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Biomedical subjects

M Moody

Publications and source records attributed to M Moody.

At least 19 recordsLinked to original sources

A randomised, double-blind, placebo-controlled trial of a recombinant version of human alpha-fetoprotein (MM-093) in patients with active rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. OBJECTIVE: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. METHODS: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. RESULTS: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient's global assessment (28.9% vs -36.3%, p = 0.02) compared with placebo. CONCLUSION: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.

Arthritis, Rheumatoid↗

Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease.

The human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high-throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I-infected individuals. Our study group consisted of 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral peaks corresponding to peptide ions were generated from MS-TOF data. We applied Classification and Regression Tree analysis to build a decision algorithm, which achieved 77% correct classification rate across the three groups. A second cohort of 10 ATL, 10 HAM and 10 control samples was used to validate this result. Linear discriminate analysis was performed to verify and visualize class separation. Affinity and sizing chromatography coupled with tandem mass spectrometry was used to identify three peaks specifically overexpressed in ATL: an 11.7 kDa fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 and 11.9 kDa) of haproglobin-2. To the best of our knowledge, this is the first application of protein profiling to distinguish between two disease states resulting from a single infectious agent.

Adolescent↗

Membrane-Permeant 3-OH-Phosphorylated Phosphoinositide Derivatives.

A crucial role in the regulation of epithelial chloride secretion is played by the phosphoinositide PtdIns(3,4,5)P3 . Membrane-permeant derivatives of this and other naturally occurring phosphoinositides have been synthesized. These derivatives, which can be bioactivated, were used in investigations on nasal epithelia of patients suffering from cystic fibrosis.

cyclitols↗

Elevated proapoptotic Bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome.

OBJECTIVE: Salivary gland epithelial cells in patients with Sjögren's syndrome (SS) and in NOD and NODscid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-xL, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. METHODS: Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohistochemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. RESULTS: Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. CONCLUSION: These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS.

Animals↗

Salivary anti-spectrin autoantibodies in Sjögren's syndrome.

OBJECTIVE: The purpose of this study was done to compare the anti-spectrin autoantibody levels in the parotid saliva of Sjögren's syndrome patients and in the parotid saliva of healthy control subjects. METHODS: The salivary anti-spectrin autoantibody levels of 20 Sjögren's patients and of 20 healthy controls were compared by means of the slot blot immunoassay and the alkaline phosphatase method. RESULTS: Various anti-spectrin autoantibody levels were detected in the saliva of both patients and controls. The color intensity of the blots was scored on a scale of 1 to 3. The scores were deemed to indicate the anti-spectrin autoantibody levels in saliva (1 = low, 2 = moderate, and 3 = high). The Mann-Whitney U test did not reveal a significant difference in the anti-spectrin autoantibody levels of patients and the anti-spectrin autoantibody levels of controls (P > or = .31). These results do not support a pathologic role for anti-spectrin autoantibody in Sjögren's syndrome. CONCLUSIONS: The overall result of this study substantiates that anti-spectrin autoantibodies occur naturally in saliva. Their role in immune surveillance or pathology is not clear at present.

Autoantibodies↗

Use of formalin-fixed, propidium iodide-stained human leukocytes as a standard for enumerating CD4+ T lymphocytes in a single-platform assay.

A new, inexpensive method is described that enables lymphocytes to be enumerated very precisely. Normal leukocytes were simultaneously stained and fixed with a propidium iodide-paraformaldehyde solution. The preparation obtained (CellBeads) was used as an internal standard for cell enumeration by flow cytometry and was stable at 4 degrees C for at least 60 days. Unlike synthetic beads, the CellBeads behaved similarly to normal cells during red blood cell lysis and cell washing procedures. When known numbers of CellBeads were added to whole-blood samples and the numbers of CellBeads and lymphocytes were determined, highly reproducible and accurate enumerations were obtained-far more so than when synthetic beads were used. This inexpensive method is suitable for routine use.

CD3 Complex↗

An investigation of the factors affecting community pharmacists' selection of over the counter preparations.

A postal survey of pharmacists in a random sample of community pharmacies in Great Britain was carried out to ascertain the factors which influenced their decisions when recommending a product for Over The Counter (OTC) sale. Six categories of condition which regularly present in community pharmacies were selected and the pharmacists were asked to state which first line product they would recommend for each condition, in an uncomplicated situation with no other relevant problems. Of the 1138 questionnaires sent, 635 were suitable for analysis giving a response rate of 56.7%. The recommendations were found to be appropriate in 99.7% of cases. Factors which had the greatest influence on product selection were active ingredients, evidence of product efficacy, ease of use by patient and patient characteristics such as age and concurrent medication. Economic factors such as profit, pressures of excess stock and product promotion by sales representatives were shown to have a significantly greater influence on proprietor pharmacists than the other categories of pharmacist. The results of this study suggest that in the majority of cases pharmacists' decisions on OTC drug therapy are based on clinical and patient factors and whilst commercial factors may be involved they do not compromise the quality of the recommendations.

Adult↗

Novel method for processing respiratory specimens for detection of mycobacteria by using C18-carboxypropylbetaine: blinded study.

A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced. This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no. 78195-27-4), also known as C18-carboxypropylbetaine (CB-18). In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory specimens were tested. Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics--Baltimore. A total of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters. Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18. The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing. There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens. The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity. This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.

Bacteriological Techniques↗

Intermittent sequential compression therapy in lower limb disorders.

The development of more compact equipment and multi-chambered compression garments has extended the use of intermittent compression therapy in the treatment of venous insufficiency and venous ulcers, lymphoedema and lipodermatosclerosis. Further research into the therapeutic effects of this therapy is required.

Aged↗

Managing sacral pressure ulcers with hydrocolloid dressings: results of a controlled, clinical study.

One-hundred and three patients with Stage II and III sacral pressure ulcers were enrolled in a prospective, controlled, multi-center clinical study to evaluate and compare dressing performance, safety and efficacy. Fifty-two patients were randomized to treatment with a triangle-shaped hydrocolloid border dressing and 51 patients were randomized to a different, oval shape, hydrocolloid dressing. The majority of patients (70 percent) utilized a pressure reducing mattress or bed. Most ulcers were Stage II, had existed for < 1 month and exhibited no change utilizing previous treatments. Patients and wounds were similarly distributed among treatment groups. Patients in the oval dressing group were more likely to exhibit a product related adverse reaction resulting in discontinuation of treatment as compared to patients treated with the triangle border dressing (p = 0.057, Fisher's Exact Test). Wear time was longest for wounds dressed with the triangle dressing applied point down. Incontinence reduced the interval between dressing changes in both groups. Healing was more likely to occur in wounds dressed with the triangle border dressing. These ulcers showed a greater reduction in ulcer width as compared to wounds dressed with the oval dressing (p < 0.03, Fisher's Exact Test).

Aged↗

Creation of an inositol 1,4,5-trisphosphate-sensitive Ca2+ store in secretory granules of insulin-producing cells.

A rapid rise in the cytosolic free Ca2+ concentration due to influx of extracellular Ca2+ or mobilization from intracellular stores is the primary trigger for exocytosis from secretory cells. Our understanding as to the precise role of Ca2+ mobilization has been complicated by the presence of several types of Ca2+ stores in most cells. We now demonstrate that overexpression of the type 3 inositol 1,4,5-trisphosphate (IP3) receptor in insulin-secreting beta TC-3 cells results in the creation of a unique IP3-sensitive Ca2+ pool, restricted to the insulin secretory granules of these cells.

Amino Acid Sequence↗

Evaluation of a semipermeable polyurethane absorptive dressing.

While semipermeable film dressings are well established for treatment of moist wounds, they lose moisture to the atmosphere at a fixed rate. This article reports an evaluation of a semipermeable dressing recently made available in the UK which claims to vary the rate of moisture vapour loss.

Adolescent↗

Let us extend our knowledge base. Assessment and management of fungating malignant wounds.

Little research has been undertaken on the management of fungating malignant wounds, and current practice relies more upon an exploratory approach than research-based evidence. This article presents a detailed problem-solving framework for the assessment and management of these wounds, and can be used in conjunction with the wallchart outlining the plan enclosed free with this issue.

Bandages↗