Axillary sinuses and cervical swellings.
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Biomedical subjects
Publications and source records attributed to E Higgins.
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A 28-year-old man, on immunosuppressive therapy for a recent kidney-pancreas transplant, presented to our department with an unusual violaceous nodule on his right knee. A biopsy specimen showed a granulomatous response in the dermis, surrounding numerous fungal cells and septate hyphae. Fungal cultures yielded dark grey colonies, which were identified as Alternaria tenuissima. To our knowledge this is the first report of A. tenuissima infection reported in the U.K.
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Summary Immune reconstitution is a well recognized phenomenon associated with the use of highly active antiretroviral therapy (HAART) for HIV infection. After the administration of HAART there is a rise in CD4 T-cell count in the circulation brought about by cessation of HIV replication. This allows the body to respond to antigens that it previously ignored. This manifests itself most commonly as an overt illness to previously ignored pre-existing infections such as Mycobacterium tuberculosis, herpes simplex virus, varicella zoster virus, hepatitis B and C viruses, cytomegalovirus, cryptococcal infection, human papilloma virus and molluscum contagiosum. There are further reports of reactions to sarcoid and tattoo pigment and one previous case reported of a granulomatous reaction to a foreign body. We report another case of a foreign body granuloma reaction, to tribal medicine implanted in tribal marks made in childhood in a Zimbabwean woman. This reaction is part of the immune reconstitution syndrome.
BACKGROUND: S100 protein is an acidic calcium binding protein that is expressed by melanoma cells. Elevated serum values of S100 have been described in metastatic disease and it has been suggested that it may be used as an adjunct to staging and monitoring of treatment. Micrometastatic disease in the sentinel lymph node can be demonstrated by sentinel node biopsy (SNB) and the sentinel node status is known to be the most important predictor of relapse. OBJECTIVES: To determine whether serum S100 concentrations could predict the presence of micrometastatic disease. METHODS: Thirty-one patients with primary cutaneous melanoma > 1 mm were recruited from referrals to the Melanoma clinic. All patients had serum S100 concentrations evaluated prior to undergoing SNB. Serum S100 concentrations were established using an immunoluminometric method. Sentinel nodes were identified using a dual technique with both radiolabelled colloid (residual from preoperative lymphoscintigraphy) and blue dye according to the MD Anderson Cancer Center protocol. Results Nine of these 31 patients had evidence of micrometastatic disease on SNB. The mean serum S100 concentration of those with positive SNBs was 0.027 microg L-1 compared with 0.045 microg x L(-1) in patients with negative SNBs (normal < 0.14 microg x L(-1)). No patient in the study demonstrated raised concentrations of serum S100. CONCLUSIONS: We conclude that serum S100 concentrations do not predict the presence of micrometastatic melanoma in sentinel nodes in primary cutaneous melanoma.
PURPOSE: Sentinel node biopsy (SNB) is a surgical technique for detecting micrometastatic disease in the regional draining nodes. 2-fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning is an imaging technique that can detect clinically undetectable metastases. This prospective study was undertaken to compare the sensitivity of FDG-PET scanning with SNB in the detection of micromatastatic malignant melanoma. PATIENTS AND METHODS: Fifty consecutive patients (23 women, 27 men; mean age, 53 years) with primary melanoma >1 mm thick or lymphatic invasion were recruited (mean, 2.41 mm). Primary lesions had been narrowly excised (<1 cm). Patients underwent PET scanning followed by SNB, using a dual technique. Preoperative lymphoscintigraphy was used to identify the draining basin. Lymph nodes were examined histologically and immunostained for S100 and HMB 45. RESULTS: The sentinel node (SN) was identified in all patients. Fourteen patients (28%) had positive SNBs, including eight patients with melanoma <1.5 mm thick. In none of these 14 patients did PET scans identify metastatic disease in the SN or draining basin. In seven patients, the PET scans were positive in other locations, and in four cases, this was suspicious of metastatic disease. However, no patient has developed recurrent melanoma (mean follow-up, 15 months). All patients with positive SNBs underwent therapeutic lymph node dissection. Further lymph node involvement was found in two patients (primary lesions, 1.3 mm and 3.5 mm thick). CONCLUSION: This study demonstrates the limitations of FDG-PET scanning in staging patients with primary melanoma. SNB is the only reliable method for identifying micrometastatic disease in the regional draining node.
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Initial anecdotal evidence that both smoking and drinking have an influence on psoriasis have been borne out in more detailed epidemiological studies. However, there appears to be some geographical variation between populations and a marked gender bias. The possibility that simple modifications in lifestyle may reduce both the prevalence and severity of psoriasis offers an exciting potential adjunct to treatment in the future.
Recombinant human antithrombin (rhAT) produced in transgenic goat milk was purified to greater than 99%. The specific activity of the rhAT was identical to human plasma-derived AT (phAT) in an in vitro thrombin inhibition assay. However, rhAT had a fourfold higher affinity for heparin than phAT. The rhAT was analyzed and compared with phAT by reverse phase high-performance liquid chromatography, circular dichroism, fluorophore-assisted carbohydrate electrophoresis (FACE), amino acid sequence, and liquid chromatography/mass spectrography peptide mapping. Based on these analyses, rhAT was determined to be structurally identical to phAT except for differences in glycosylation. Oligomannose structures were found on the Asn 155 site of the transgenic protein, whereas only complex structures were observed on the plasma protein. RhAT contained a GalNAc for galactose substitution on some N-linked oligosaccharides, as well as a high degree of fucosylation. RhAT was less sialylated than phAT and contained both N-acetylneuraminic and N-glycolylneuraminic acid. We postulate that the increase in affinity for heparin found with rhAT resulted from the presence of oligomannose-type structures on the Asn 155 glycosylation site and differences in sialylation.
Tuberous sclerosis complex (TSC) is a dominantly inherited multisystem disorder resulting in the development of hamartomatous growths in many organs. Genetic heterogeneity has been demonstrated linking the familial cases to either TSC1 at 9q34.3, or TSC2 at 16p13.3. About two-thirds of the TSC cases are sporadic and appear to represent new mutations. While both genes are thought to account for all familial cases, with each representing approximately 50% of the mutations, the proportion of sporadic cases with mutations in TSC1 and TSC2 is yet to be determined. We have examined the entire coding sequence of the TSC2 gene in 20 familial and 20 sporadic cases and identified a total of twenty-one mutations representing 50% and 55% of familial and sporadic cases respectively. Our rate of mutation detection is significantly higher than other published reports. Twenty out of 21 mutations are novel and include 6 missense, 6 nonsense, 5 frameshifts, 2 splice alterations, a 34 bp deletion resulting in abnormal splicing, and an 18 bp deletion which maintains the reading frame. The mutations are distributed throughout the coding sequence with no specific hot spots. There is no apparent correlation between mutation type and clinical severity of the disease. Our results document that at least 50% of sporadic cases arise from mutations in the TSC2 gene. The location of the mutations described here, particularly the missense events, should be valuable for further functional analysis of this tumor suppressor protein.
We have used a new technique of bleomycin injection to treat intractable palmar, plantar and periungual warts. Following local anaesthesia with topical EMLA (lignocaine and prilocaine) cream, 1 mg/ml bleomycin solution was dropped on to the wart and 'pricked' into the wart using a Monolet needle. We achieved 92% success rate which compares well with other authors whose success rates with intralesional bleomycin vary between 33 and 92%. We conclude that this technique of intralesional bleomycin therapy is an effective, safe and generally well tolerated treatment for recalcitrant warts.
A full length cDNA clone encoding rose dihydroflavonol 4-reductase (DFR) was isolated from a cDNA library derived from rose petals by screening with the cDNA of Petunia hybrida DFR. Sequence comparison of the rose DFR with reported DFR genes revealed that they are homologous to each other. The amount of DFR mRNA in rose petals was developmentally regulated and paralleled anthocyanin production in petals. Sepals, thorns, styles and stamens also contained anthocyanins and DFR mRNA. No DFR mRNA was observed in mature leaves and a small amount of the transcript was detected in young leaves. A petunia cultivar, whose colour was pale pink due to a deficiency in flavonoid 3'-hydroxylase and flavonoid 3',5'-hydroxylase, was transformed with a binary vector containing a rose DFR cDNA cloned behind a constitutive promoter. Petals and anthers of the resultant transgenic petunia plants were salmon pink and contained pelargonidin, an anthocyanidin rarely found in petunia.
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Malignant transformation of rodent cell lines by polyoma virus and by activated ras genes is associated with increased UDP-GlcNAc:Man alpha-R beta-1,6-N-acetylglucosaminyltransferase V (GlcNAc-transferase V) activity and it product -GlcNAc beta 1-6Man alpha 1-6Man beta 1-branched Asn-linked oligosaccharides. In this report, we have compared beta 1-6GlcNAc branching of core O- and N-linked oligosaccharides in three experimental models of malignancy, namely (a) rat2 fibroblasts and their malignant T24H-ras-transfected counterpart; (b) benign SP1 mammary carcinoma cells and two metastic sublines of SP1; and (c) the metastatic MDAY-D2 lymphoma cell line and its poorly metastatic glycosylation mutant KBL-1. In addition to the previously reported increase in GlcNAc-transferase V activity, UDP-GlcNAc:Gal beta 1-3GalNAc alpha-R (GlcNAc to GalNAc) beta-1,6-N-acetylglucosaminyltransferase (core 2 GlcNAc-transferase, EC 2.4.1.102) activity was found to be elevated by 70% in the malignant rat2 and SP1 cell lines while several other glycosyltransferase activities were not significantly different. The action of core 2 GlcNAc-transferase followed by beta 1-4Gal-transferase provides an N-acetyllactosamine antenna that can be extended with polylactosamine (i.e. repeating Gal beta 1-4GlcNAc beta 1-3) provided UDP-GlcNAc:Gal beta-R beta 1-3GlcNAc-transferase (GlcNAc-transferase) (i)) activity is present. Polylactosamine content in microsomal membrane glycoproteins was quantitated by labeling the GlcNAc termini resulting from the action of Escherichia freundii endo-beta-galactosidase with bovine galactosyltransferase/UDP-[3H] Gal. Glycopeptidase F- sensitive and -insensitive fractions were measured to assess the N- and O-linked components. In the SP1 tumor model, the metastatic sublines showed increased core 2 GlcNAc-transferase and GlcNAc-transferase V activities but no change in GlcNAc-transferase (i) activity, yet polylactosamine was increased in both O- and N-linked oligosaccharides. In rat2 cells, down-regulation of GlcNAc-transferase (i) following transformation was associated with decreased polyactosamine even though core 2 GlcNAc-transferase and GlcNAc-transferase V were elevated in the cells. Finally, a 3-fold decrease in GlcNAc-transferase V in KBL-1, the glycosylation mutant of MDAY-D2 cells, resulted in complete loss of polylactosamine in N-linked but no change in O-linked polylactosamine content. These results suggest that, provided GlcNAc-transferase (i) is not limiting, the beta 1-6-branching enzymes core 2 GlcNAc-transferase and GlcNAc-transferase V regulate the levels of polyactosamine in O- and N-linked oligosaccharides, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Aryl-N-acetyl-alpha-galactosaminides (aryl-GalNAc) are acceptor substrates for UDP-Gal:alpha-GalNAc beta 1-3 galactosyltransferase and, in vivo, aryl-GalNAc have been shown to inhibit O-linked oligosaccharide biosynthesis (Kuan et al., J. Biol. Chem. 264, 19271, 1989). Since aryl-GalNAc, appears to enter viable cells and serve as an acceptor for O-glycosylation enzymes, the recovery and characterization of the aryl-oligosaccharides from cell culture medium may reflect cellular pattems of O-glycosylation. To pursue this possibility, the following paranitrophenyl-linked oligosaccharide standards were enzymatically synthesized and characterized by 1H-NMR: Gal beta 1-3(GlcNAc beta 1-6)Gal-NAc alpha-pNp; Gal beta 1-3(Gal beta 1-4GlcNAc beta 1-6)GalNAc alpha-pNp; SA alpha 2-3Gal beta 1-3(SA alpha 2-3Gal beta 1-4GlcNAc,beta 1-6)GalNAc alpha-pNp; SA alpha 2-3Gal beta 1-3GalNAc alpha-pNp. As a model system, MDAY-D2 lymphoid tumour cells were cultured for various periods in medium containing 2 mM GalNAc alpha-pNp. The secreted aryl-oligosaccharides were separated by Biogel P2 chromatography and DEAE HPLC, followed by further fractionation of the disialyl oligosaccharides on an Ultrahydrogel HPLC column. Absorbance of the paranitrophenyl aryl constituent at 303 nm allowed detection at the 10 pmol level and provided a relatively specific means of following the oligosaccharides. MDAY-D2 cells produced disialylated aryl-oligosaccharides at a rate of 20 pmol/h/10(6) cells with a half-time of transit to the cell surface of 13.6 min, a rate consistent with their movement from the Golgi to the cell surface by bulk flow.(ABSTRACT TRUNCATED AT 250 WORDS)