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Biomedical subjects

M Glover

Publications and source records attributed to M Glover.

At least 19 recordsLinked to original sources
PubMed2004

A new autologous keratinocyte dressing treatment for non-healing diabetic neuropathic foot ulcers.

AIMS: To evaluate the use of a new cell-tailored carrier surface (TranCell) for delivery of autologous keratinocytes to promote wound healing in patients with chronic neuropathic foot ulcers. METHODS: TranCell is a sterile medical grade polymer coated with a plasma-polymerized functional surface containing 20% carboxylic acid which enables keratinocytes to attach and proliferate. Six diabetic patients with neuropathic ulcers resistant to conventional therapy were treated with weekly applications of autologous keratinocytes delivered on TranCell. A split-thickness skin biopsy was taken from each patient followed by isolation, expansion and freezing down of keratinocytes. Keratinocytes were thawed and seeded on TranCell 48 h prior to application. This procedure was repeated weekly in addition to conventional therapy until wound healing was achieved. RESULTS: Complete healing was achieved in six out of nine ulcers in six patients, a reduction in ulcer size was achieved in one ulcer and no response was seen in one ulcer. Treatment was discontinued in one patient due to development of Methicillin-Resistant Staphylococcus aureus (MRSA) after only three applications of TranCell. Wound healing took 6-17 applications over 6-20 weeks. There were no recurrences in the healed ulcers after a follow-up of 6 months. CONCLUSIONS: TranCell delivery of autologous cells is a promising treatment for chronic diabetic foot ulcers with no side-effects and no recurrence in the healed ulcers.

Adult↗
PubMed2001

Structure of a conjugating enzyme-ubiquitin thiolester intermediate reveals a novel role for the ubiquitin tail.

BACKGROUND: Ubiquitin-conjugating enzymes (E2s) are central enzymes involved in ubiquitin-mediated protein degradation. During this process, ubiquitin (Ub) and the E2 protein form an unstable E2-Ub thiolester intermediate prior to the transfer of ubiquitin to an E3-ligase protein and the labeling of a substrate for degradation. A series of complex interactions occur among the target substrate, ubiquitin, E2, and E3 in order to efficiently facilitate the transfer of the ubiquitin molecule. However, due to the inherent instability of the E2-Ub thiolester, the structural details of this complex intermediate are not known. RESULTS: A three-dimensional model of the E2-Ub thiolester intermediate has been determined for the catalytic domain of the E2 protein Ubc1 (Ubc1(Delta450)) and ubiquitin from S. cerevisiae. The interface of the E2-Ub intermediate was determined by kinetically monitoring thiolester formation by 1H-(15)N HSQC spectra by using combinations of 15N-labeled and unlabeled Ubc1(Delta450) and Ub proteins. By using the surface interface as a guide and the X-ray structures of Ub and the 1.9 A structure of Ubc1(Delta450) determined here, docking simulations followed by energy minimization were used to produce the first model of a E2-Ub thiolester intermediate. CONCLUSIONS: Complementary surfaces were found on the E2 and Ub proteins whereby the C terminus of Ub wraps around the E2 protein terminating in the thiolester between C88 (Ubc1(Delta450)) and G76 (Ub). The model supports in vivo and in vitro experiments of E2 derivatives carrying surface residue substitutions. Furthermore, the model provides insights into the arrangement of Ub, E2, and E3 within a ternary targeting complex.

Computer Simulation↗
PubMed2001

Production, characterization, and epitope mapping of monoclonal antibodies against human polydeoxyribonucleotide kinase.

Polydeoxyribonucleotide kinase (PNK) is a mammalian DNA repair enzyme that has the capacity to phosphorylate 5' DNA termini and dephosphorylate 3' DNA termini. A series of murine monoclonal antibodies (MAbs) was raised against the full-length recombinant human PNK. Seven of these antibodies were selected and characterized by enzyme immunoassay, Western blot analysis, and their capacity to immunoprecipitate PNK. The epitope location was defined by cyanogen bromide digestion and by using a truncated PNK for Western blot analysis. All of the MAbs recognize a single 60-kDa protein in human cell extracts. PNKs from calf, monkey, and Chinese hamster cell and tissue extracts were also detected by some or all of the MAbs. These antibodies can be successfully used for the cellular, biochemical, and functional analysis of PNK in different mammalian cell lines.

Amino Acid Sequence↗
PubMed2001

Medical versus surgical androgen suppression therapy for prostate cancer: a 10-year longitudinal cost study.

PURPOSE: We provide a relative cost comparison of medical versus surgical androgen suppressive therapy for prostate cancer. MATERIALS AND METHODS: Comparison is based on a cohort of 96 patients who began androgen suppressive therapy for prostate cancer between 1988 and 1990. Patients were followed until death or the end point of study in June 2000 at which time 15% were alive. Current Medicare orchiectomy reimbursements were compared to 1999 wholesale drug costs. RESULTS: For an individual patient the cost of luteinizing hormone releasing hormone (LH-RH) agonist treatment surpassed the cost of surgery at less than 4.2 to 5.3 months, and for combined androgen blockade (LH-RH agonists and nonsteroidal antiandrogens) at less than 2.7 to 3.4 months. For 5 (5.2%) patients on combined androgen blockade and 6 (6.3%) on LH-RH agonists alone, medical therapy would have had a cost advantage over bilateral orchiectomy. For the androgen suppression cohort the cost of LH-RH agonist treatment was 10.7 to 13.5 times and combined androgen blockade was 17.3 to 20.9 times the cost of bilateral orchiectomy. Urology resource use comparisons are provided. These findings significantly underestimate the cost advantage of surgery. A seventh of the patients were alive at study end point, and prostate specific antigen induced stage shifting and changes in practice patterns resulted in earlier and more frequent androgen suppressive treatment. CONCLUSIONS: Except for patients with short anticipated survivals current medical androgen suppressive treatment options are more costly than bilateral orchiectomy. There is a need for a cost comparable medical option to orchiectomy.

Androgen Antagonists↗
PubMed2000

Fecal shedding of Campylobacter and Arcobacter spp. in dairy cattle.

Campylobacter jejuni, Campylobacter coli, and Arcobacter spp. were detected in feces of healthy dairy cows by highly specific multiplex-PCR assays. For C. jejuni, at this one-time sampling, cows from 80.6% of farm operations (n = 31) and 37.7% of individual dairy cattle fecal samples (n = 2,085) were positive. Farm management factors were correlated with prevalence in herds in which >25% of cows were positive for C. jejuni. Statistical significance was set at a P of 0.20. Using these criteria, application of manure with broadcast spreaders (P = 0.17), feeding of whole cottonseed or hulls (P = 0.17) or alfalfa (P = 0.15), and accessibility of feed to birds (P = 0.17) were identified as possible risk factors for C. jejuni infection. C. coli was detected in at least one animal in 19.4% of operations and 1.8% of individual cows (n = 2,085). At the herd level, use of broadcaster spreaders was not a risk factor for C. coli infection. For Arcobacter, cows from 71% of dairy operations (n = 31) and 14.3% of individual dairy cattle fecal samples (n = 1,682) were positive. At the herd level, for Arcobacter spp., feeding of alfalfa (P = 0.11) and use of individual waterers (P = 0.19) were protective. This is the first description of Arcobacter spp. in clinically healthy dairy cattle and the first attempt to correlate their presence with C. jejuni.

Animal Feed↗
PubMed1999

Building community for the long-term: an intergenerational commitment.

Intergenerational visitation programs have demonstrated advantages for the young and old, but few programs last more than a year or two. Weaving long-term intergenerational programs into the fabric of both school curricula and community cultural life was the goal of a project launched in 1988 in Phoenix, Arizona. Classrooms of children visit weekly or biweekly with nearby nursing home residents, developing friendships while pursuing educational activities. Carefully planned and widespread community support through board participation, donations, and publicity has allowed the program to continue to expand, while the budget has decreased. Materials are available which facilitate program replication.

Aged↗
PubMed1999

SPIKEII: an integrate-and-fire AVLSI chip.

We present the SPIKEII chip, an integrate-and-fire neural network chip with programmable synapses implemented in analogue VLSI. It is the successor to the SPIKEI chip. We describe the circuitry, and show some results using networks of integrate-and-fire neurons.

Action Potentials↗
PubMed1998

An extended alpha-helix and specific amino acid residues opposite the DNA-binding surface of the cAMP response element binding protein basic domain are important for human T cell lymphotropic retrovirus type I Tax binding.

The human T cell lymphotropic retrovirus type I (HTLV-I) trans-activator, Tax, interacts specifically with the basic-domain/leucine-zipper (bZip) protein, cAMP response element binding protein (CREB), bound to the viral Tax-responsive element consisting of three imperfect 21-base pair repeats, each with a cAMP response element core flanked by G/C-rich sequences. Here, the minimal CREB-bZip necessary for Tax binding is shown to be composed of amino acid residues 280-341. The Tax-CREB interaction involves an uninterrupted and extended alpha-helix in CREB that spans most of its basic domain to include amino acid residues localized to the NH2 terminus of the DNA binding region. Mutational analyses indicate that three residues, Arg284, Met291, and Glu299 unique to this region of the CREB/activating transcription factor-1 subfamily of bZip proteins, constitute the contact surface for Tax. Amino acid substitutions in these positions had little impact on CREB-bZip binding to DNA but abrogated its binding to Tax. Each of the contact residues for Tax are spaced approximately two helical turns apart on the side of the bZip helix directly opposite to that of the invariant DNA-binding residues. Molecular modeling reveals the Tax-contact residues to be near the minor groove of the G/C-rich DNA in the 21-base pair repeat. They most likely position Tax for minor groove contact with the G/C-rich sequences.

Amino Acid Sequence↗
PubMed1996

[Purpura fulminans with extensive skin necroses].

Purpura fulminans must be treated as an emergency in internal medicine and dermatology. Its characteristic features are the sudden development of progressively enlarging haemorrhagic skin necrosis, severe disseminated intravascular coagulation with consumption of anticoagulant factors, and signs of shock. Purpura fulminans can be classified into a neonatal form with inherited protein C deficiency and an acquired type for which multiple causes are known. Clinically it is characterized by massive ecchymosis with haemorrhagic blebs and acral necrosis. Histologically the lesions show widespread extravasation of erythrocytes and thrombosis of small vessels. Thrombocytopenia, decrease of coagulation factors, the presence of fibrinogen split products and fragmented erythrocytes in the blood smear help to confirm the diagnosis. The therapy includes fresh-frozen plasma, heparin, antibiotics and surgical debridement of necrotic areas. It is important to recognize the disease promptly because the mortality rate is about 30-40% and only quick intervention helps to save the life of the patient.

Aged↗
PubMed1995

Cutaneous squamoproliferative lesions in renal transplant recipients. Differentiation from lesions in immunocompetent patients.

Of 291 immunosuppressed renal transplant recipients (RTRs) with surviving allografts attending the Royal London Hospital, 171 patients (59%) were found to have warty keratoses. On histological analysis, the lesions in 50 patients (17%) showed partial-thickness dysplasia, and 34 (12%) had one or more invasive squamous cell carcinoma (SCC) and/or one or more in situ SCC or full-thickness dysplasia. We examined the claim that squamoproliferative lesions in RTRs possess distinctive histopathological features that differ from those of similar lesions occurring sporadically in the nonimmunosuppressed population. We compared 40 squamoproliferative lesions from RTRs with 40 matched squamoproliferative lesions from nonimmunosuppressed patients; lesions were coded and their source was unknown to the assessors. Two dermatopathologists independently assessed the cases and gave scores for 11 histological features that have been reported to be characteristic of such lesions in the immunosuppressed population. These included a warty architecture, koilocytes, and multinucleate giant cells. Using these criteria, it was not possible to distinguish lesions of immunosuppressed patients from those of immunocompetent people.

Carcinoma in Situ↗
PubMed1994

Specific types of human papillomavirus found in benign proliferations and carcinomas of the skin in immunosuppressed patients.

A total of 118 biopsies from skin lesions of 46 renal allograft patients was analyzed for human papillomavirus (HPV) DNA by polymerase chain reaction with degenerate primers and also partially by subsequent sequencing of the amplified fragment. Sixty-two % of the benign proliferations (31 of 50) contained DNA of known HPV types as well as HPV sequences related to a number of epidermodysplasia verruciformis-associated HPV types. HPV DNA sequences were found in 14 (56%) of 25 biopsies from squamous cell and basal cell carcinomas. One squamous cell carcinoma contained HPV 41 DNA. A novel 640-base pair fragment sharing homology with HPV 29 (82.7%) was found in 15% (3 of 20) of squamous cell carcinomas, in 9.4% (3 of 32) of dysplastic warts and in 8.5% (4 of 47) common warts. The remaining positive carcinoma biopsies contained HPV-related DNA in such a low copy number that additional analysis is required. The identification of new HPV types in skin cancers of immunosuppressed patients (other than epidermodysplasia verruciformis patients) further expands the spectrum of HPV-linked human malignancies and permits new approaches to study the pathogenesis of skin cancers.

Amino Acid Sequence↗
PubMed1994

An association between psoriasis and hereditary multiple exostoses. A clue for the mapping of a psoriasis susceptibility gene?

Chronic plaque psoriasis affects approximately 1.6% of the U.K. population. Population, family and twin studies all strongly suggest an important genetic component in the pathogenesis of the disease, although genetic linkage studies have, so far, failed to identify susceptibility genes. We describe a family in which psoriasis cosegregates through three generations with a known autosomal dominant disorder, hereditary multiple exostoses (HME). A major locus for HME has recently been mapped to chromosome 8q. Observations in this family may provide a mapping clue for a psoriasis susceptibility gene.

Adult↗
PubMed1993

Fine structure of capillaries in ischaemic and non ischaemic rat striated muscle. Effect of torbafylline.

Capillary ultrastructure was studied in ischaemic and contralateral extensor digitorum longus (EDL) muscle, in the diaphragm and left ventricular papillary muscle of rats with unilateral ligation of the common iliac artery (L), in ischaemic stimulated muscles (SL), and in ischaemic stimulated muscles of animals treated with a new xanthine derivative, torbafylline (SL&T). Muscles were stimulated at 10Hz via implanted electrodes 7 times/day for 2 weeks. Torbafylline or water was given by gavage morning and evening. Nominal evaluation of capillary ultrastructure revealed endothelial swelling in 52.7 +/- 8.7% (mean +/- SEM) capillaries in ischaemic muscles, 35.2 +/- 5.6% in contralateral muscles and about 30% in the diaphragm and papillary muscle. Stimulation of ischaemic muscles increased this proportion to 62.6 +/- 6.2% (not significant vs. L), 57.8 +/- 9.5% (p < 0.05 vs. L), 62.6 +/- 6.3 (p < 0.05 vs. L) and 43.7 +/- 4.2% (p < 0.05 vs. L) in ischaemic and contralateral EDL, diaphragm and papillary muscle, respectively. Administration of torbafylline reduced the proportion of swollen capillaries to 37.8 +/- 6.1.45% (p < 0.02 vs. SL) in ischaemic muscles, and to 26.2 +/- 2.1% (p < 0.001) in papillary muscle, with a smaller effect in the contralateral EDL and the diaphragm. Stereological analysis showed that stimulation led to a marked increase in capillary size vs. contralateral muscles. A similar lumen volume density across all groups (Vv = 0.36-0.39), vs. control Vv = 0.47, reflected structural heterogeneity within the capillary population of EDL. For most components this intra- animal variation obscured drug treatment effects, the exception being Vv(nucleus) which was least in SL&T. Activity in ischaemic muscles can thus result in widespread capillary endothelial damage in muscles, and attenuation of this swelling by torbafylline may explain the beneficial effect of this drug on capillary perfusion and performance.

Animals↗
PubMed1992

Dermatomyositis pemphigoides: a case with coexistent dermatomyositis and bullous pemphigoid.

We describe a patient with coexistent dermatomyositis and bullous pemphigoid; both appeared within a few weeks. Protein blotting showed binding of the patient's serum to the classic 220 kd bullous pemphigoid antigen. Because of the close temporal association of the two disorders, we believe that they are almost certainly etiologically linked. One possibility is that exposure of basement membrane antigens by dermatomyositis led to exposure of bullous pemphigoid antigen and subsequent antibody formation.

Aged↗