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Michael Wells

Publications and source records attributed to Michael Wells.

15 recordsLinked to original sources
PubMed2024

Ammonia-oxidizing bacteria and archaea exhibit differential nitrogen source preferences.

Ammonia-oxidizing microorganisms (AOM) contribute to one of the largest nitrogen fluxes in the global nitrogen budget. Four distinct lineages of AOM: ammonia-oxidizing archaea (AOA), beta- and gamma-proteobacterial ammonia-oxidizing bacteria (β-AOB and γ-AOB) and complete ammonia oxidizers (comammox), are thought to compete for ammonia as their primary nitrogen substrate. In addition, many AOM species can utilize urea as an alternative energy and nitrogen source through hydrolysis to ammonia. How the coordination of ammonia and urea metabolism in AOM influences their ecology remains poorly understood. Here we use stable isotope tracing, kinetics and transcriptomics experiments to show that representatives of the AOM lineages employ distinct regulatory strategies for ammonia or urea utilization, thereby minimizing direct substrate competition. The tested AOA and comammox species preferentially used ammonia over urea, while β-AOB favoured urea utilization, repressed ammonia transport in the presence of urea and showed higher affinity for urea than for ammonia. Characterized γ-AOB co-utilized both substrates. These results reveal contrasting niche adaptation and coexistence patterns among the major AOM lineages.

Archaea↗
PubMed2006

A study of luteal phase expression of inhibin, activin, and follistatin subunits in the endometrium of women with recurrent miscarriage.

OBJECTIVE: To compare the luteal phase endometrial expression of inhibin, activin, and follistatin subunits in women with recurrent miscarriage compared to a control group. Other parameters of luteal function assessed included Doppler blood flow, serum biochemical markers, and histopathology. DESIGN: This was a prospective case control study. SETTING: The study was conducted in a tertiary care hospital of Sheffield, United Kingdom. PATIENT(S): Thirty-three women with recurrent miscarriage and 10 women with no previous history of miscarriage (control group) were recruited. INTERVENTION(S): Histologic assessment of the luteal phase endometrium was done using Noyes criteria followed by immunohistochemical analysis for expression of inhibin, activin, and follistatin subunits. Doppler analysis for perifollicular and endometrial blood flow was also done. Simultaneously serum concentrations of E(2), LH, FSH, P, and inhibin B at the time of LH surge and at LH +7 days were measured. MAIN OUTCOME MEASURES: Difference in endometrial expression of inhibin, activin, and follistatin subunit in the two groups. RESULT(S): Endometrial expression of follistatin and beta A in the endometrial stromal cells of women with recurrent miscarriage was significantly lower than in control women. There were no differences in results of the Doppler studies or the hormonal profiles between cases and controls. CONCLUSION(S): The lower expression of follistatin and beta A subunit in women with recurrent miscarriage may imply an altered activity of activin A at the time of decidualization, which may lead to poor pregnancy outcome in the form of miscarriage.

Abortion, Habitual↗
PubMed2006

John H. Law.

Explore the source record for details and available documents.

Biochemistry↗
PubMed2006

Bullous reaction to topical methchlorethamine in mycosis fungoides.

We describe a patient with mycosis fungoides who developed a bulla shortly after the start of topical methchlorethamine. Dermal-epidermal separation has been reported to occur with topical methchlorethamine on histological examination. It is plausible that the compromised dermal-epidermal junction may manifest as a clinical bulla after a secondary insult. To our knowledge, clinical bulla formation due to topical methchlorethamine has not been reported.

Aged↗
PubMed2005

Tissue immunoexpression and messenger ribonucleic acid localization of inhibin/activin subunit in human epididymis.

OBJECTIVE: To determine the expression of inhibin betaA and betaB subunits and follistatin and the ability of human epididymal epithelium to synthesize these molecules. DESIGN: The main aim of this study was to investigate the expression of inhibin alpha, betaA, and betaB-subunits and follistatin in human epididymis with immunohistochemistry, in situ hybridization, and Western blotting in adult life. SETTING: Academic university hospital. PATIENT(S): Epididymes were obtained from 10 men undergoing routine vasectomy or surgery for benign disease at the Royal Hallamshire Hospital, Sheffield, United Kingdom. MAIN OUTCOME MEASURE(S): Immunoexpression of activin betaA and betaB subunits and follistatin proteins and mRNA in human caput and cauda epididymis. RESULT(S): Positive immunoexpression for activin betaA and betaB subunits and follistatin were detected in different parts of the epididymis epithelium. Western blotting under a reducing condition detected a 28-kd band (possibly corresponding to the activin dimer). In situ hybridization indicated positive mRNA localization signal in both caput and cauda epididymal epithelium. CONCLUSION(S): Activins betaA and betaB subunits, but not inhibin alpha subunit, were detected in epididymal epithelium. These finding suggest that activins might have a role in the processes of sperm maturation and sperm fertilizing capability during transit and storage.

Adult↗
PubMed2004

Transient visual loss may anticipate occipital infarction from hemodialysis.

BACKGROUND: The aim of this study was to report on a patient who had occipital infarction from intradialytic hypotension and review the literature on hemodialysis and visual loss. METHODS: Neuro-ophthalmologic examination and magnetic resonance imaging (MRI) of the brain were conducted. RESULTS: A 61-year-old woman had acute onset of a right homonymous superior quadrantic visual field defect during dialysis after several episodes of transient visual loss associated with symptomatic intradialytic hypotension. MRI showed acute infarction in the left occipital lobe. CONCLUSION: Visual loss is an uncommon complication of hemodialysis. The mechanism usually is related to hypotension and is usually from anterior ischemic optic neuropathy. Although cortical blindness secondary to stroke has been reported as a complication after hemodialysis, we were unable to find another report of visual loss secondary to stroke attributed to intradialytic hypotension with preceding episodes of transient visual loss. Transient visual loss may be a risk factor for stroke during hemodialysis.

Blindness↗
PubMed2004

Recent advances in endometriosis with emphasis on pathogenesis, molecular pathology, and neoplastic transformation.

This article reviews recent advances in our understanding of endometriosis with special reference to its pathogenesis, recent molecular studies, and relationship to neoplasia. Pathogenetic factors include familial predisposition, immunological factors, cell adhesion factors, angiogenic factors, and hormonal factors. Recent molecular findings in endometriosis include the monoclonality of endometriotic cysts and loss of heterozygosity in the majority of cases associated with adenocarcinoma. Women with a long-standing history of endometriosis have an increased risk of ovarian cancer, most commonly endometrioid and clear cell adenocarcinomas. In these cases, there is a high frequency of atypia in the endometriosis, and the endometriosis and the associated ovarian carcinoma may show identical PTEN mutations.

Carcinoma, Endometrioid↗
PubMed2003

A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous recombination at DNA replication forks.

Homologous recombination repair (HRR) is required for both the repair of DNA double strand breaks (DSBs) and the maintenance of the integrity of DNA replication forks. To determine the effect of a mutant allele of the RAD51 paralog XRCC2 (342delT) found in an HRR-defective tumour cell line, 342delT was introduced into HRR proficient cells containing a recombination reporter substrate. In one set of transfectants, expression of 342delT conferred sensitivity to thymidine and mitomycin C and suppressed HRR induced at the recombination reporter by thymidine but not by DSBs. In a second set of transfectants, the expression of 342delT was accompanied by a decreased level of the full-length XRCC2. These cells were defective in the induction of HRR by either thymidine or DSBs. Thus 342delT suppresses recombination induced by thymidine in a dominant negative manner while recombination induced by DSBs appears to depend upon the level of XRCC2 as well as the expression of the mutant XRCC2 allele. These results suggest that HRR pathways responding to stalled replication forks or DSBs are genetically distinguishable. They further suggest a critical role for XRCC2 in HRR at replication forks, possibly in the loading of RAD51 onto gapped DNA.

Base Pair Mismatch↗
PubMed2003

Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy.

Macrophages accumulate in ischemic areas of such pathological tissues as solid tumors, atherosclerotic plaques and arthritic joints. Studies have suggested that hypoxia alters the phenotype of macrophages in a way that promotes these lesions. However, the genes up-regulated by macrophages in such hypoxic tissues are poorly characterized. Here, we have used cDNA array hybridization to investigate the effects of hypoxia on the mRNAs of 1185 genes in primary human monocyte-derived macrophages. As shown previously in other cell types, mRNA levels for vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT-1) were up-regulated by hypoxia. However, the mRNAs of other genes were also up-regulated including matrix metalloproteinase-7 (MMP-7), neuromedin B receptor, and the DNA-binding protein inhibitor, Id2. The promoters of GLUT-1 and MMP-7 confer hypoxic inducibility on a reporter gene in RAW 264.7 macrophages, indicating that the hypoxic up-regulation of these mRNAs may occur, at least in part, at the transcriptional level. GLUT-1 and MMP-7 mRNA were also shown to be up-regulated in hypoxic macrophages in vitro by real-time RT-PCR, and these proteins were elevated in hypoxic macrophages in vitro and in hypoxic areas of human breast tumors. The hypoxia up-regulated genes identified could be important for the survival and functioning of macrophages in hypoxic diseased tissues, and their promoters could prove useful in macrophage-delivered gene therapy.

Animals↗
PubMed2002

Effect on endometrium of long term treatment with continuous combined oestrogen-progestogen replacement therapy: follow up study.

OBJECTIVE: To determine effects of five years of treatment with an oral continuous combined regimen of 2 mg 17beta-oestradiol and 1 mg norethisterone acetate on endometrial histology in postmenopausal women. DESIGN: Follow up study in postmenopausal women. SETTING: 31 menopause clinics in the United Kingdom. PARTICIPANTS: 534 postmenopausal women, all with an intact uterus, who had completed nine months of treatment with oral continuous combined 2 mg 17beta-oestradiol and 1 mg norethisterone acetate agreed to take part in a long term follow up study. Women were assigned to different groups on the basis of the treatment status immediately before entering the original study: 360 women had taken sequential oestrogen-progestogen hormone replacement therapy, 164 had taken no hormone replacement therapy, and 10 had taken unopposed oestrogen therapy. METHODS: Endometrial aspiration specimens were taken before the women started the continuous combined regimen, after 9 and 24-36 months, and at the end of the five year treatment period or on withdrawal from the study. MAIN OUTCOME MEASURE: Results of endometrial histology. RESULTS: The duration of treatment with continuous combined hormone replacement therapy was 4.4 (range 1.1-5.9) years. Data on endometrial specimens were available for 526 women after nine months of treatment, 465 women after 24-36 months of treatment, and 398 women who completed the five years treatment (345 women) or were withdrawn between the two latter visits for biopsies (53 women). No cases of endometrial hyperplasia or malignancy were detected at biopsy; 69% of women had an endometrium classified as atrophic or unassessable on completion of the study or withdrawal from it. Before the continuous combined therapy was started, complex hyperplasia was detected in 21 women who had taken sequential hormone replacement therapy before the study and in one who had taken unopposed oestrogen. All of these women had normal results on histological examination of endometrial tissue after nine months of treatment with continuous combined hormone replacement therapy, and hyperplasia did not recur after up to five years of treatment. CONCLUSIONS: Long term treatment (for up to five years) with continuous combined hormone replacement therapy containing oestradiol 2 mg and norethisterone 1 mg daily was associated with neither endometrial hyperplasia nor malignancy. In women who had complex hyperplasia during previous sequential or unopposed regimens, the endometrium returned to normal during treatment with continuous combined hormone replacement therapy. These findings provide reassurance about the long term safety of this continuous combined regimen in terms of the endometrium.

Administration, Oral↗
PubMed2002

Expression of HIF-1alpha by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy.

Large numbers of monocytes extravasate from the blood into human tumours, where they differentiate into macrophages. In both breast and prostate carcinomas, these cells accumulate in areas of low oxygen tension (hypoxia), where they respond to hypoxia with the up-regulation of one or more hypoxia-inducible factors (HIFs). These then accumulate in the nucleus and bind to short DNA sequences called hypoxia-response elements (HREs) near or in such oxygen-sensitive genes as that encoding the pro-angiogenic factor vascular endothelial growth factor (VEGF). This stimulates gene expression and could explain why, in part, macrophages express abundant VEGF only in avascular, hypoxic areas of breast carcinomas. It also suggests that macrophages could be used to deliver HRE-regulated therapeutic genes specifically to hypoxic tumour areas. A recent study suggested that hypoxic macrophages accumulate HIF-2 rather than HIF-1, prompting the search for HRE constructs that optimally bind HIF-2 for use in macrophage-based gene therapy protocols. However, the present study shows that human macrophages accumulate higher levels of HIF-1 than HIF-2 when exposed to tumour-specific levels of hypoxia in vitro; that macrophages in human tumours express abundant HIF-1; and that expression from HRE-driven reporter constructs in the human macrophage-like cell line MonoMac 6 correlates more closely with HIF-1 than with HIF-2 up-regulation under hypoxia. Taken together, these findings suggest that HIF-1 may be the major hypoxia-inducible transcription factor in macrophages and that HIF-1-regulated constructs are likely to be effective in macrophage delivery of hypoxia-regulated gene therapy to human tumours.

Antigens, CD↗
PubMed2002

Symposium part IV: investigative approaches to endocervical pathology.

There is continuing interest in the study of adenocarcinoma of the cervix and its precursors because of its increase in incidence, both absolute and relative, to squamous neoplasia and the complexity of benign glandular lesions with which endocervical neoplasia may be confused. Investigative techniques may be applied as aids to diagnosis, as prognostic markers, and to further our understanding of etiopathogenesis. This article focuses on recent developments in the four areas of epithelial glycoproteins, molecular markers, cell proliferation markers, and human papillomaviruses as applied to endocervical pathology. Although immunohistochemistry remains dominant, a wide range of other techniques is discussed.

Adenocarcinoma↗