal and heart muscles were immature and had a decrease in contractile elements. DNA CTG trinucleotide repeat analysis of the proband demonstrated 2,480 repeats in blood and a slightly greater number of repeats in skeletal muscles, viscera, and gray matter. Corresponding to the clinical course and pathology, cardiac tissues displayed somatic mosaicism, with repeats ranging from 2,760 to 3,220.
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To evaluate ThinPrep (Cytyc, Marlborough, MA) processing of endoscopic brushing specimens for cytologic examination, ThinPrep slides and direct smears of 29 gastrointestinal (GI) and 22 bronchial brushings were compared. Clinicians prepared the direct smears. The brush was then immersed in CytoLyt (Cytyc) and one ThinPrep slide made. All cases had corresponding biopsies. Smears and ThinPrep slides were screened and reviewed independently. Screening time per case was recorded. All slides were evaluated for cellularity, quality, cellular preservation, and quantity of diagnostic cells. A diagnosis was rendered for each case. Cytologic and histologic diagnoses were correlated. Follow up was obtained for cases with discrepant histologic and cytologic diagnosis. Twenty-three brushings were from esophagus, 5 stomach, 1 duodenum, and 22 lung. An average of 3.6 direct smears (range 2-6) was made for each case. Average screening time per case was 12 minutes for GI direct smear, 15 minutes bronchial direct smear, 4 minutes GI ThinPrep slide, and 9 minutes bronchial ThinPrep slide. ThinPrep slides were superior to direct smears in cellularity, quantity of diagnostic cells, and quality of slides. ThinPrep slides and direct smears showed comparable cellular preservation. The sensitivity of detecting malignancy by biopsy, direct smears, and ThinPrep slides was 81%, 75%, and 75%, respectively. One false-positive diagnosis was made on cytology with both direct smear and ThinPrep slide, a case with radiation atypia. In conclusion, ThinPrep slides are at least comparable to direct smears in cytologic examination of brushings. However, false-positive diagnosis is a possible potential pitfall.
To explain the worldwide increase in the frequency of severe infections by group A streptococci, molecular techniques are increasingly being employed to evaluate the genetic relationships of strains. We used restriction endonuclease analysis, pulsed-field gel electrophoresis (PFGE), the PCR, ribotyping, and DNA sequence analysis in a study of 13 group A streptococci isolated from a cluster of cases of serious infections over a 3-month period in Tayside, Scotland. Eight of the strains were M type 3; molecular characterization identified two subclones. The first, displaying PFGE profile 4, has been observed in Northern Scotland and has been circulating in New Zealand for over a decade. The second subclone has been documented only in the United Kingdom; it was first seen in 1993 in Scotland. Sequence analysis of emm-3 genes further differentiated the PFGE 4 subclone. DNA sequence analysis of virulence factors supports the suggestion that they may have recently been acquired by horizontal gene transfer.
PURPOSE: Although acute lymphoblastic leukemia may masquerade as hypopyon uveitis, acute myeloid leukemia has only rarely been reported to cause this complication, and ocular relapse generally has been associated with evidence of malignant cells at other sites. We studied a patient with acute myeloid leukemia whose only sign of relapse was bilateral anterior uveitis with pseudohypopyon that was refractory to topical and systemic corticosteroids. METHODS: A 26-year-old woman with acute myeloid leukemia in remission, who had bilateral anterior uveitis and increased intraocular pressure at initial examination, was studied clinically. Blood films, bone marrow smears, and preparations were examined by using immunoperoxidase staining. RESULTS: Although there was no evidence of leukemia in the blood or bone marrow samples, the cells obtained from the anterior chamber showed myeloblastic leukemic cells with morphologic characteristics similar to those present in the original bone marrow biopsy obtained 14 months previously. Irradiation and chemotherapy were used to kill the malignant cells in the eye and central nervous system. The persisting glaucoma resolved after anterior chamber washout of necrotic tumor cells. CONCLUSIONS: Unusual features of uveitis in this patient indicated that she had a masquerade syndrome, despite normal results of bone marrow and blood film tests. Aspiration of intraocular cellular infiltrate for cytopathologic examination was required to obtain the correct diagnosis and enable treatment to commence without delay.
We have used molecular techniques to characterize 51 group A streptococci from Scotland and 17 'serious disease' isolates from other countries, in order to establish the clonal structure of invasive Streptococcus pyogenes strains circulating between 1986 and 1993. Strains were grouped by restriction endonuclease analysis, pulsed field gel electrophoresis and ribotyping patterns, and were examined for the presence of alleles of the speA gene by polymerase chain reaction and DNA sequence analysis. Serious and fatal infections in Scotland were caused by several clones. One clone (9 of 51 strains) was M type 1 and possessed the speA gene allele 2. This was the clone previously identified as causing severe infection in the USA. Another clone (5 of 51 strains) was M type 3 and had speA gene allele 3. In view of the clear association of more than one clone with severe, invasive and fatal infections, horizontal gene exchange between genotypes merits further investigation.
BACKGROUND: Inadvertent sampling of normal thyroid tissue surrounding a nodule may occur when clinically inexperienced personnel perform fine-needle aspiration (FNA) or when a nodule is small. Because the cytologic characteristics of normal thyroid tissue are not well known, we prospectively studied 42 patients undergoing thyroidectomy. METHODS: FNA was performed from the grossly normal contralateral lobe during thyroidectomy. Cytopathologists examined the slides without knowing the source of the tissue. RESULTS: FNA of grossly normal thyroid tissue was adequate for interpretation in 32 of 42 patients, and in nine of 42 cases it was interpreted as unremarkable. However, the remaining specimens were classified as microfollicular lesions (18), mixed macromicrofollicular lesions (three), Hürthle cell lesion (one), and papillary thyroid carcinoma (one). CONCLUSIONS: FNA of grossly normal thyroid tissue suggested a microfollicular lesion in 18 (56%) patients, a result that would raise the possibility of a follicular carcinoma and often lead to the recommendation for operation. When FNA is performed, normal thyroid tissue surrounding a nodule should be avoided, and the possibility of a sampling error should be considered when a microfollicular pattern is obtained in a patient with a small nodule.
Although world average food production per person is increasing there are many countries, particularly in sub-Saharan Africa, where production has fallen in recent decades. The economic analysis of the world food problem concerns the dynamics of production, income, growth, demand and trade. The 'law of diminishing returns' suggests that labour incomes fall as population density increases. Capital investment and technological change, particularly with a land-saving bias, can overcome this effect. Such land-saving innovations are less appropriate where population densities are lower, as in much of sub-Saharan Africa. Innovations which reduce risk, such as stress- and disease-resistant crop varieties, may be more attractive to farmers. Communal or government action is required to ensure sustainability of food production; to reduce risk, through price stabilization, possibly crop insurance and contingency plans for famine relief; to promote equity and to ensure competitive market conditions. Public funding of agricultural research is necessary to promote growth in food supplies. If increases in supply do not keep pace with growth in demand, food prices rise, attracting resources into food production. If supply grows faster, food prices and farm incomes fall, driving resources out of agriculture. Resources may not move fast enough to correct imbalances. Primary producers are likely to face deteriorating terms of trade. Linkages between food production and other sectors are weak, so primary exports are not a good basis for economic development. Import substitution strategies may damage agriculture. Structural adjustment regimes have been adopted in some countries to correct imbalances and provide an incentive for farmers to increase production. Associated reductions in public expenditure may have a contrary impact.
The pathogenesis of esophageal squamous papilloma is not known, but chronic mucosal irritation and infection with human papillomavirus are two proposed etiologies. To investigate these hypotheses, we analyzed the clinical data and histological features of 38 esophageal squamous papillomas from 33 patients and performed the polymerase chain reaction technique for detection of several common human papilloma virus types on a subset of cases (n = 26) with sufficient available material. Clinically, males were affected more often than females (M:F ratio = 24:9); average age was 50 (range, 2-86 years). Most papillomas occurred singly (85%) and were located in the distal esophagus (70%). Patients with esophageal squamous papillomas, especially those with lesions in the distal esophagus, commonly had an associated chronic and often severe form of esophageal mucosal irritation such as esophagitis or Barrett's esophagus. Esophageal squamous papillomas were small polyps (average size, 0.5 cm) that we classified histologically into three types (exophytic, 50%; endophytic, 37%; spiked, 13%) based on the predominant shape of the squamous papillae. Fifty percent of the papillomas (13 of 26) tested, from 57% of patients (12 of 21), were positive for human papilloma virus, most commonly type 16 (nine of 13), less often type 16 and 18 together (3/13), and rarely type 6b/11 (1 of 13). We propose a multifactorial etiology in which the synergistic action of mucosal irritation and human papilloma virus may be necessary for the development of esophageal squamous papillomas.
Many literature reports have cited the importance of the rehydration conditions of lyophilized cultures in determining viability. The rate of rehydration and the volume of fluid used have been identified as two important factors. One possible means of controlling these is by immobilizing the cells before lyophilization within a gel matrix in which the subsequent rehydration rate and fluid volume would be controlled by the properties of the gel. In this study Lactobacillus plantarum was immobilized and lyophilized in Ca-alginate beads in which 1 M glycerol or 0.75 M adonitol with skim milk were incorporated as a cryoprotectant. The properties of these Ca-alginate beads were examined before and after lyophilization and rehydration. The beads incorporating glycerol were smaller and stronger than those with adonitol. After lyophilization, size decreased and strength increased but to a greater extent in the beads with glycerol, indicating that the microenvironment within the two bead types was probably different. The protective effect of the bead microenvironment on immobilized L. plantarum was also examined. Lyophilization and rehydration within the alginate beads with either polyol yielded higher survival rates than that attained with free cell cultures during rehydration in optimal or suboptimal conditions. During rehydration under suboptimal conditions, the immobilized cell survival was greatest when 0.75 M adonitol was the incorporated cryoprotectant.
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In 150 middle-aged men prone to coronary disease, long-term data based on the Chicago Coronary Prevention Evaluation Program's diet showed that there was a favorable effect on fasting glycemia level and glucose tolerance. This diet for reducing obesity and hypercholesterolemia was low in cholesterol and saturated fat and moderate in polyunsaturated and total fat, with replacement of some fat by carbohydrate. At 2 years, decreased weight and serum cholesterol values of normoglycemic men were accompanied by a modest but significant fall in fasting and postload glycemia; at 4 years. fasting glycemia levels remained slightly below baseline. For men with suspect fasting hyperglycemia at baseline, sustained fall in weight and serum cholesterol value was associated with sizeable long-term reductions in fasting glycemia and improvement of glucose tolerance. Decrease in plasma glucose was significantly related to decrease in weight. No evidence of impairment of glucose tolerance with years-long consumption of this diet was recorded.
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