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Biomedical subjects

J Matthews

Publications and source records attributed to J Matthews.

At least 73 records · Page 4Linked to original sources

The accuracy of home glucose meters for the glucose range anticipated in pregnancy.

Home glucose meters are used almost universally for the management of pregnant women with diabetes. However, the degree of accuracy of meters in general and particularly for the lower glucose range, is questionable. Six of the most commonly used meters in Australia were evaluated for analytical accuracy for glucose levels < 8.0 mmol/L--a level below which many important clinical management decisions are made. Two meters, Elite and Precision QID, cannot be recommended. The other 4 meters, Glucometer 3, Reflolux S, Alpha and Advantage produced results with a higher degree of analytical accuracy. Of the meters tested, the Accutrend Alpha had the highest proportion of results within 5% and 10% of a laboratory reference method, the lowest bias with the Altman Bland method of comparison, and is recommended for use in pregnancy. No meter approached the analytical accuracy goal recommended by the American Diabetes Association. Manufacturers should be encouraged to develop or adapt systems for use in pregnancy.

Adult↗

Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain.

Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2) due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta-chain and the common gamma-chain receptor in addition to one other IL-15 binding receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase-polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL-15 fusion protein in immunoperoxidase and flow cytometric experiments. In addition, IL-15, but not IL-2, accelerates and enhances the development of transepithelial resistance across T84 monolayers in a dose-dependent fashion. We conclude that normal and T84 colonic epithelial cells express IL-15R alpha and are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in the absence of IL-2R beta-chain in T84 cells.

Cell Division↗

Are dependency and self-criticism risk factors for major depressive disorder?

OBJECTIVE: To determine whether dependent and self-critical personality traits are associated with specific types of life events and whether these traits change with pharmacotherapy. METHOD: Overall, 142 depressed outpatients completing 8 weeks of fluoxetine treatment were administered the Life Experiences Survey (LES) at baseline and the Dysfunctional Attitude Scale (DAS) and Hamilton Depression Rating Scale (HDRS) at baseline and endpoint. RESULTS: The DAS dependency subscale, but not the self-criticism subscale, showed significant correlations with life events regardless of congruency. Baseline HDRS scores were positively correlated with both DAS subscales and total score. The DAS subscales, the total DAS score, and the HDRS all improved significantly with treatment. CONCLUSIONS: These results confirm a growing body of research that has found an association between sociotropic or dependent personality traits and life events.

Adult↗

Prognostic value of cytogenetic abnormalities in previously untreated patients with non-Hodgkin's lymphoma.

In this study cytogenetic findings have been correlated with prognosis in 78 previously untreated patients with non-Hodgkin's lymphoma (NHL) presenting between 1983 and 1988. The median follow-up was 7 years (range 2-9 years). There was no significant difference in the duration of survival of 33 patients with only abnormal karyotypes, 35 patients with a mixture of normal and abnormal karyotypes (AN) and 10 patients with only normal karyotypes (NN). This was true for the entire group (p = 0.6) as well as for the subsets of diffuse lymphomas (DL) and follicular lymphomas (FL) (p = 0.6 and 0.4, respectively). Monosomy 14 was the only abnormality in the entire group of patients to be associated with a statistically significant difference in survival duration (p = 0.046). Among the FL patients, trisomy 7 (p = 0.046) and trisomy 12 (p = 0.010) were associated with shorter survival. Presence of t(14;18) did not influence survival in the entire group (p = 0.16), nor in any of the histological subgroups. Among the FL patients with t(14;18), presence of additional cytogenetic abnormalities was not associated with a worse outcome. The lack of consistency of results between various studies is likely to be due to several factors and the prognostic significance of karyotypic abnormalities can only be clarified by large prospective studies employing uniform treatment policies.

Adolescent↗

Fucosidosis in a family of American-bred English Springer Spaniels.

Fucosidosis was detected in a family of English Springer Spaniels in the United States. To our knowledge, these are the first reported cases of this disease in American-bred dogs. Affected and carrier status of dogs were determined by measuring the activity of the enzyme alpha-L-fucosidase in plasma and in leukocytes. Fucosidosis results in neurologic signs, particularly changes in behavior, in adolescent and adult dogs. Late onset of signs may result in misdiagnosis as a primary behavior problem or acquired neurologic disease. Fucosidosis is inherited in an autosomal recessive manner, and carrier dogs are clinically normal. Thus, the abnormal gene can become widespread in a population before homozygous-affected dogs are produced.

Animals↗

Homozygous and compound heterozygous mutations at the Werner syndrome locus.

The Werner syndrome (WS) is a rare autosomal recessive progeroid disorder. The Werner syndrome gene (WRN) has recently been identified as a member of the helicase family. Four distinct mutations were previously reported in three Japanese and one Syrian WS pedigrees. The latter mutation was originally described as a 4 bp deletion spanning a spliced junction. It is now shown that this mutation results in a 4 bp deletion at the beginning of an exon. Nine new WRN mutations in 10 additional WS patients, both Japanese and Caucasian, are described. These include three compound heterozygotes (one Japanese and two Caucasian). The new mutations are located all across the coding region.

Asian People↗

Hemodynamic characterization of a novel neuropeptide Y receptor antagonist.

Defining the roles of the vasoconstrictor peptide neuropeptide Y (NPY) in the cardiovascular system is difficult due to lack of availability of specific NPY receptor antagonists. We report the in vivo NPY receptor blocking actions of a novel nonapeptide dimer, 1229U91 {(IleGluProDprTyrArgLeuArgTyrNH(2)(2)}, and describe its hemodynamic effects. In anesthetized normotensive rats, 1229U91 produced significant and dose-dependent reductions in NPY-reduced hemodynamic responses. 1229U91 (3-30 nmol/kg intravenously, i.v.) attenuated the pressor response (34 +/- 6-84 +/- 1%) and the increases in renal vascular resistance (RVR, 56 +/- 9-94 +/- 2%) produced by NPY (1 nmol/kg i.v.). Intravenous norepinephrine (NE)-induced hemodynamic responses were not altered by 1229U91. 1229U91 also produced dose-dependent inhibition of NPYinduced vasoconstrictor responses in anesthetized dogs and spontaneously hypertensive rats (SHR). These data demonstrate that 1229U91 is a selective NPY receptor antagonist. 1229U91 had no effect on resting hemodynamic variables in these preparations. In conscious SHR, 1229U91 did not produce significant changes in blood pressure (BP) or heart rate (HR) over a wide dose-range (15-1,500 nmol/kg i.v.). Lack of effect of the NPY receptor antagonist in SHR suggests that NPY does not contribute to the maintenance of BP in this hypertension model.

Anesthesia↗

Immunocytochemical labelling of aerobic and hypoxic mammalian cells using a platinated derivative of EF5.

The monoclonal antibody ELK3-51 was previously developed to detect adducts of the 2-nitroimidazole EF5. Direct immunofluorescence was used to detect adducts of EF5 or of a platinated derivative cis-[PtCl2(NH3)EF5] in SCCVII cells treated under aerobic or hypoxic conditions. Fluorescence measurements of these cells using both image and flow cytometric methods were compared, giving similar profiles. Platination significantly decreased immunofluorescence levels (approximately 4-fold less than EF5) after 3 h in hypoxia, but also increased levels after exposure in air (approximately 1.5 x) such that the hypoxic ratio decreased from approximately 50 to approximately 13. Platinated EF5 also showed significantly greater cytotoxicity than its parent in both aerobic and hypoxic cells. These results are consistent with targeting of EF5 to DNA, which was confirmed qualitatively by confocal microscopy.

Animals↗

Comparison of the specificity of bacterially expressed cytoplasmic protein-tyrosine phosphatases SHP and SH-PTP2 towards synthetic phosphopeptide substrates.

SHP and SH-PTP2 are related cytoplasmic protein-tyrosine phosphatases having two tandem amino-terminal src homology 2 domains linked to a single catalytic domain. There is growing evidence that these two molecules may exhibit opposing effects within specific signaling pathways. However, the relative contributions of the src homology 2 domains or the catalytic domains to these opposing effects are not well known. To evaluate the potential contribution of the catalytic domains, we compared the substrate specificity of the two phosphatases. As seen previously, the catalytic activities of bacterially expressed SHP and SH-PTP2 were regulated by the presence of the linked src homology 2 domains. In addition, we characterized a cryptic thrombin cleavage site within the carboxy-terminus of SHP that led to a striking increase in the activity of the catalytic domain. Employing a panel of phosphopeptide substrates whose sequences were modeled after intracellular phosphorylation sites, both SHP and SH-PTP2 demonstrated a similar specificity pattern. Similar to SH-PTP2, SHP failed to elicit detectable phosphate release from several phosphopeptide substrates, while displaying catalytic efficiencies that ranged over approximately 40-1.6 x 10(3) M-1 s-1 towards other substrates. In contrast, the PTP-1B phosphatase dephosphorylated all of the phosphopeptide substrates tested with approximately equal ease. The overall similarity demonstrated by the catalytic domains of SHP and SH-PTP2 suggested that differences in the in vivo behavior of these two molecules might not stem from differences in the substrate specificity of the catalytic domains, suggesting instead that the specificity of the src homology 2 domains is more important in this regard.

Amino Acid Sequence↗

Novel modified carboxy terminal fragments of neuropeptide Y with high affinity for Y2-type receptors and potent functional antagonism at a Y1-type receptor.

Peptide analogs of neuropeptide Y (NPY) with a Tyr-32 and Leu-34 replacement resulted in the decapeptide TyrIleAsnLeuIleTyrArgLeuArgTyr-NH2 (9; Table 1) and a 3700-fold improvement in affinity at Y2 (rat brain; IC50 = 8.2 +/- 3 nM) receptors when compared to the native NPY(27-36) C-terminal fragment. In addition, compound 9 was an agonist at Y1 (human erythroleukemia (HEL) cell; ED50 = 8.8 +/- 0.5 nM) receptors with potency comparable to that of NPY(1-36) (ED50 = 5 nM). Molecular dynamics and 1H-NMR were used to propose a solution structure of decapeptide 9 and for subsequent analog design. The replacement of Leu with Pro at position 4 of decapeptide 9 afforded an antagonist of NPY in HEL cells (18, TyrIleAsnProIleTyrArgLeuArgTyr-NH2; IC50 = 100 +/- 5 nM). Deletion of the N-terminal tyrosine of 18 resulted in a 10-fold improvement in antagonistic activity with a parallel 4-fold decrease in Y2 affinity. This potent antagonist may provide further insight into the physiological role(s) for NPY in the mammalian and peripheral nervous system.

Amino Acid Sequence↗

Synovial hemangioma: imaging features in eight histologically proven cases, review of the literature, and differential diagnosis.

OBJECTIVE: This study was undertaken to describe the imaging characteristics of synovial hemangioma, with the goal of improving the disappointing rate (22%) of clinical diagnosis of this condition. A review of the literature and the differential diagnosis of intra-articular lesions, including synovial osteochondromatosis and pigmented villonodular synovitis, are also presented. PATIENTS: The subjects of the study were 8 patients (4 males, 4 females; age range: 5-47 years; mean age: 19 years) with histologically confirmed synovial hemangioma involving the knee (n = 7) or wrist (n = 1). We retrospectively examined the imaging studies performed in these patients, including plain radiography (n = 8), magnetic resonance imaging (MRI; n = 4), angiography (n = 3), arthrography (n = 2), and contrast-enhanced computed tomography (CT; n = 2). RESULTS: Plain radiographs showed a soft tissue density suggesting either joint effusion or a mass in all patients. Phleboliths and bone erosions on plain films in four patients with extra-articular soft tissue involvement pointed to the correct diagnosis. Angiography, showing fine-caliber, smooth-walled vessels, contrast pooling in dilated vascular spaces, and early visualization of venous structures, was diagnostic in two patients. Neither arthrography nor CT yielded specific enough findings. MRI was consistently effective in allowing the correct diagnosis to be made preoperatively, showing an intra-articular or juxta-articular mass of intermediate signal intensity on T1-weighted images and of high signal intensity of T2- or T2*-weighted images with low-signal channels or septa within it. A fluid-fluid level was found in two patients with a cavernous-type lesion. CONCLUSION: Despite the limited nature of this study, it shows clearly that MRI is the procedure of choice whenever an intra-articular vascular lesion such as synovial hemangioma is suspected. Nonetheless, phleboliths and evidence of extra-articular extension of plain radiographs point to angiography as an effective procedure of first resort because it can be combined with embolotherapy.

Adolescent↗

Scedosporium prolificans, a multi-resistant fungus, from a U.K. AIDS patient.

We report the first isolation of Scedosporium prolificans (inflatum) in the U.K. The patient, with advanced AIDS and neutropenia, had respiratory tract colonisation over many months without invasive disease despite neutropenia, while on itraconazole therapy. The organism was resistant in vitro to all licensed systemic antifungal agents tested.

AIDS-Related Opportunistic Infections↗

Protective role of lactulose in intestinal carcinogenesis.

Primary bile acids are converted to carcinogenic secondary bile acids by colonic bacteria when the colonic pH is high. Therefore acidification of the luminal contents may reduce the cancer risk. The ability of lactulose to reduce colonic pH, secondary bile acid production, mucosa crypt cell production rate and tumour formation was measured in a rat model of intestinal carcinogenesis. Eighty Wistar rats were divided into four groups receiving normal diet alone or with lactulose, azoxymethane or both azoxymethane and lactulose. The addition of lactulose was associated with a significant fall in small intestinal and colonic pH. Lactulose was associated with a sharp rise in the secondary to primary bile acid ratio. The crypt cell production rate fell significantly with lactulose. The addition of lactulose was associated with a significantly reduced tumour yield in small intestine but not in colon. Lactulose therefore can reduce this is of no value in humans at risk of developing colorectal carcinoma.

Acid-Base Imbalance↗

Mantle cell lymphoma: natural history defined in a serially biopsied population over a 20-year period.

BACKGROUND: The histological, immunological and molecular characteristics of mantle cell lymphoma have only recently been delineated. Amongst these characteristics possible factors of prognostic significance include histological growth pattern and blastoid change. PATIENTS AND METHODS: 66 previously untreated cases of mantle cell lymphoma were identified in a retrospective analysis. In 50 cases serial biopsies had been taken during the disease and in 20 cases autopsies had been performed. Besides established factors of prognostic significance, histological growth pattern and blastoid change were examined. RESULTS: 32 patients achieved an initial complete remission or good partial remission with most cases relapsing or progressing within 2 years. The median survival was 36 months. Factors predicting a poor outcome were high presenting stage, age > 70, low sodium, low albumin and splenomegaly. Blastoid transformation was also a poor prognostic feature, occurring in 32% of cases during life and in 70% of autopsies. Histological growth pattern had no influence on outcome. CONCLUSION: This study emphasises the difficulties in treating mantle cell lymphoma and the high frequency and prognostic importance of histological transformation.

Aged↗

Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center.

PURPOSE: To examine outcome of treatment for patients with recurrent follicular lymphoma. PATIENTS AND METHODS: Two hundred twelve newly diagnosed follicular lymphoma patients were studied. One hundred seventy-nine were initially treated successfully. Recurrent or progressive lymphoma developed in 116. Treatment was given according to disease stage and current protocols, mostly with single alkylating agents. A policy of repeated lymph node and bone marrow biopsy was pursued. RESULTS: The overall median survival duration was 9 years, with a median follow-up duration of 12 years. Following recurrence, the median survival duration was 4 1/2 years. Only eight of 116 patients with recurrent disease died of causes unrelated to lymphoma. The overall response rate to first re-treatment was 78% and showed slight decline with successive recurrences, reaching 48% after the fourth treatment. The median duration of second remission was 13 months, (v 31 months for first remission), with the only significant predictive factor being quality of remission. Multivariate analysis showed only age at recurrence and number of prior treatments to correlate with survival after first recurrence. Survival after second remission was only correlated with age and quality of response: Kaplan-Meier estimates gave 53% of patients reaching second complete remission alive 10 years later, compared with 28% in partial remission. CONCLUSION: Age and previous and continuing responsiveness of follicular lymphoma to therapy are the principal determinants of survival following recurrence. Improvement in survival with new treatments will be demonstrated most readily in older patients, while more intensive approaches should be tested in younger patients in whom remission is achieved with difficulty.

Age Factors↗

Design of a fully integrated three-dimensional computed tomography simulator and preliminary clinical evaluation.

PURPOSE: We describe the conceptual structure and process of a fully integrated three-dimensional (3-D) computed tomography (CT) simulator and present a preliminary clinical and financial evaluation of our current system. METHODS AND MATERIALS: This is a preliminary report on 117 patients treated with external beam radiation therapy alone on whom a 3-D simulation and treatment plan and delivery were carried out from July 1, 1992, through June 30, 1993. The elements of a fully integrated 3-D CT simulator were identified: (a) volumetric definition of tumor volume and patient anatomy obtained with a CT scanner, (b) virtual simulation for beam setup and digitally reconstructed radiographs, (c) 3-D treatment planning for volumetric dose computation and plan evaluation, (d) patient-marking device to outline portal on patient's skin, and (e) verification (physical) simulation to verify portal placement on the patient. Actual time-motion (time and effort) recording was made by each professional involved in the various steps of the 3-D simulation and treatment planning on computer-compatible forms. Data were correlated with the anatomic site of the primary tumor being planned. Cost accounting of revenues and operation of the CT simulator and the 3-D planning was carried out, and projected costs per examination, depending on case load, were generated. RESULTS: Average time for CT volumetric simulation was 74 min without or 84 min with contrast material. Average times were 36 min for contouring of tumor/target volume and 44 min for normal anatomy, 78 min for treatment planning, 53 min for plan evaluation/optimization, and 58 min for verification simulation. There were significant variations in time and effort according to the specific anatomic location of the tumor. Portal marking of patient on the CT simulator was not consistently satisfactory, and this procedure was usually carried out on the physical simulator. Based on actual budgetary information, the cost of a volumetric CT simulation (separate from the 3-D treatment planning) showed that 1500 examinations per year (six per day in 250 working days) must be performed to make the operation of the device cost effective. The same financial projections for the entire 3-D planning process and verification yielded five plans per day. Some features were identified that will improve the use of the 3-D simulator, and solutions are offered to incorporate them in existing devices. CONCLUSIONS: Commercially available CT simulators lack some elements that we believe are critical in a fully integrated 3-D CT simulator. Sophisticated 3-D simulation and treatment planning can be carried out in a significant number of patients at a reasonable cost. Time and effort and therefore cost vary according to the anatomic site of the tumor being planned and the number of procedures performed. Further efforts are necessary, with collaboration of radiation oncologists, physicists, and manufacturers, to develop more versatile and efficient 3-D CT simulators, and additional clinical experience is required to make this technology cost effective in standard radiation therapy of patients with cancer.

Adult↗

Prognostic value of immunophenotyping in acute myeloid leukemia. Australian Leukaemia Study Group.

The diagnostic and prognostic value of immunophenotyping with 18 murine monoclonal antibodies (MoAbs) to a variety of leukocyte differentiation antigens was assessed in 168 adults aged 15 to 60 years with acute myeloid leukemia (AML). Patients were entered on the multicentre Australian Leukaemia Study Group M4 protocol, and were randomized to receive either standard or high-dose Ara-C together with daunorubicin and etoposide as induction chemotherapy, followed by standard consolidation and maintenance therapy. Diagnostic bone marrow aspirate (152 cases) or peripheral blood samples (16) were analyzed by indirect immunofluorescence and flow cytometry. MoAbs used were directed at myeloid (CD11b, CD13, CD14, CD15, CD33, CD41), lymphoid (CD2, CD3, CD7, CD9, CD10, CD19), or stem cell (HLA-DR, CD34, c-kit receptor) antigens, as well as the leukocyte integrins CD18 and CD49e, and the transferrin receptor CD71. Of the myeloid markers, CD13 and CD33 were the most useful diagnostically (71% and 79% of cases positive, respectively), with CD11b, CD14, and CD15 less commonly positive. A minority of cases expressed lymphoid antigens, either T cell (CD2 16%, CD3 7%, CD7 28%) or B cell (CD10 2%, CD19 7%). CD34 was detected on 42% and c-kit receptor on 48%. When patients were analyzed for response to treatment, CD2, CD9, and CD14 were significantly associated with complete remission rate: cases expressing these antigens had a poorer response than negative cases. In univariate analysis, CD11b+ cases had shorter periods of remission (relative risk of relapse, 2.33; P = .003) and shorter survival (relative death rate, 1.91; P = .006). In multivariate analysis, adjusting for other prognostic factors, CD9 and CD11b were significantly predictive of shorter survival. No other marker had a significant predictive effect. We conclude that myeloid MoAbs are useful in confirming the diagnosis of AML, but their prognostic value may be limited to CD11b. Lymphoid antigen expression is a consistent phenomenon in a minority of cases of AML, but appears to have little clinical significance.

Acute Disease↗