Search PubMed⌕ Search

Biomedical subjects

M Scott

Publications and source records attributed to M Scott.

At least 181 records · Page 10Linked to original sources
PubMed1995

Measurement of urinary desmosine as an indicator of acute pulmonary disease.

A modified radioimmunoassay (RIA) for desmosine in the urine was investigated as a tool for the rapid estimation of lung elastin catabolism. Cystic fibrosis (CF) and oxygen toxicity were chosen as conditions that might show altered elastin destruction. Using an antibody bound to magnetic particles the RIA was adapted to handle large numbers of samples requiring only 50 microliters or urine. The experiments show that it was not necessary to hydrolyze or extract the urine prior to assay and that collecting spot urines and normalizing the data to urine creatinine gives the same interpretation of the data as total desmosine in a 24-hour collection. Urine desmosine levels were elevated in 10 of 16 patients with CF; however, daily fluctuations were considerable in some subjects, varying as much as 5-fold and underlining the importance of assaying several consecutive days of urine in acute disorders for an accurate estimate of desmosine excretion. The RIA for desmosine is a rapid and sensitive assay that requires no sample preparation and could be applied to clinical situations that require large numbers of samples.

Acute Disease↗
PubMed1995

Long-term effects of cognitive-behavioural therapy and lithium therapy on depression in the elderly.

BACKGROUND: We examine the effects of cognitive-behavioural therapy (CBT) as an adjuvant to acute physical treatment and lithium maintenance therapy in reducing depression severity over a follow-up year in elderly depressed patients. METHOD: The study consists of three phases. During the acute treatment and continuation phase, 17 of 31 patients received CBT as an adjuvant to treatment as usual. During the maintenance phase of 1 year, subjects were entered into a double-blind, placebo-controlled study of low-dose lithium therapy. RESULTS: Receiving adjuvant CBT significantly reduced patients' scores on the Hamilton Rating Scale for Depression during the follow-up year (repeated measures analyses of variance; P = 0.007). No significant differences were found between lithium and placebo maintenance therapy. CONCLUSIONS: CBT can be adapted as an adjuvant therapy in the treatment of severely depressed elderly patients and reduces depression severity during follow-up. The prophylactic failure of long-term lithium therapy may be explained through poor compliance.

Aged↗
PubMed1995

Extent of variability inherent in measurements of CD34-positive cells in different human haemopoietic tissues.

Estimation of CD34 expression is widely used to detect and quantify progenitor cells in haemopoietic tissues used as stem cell sources for transplantation. Mouse monoclonal antibodies to CD34 recognise different epitopes of the mucin-like sialoglycoprotein. These epitopes can be grouped into three classes by their differing sensitivities to the enzymes: neuraminidase, chymopapain and glycoprotease. We have compared the expression, by flow cytometry, of the three CD34 epitopes on normal adult and fetal haemopoietic tissue and in chronic myeloid leukaemia, and have used four antibodies from each class to assess variability of staining within and between epitope classes. The results reveal variable expression of CD34 both within and between tissue types and antibody classes. As a result of the different levels of detection by different antibodies, the apparent number of CD34-positive cells vary by approximately 6-fold. Enrichment for CD34 cells using magnetic bead technology shows a significant difference in the percentage of CD34 cells detected for two of the epitope types.

Adult↗
PubMed1994

Structure of the catalytic core of the family F xylanase from Pseudomonas fluorescens and identification of the xylopentaose-binding sites.

BACKGROUND: Sequence alignment suggests that xylanases evolved from two ancestral proteins and therefore can be grouped into two families, designated F and G. Family F enzymes show no sequence similarity with any known structure and their architecture is unknown. Studies of an inactive enzyme-substrate complex will help to elucidate the structural basis of binding and catalysis in the family F xylanases. RESULTS: We have therefore determined the crystal structure of the catalytic domain of a family F enzyme, Pseudomonas fluorescens subsp. cellulosa xylanase A, at 2.5 A resolution and a crystallographic R-factor of 0.20. The structure was solved using an engineered catalytic core in which the nucleophilic glutamate was replaced by a cysteine. As expected, this yielded both high-quality mercurial derivatives and an inactive enzyme which enabled the preparation of the inactive enzyme-substrate complex in the crystal. We show that family F xylanases are eight-fold alpha/beta-barrels (TIM barrels) with two active-site glutamates, one of which is the nucleophile and the other the acid-base. Xylopentaose binds to five subsites A-E with the cleaved bond between subsites D and E. Ca2+ binding, remote from the active-site glutamates, stabilizes the structure and may be involved in the binding of extended substrates. CONCLUSIONS: The architecture of P. fluorescens subsp. cellulosa has been determined crystallographically to be a commonly occurring enzyme fold, the eight-fold alpha/beta-barrel. Xylopentaose binds across the carboxy-terminal end of the alpha/beta-barrel in an active-site cleft which contains the two catalytic glutamates.

Amino Acid Sequence↗
PubMed1994

Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.

Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrPSc (where PrPSc is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrPSc. The patterns of MHu2MPrPSc and MoPrPSc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease > 500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.

Animals↗
PubMed1994

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

Two lines of transgenic (Tg) mice expressing high (H) levels of the mutant P101L prion protein (PrP) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated Tg(MoPrP-P101L)H. Brain homogenates from Tg(MoPrP-P101L)H mice were inoculated intracerebrally into CD-1 Swiss mice, Syrian hamsters, and Tg196 mice, Tg mice expressing the MoPrP-P101L transgene at low levels. None of the CD-1 mice developed central nervous system dysfunction, whereas approximately 10% of hamsters and approximately 40% of the Tg196 mice manifested neurologic signs between 117 and 639 days after inoculation. Serial transmission of neurodegeneration in Tg196 mice and Syrian hamsters was initiated with brain extracts, producing incubation times of approximately 400 and approximately 75 days, respectively. Although the Tg(MoPrP-P101L)H mice appear to accumulate only low levels of infections prions in their brains, the serial transmission of disease to inoculated recipients argues that prion formation occurs de novo in the brains of these uninoculated animals. These Tg mouse studies, taken together with similar findings in humans dying of inherited prion diseases, provide additional evidence that prions lack a foreign nucleic acid.

Animals↗
PubMed1994

Treatment of stiff-man syndrome with intravenous immune globulin.

OBJECTIVE: To evaluate the efficacy of intravenous immune globulin (IVIG) in the treatment of stiff-man syndrome (SMS). METHODS: An open, unblinded study of 3 patients with active disease and/or disease refractory to treatment with diazepam and/or corticosteroids. RESULTS: All 3 bedridden patients improved substantially shortly after infusion with IVIG and regained function. CONCLUSION: IVIG may be useful for the treatment of SMS.

Adult↗
PubMed1994

Lunular hypertrophy and aortic valve disease.

Cuspid malcoaptation secondary to abnormal hypertrophy in combination with stiffening involving the line of apposition (lunular hypertrophy) has not been recognized as a cause of aortic valve dysfunction. This entity was found in 50 adults (mean age, 62 years). Thirty-three had pure aortic valve insufficiency (> or = 3+, n = 13; < 3+, n = 20), 13 had mixed aortic valve insufficiency and stenosis (> or = 3+, n = 2; < 3+, n = 11), and 4 had pure aortic valve stenosis. Forty-one had a history of rheumatic heart disease and advanced mitral valve disease, and 7 had coronary artery disease. All underwent shaving of the hypertrophic protuberances, which in 26 patients constituted the entire aortic valve repair. In the remaining 24 patients, aortic valve repair included one or more additional procedures; there were 15 commissurotomies, 12 debridements of calcium deposits from the base of the cusps, and 5 cusp resuspensions. Concomitant mitral valve repair was performed in 26 patients, mitral valve replacement in 15, tricuspid valve repair in 11, coronary artery bypass grafting in 7, and repair of an ascending aortic aneurysm in 2. In 2 patients, the attempt to repair the aortic valve was unsuccessful, necessitating valve replacement. There were 5 operative deaths (10%), but none were related to aortic valve repair. Forty-three patients entered follow-up (mean, 56 +/- 57 months). Three patients (7%) suffered late recurrent aortic valve insufficiency (at 6, 48, and 72 months). The remaining 40 patients (93%) had trivial or no recurrent aortic valve dysfunction. The 6-year actuarial freedom from aortic valve-related problems was 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The role of ultrasound imaging in the diagnosis of breast implant rupture: a prospective study.

Breast ultrasound to assess possible implant rupture was performed on 24 consecutive patients (43 breasts) by the same radiologist immediately before revisional breast implant surgery. Comparison of the clinical, ultrasound and operative findings showed ultrasound to be three times as sensitive as clinical judgement in predicting implant rupture. The sensitivity of ultrasound in predicting impaired implant integrity was 70% (versus 23% for clinical examination) with a specificity of 96%. The ultrasound features indicating leakage are outlined later. The positive predictive value of an abnormal scan was 90% and that of a normal scan 87%. It is concluded that breast ultrasound is a simple, quick, non-invasive method which contributes significantly to the assessment of patients with suspected breast implant rupture.

Adult↗
PubMed1994

Optimal primer selection for clonality assessment by polymerase chain reaction analysis: II. Follicular lymphomas.

Prior studies have shown variable success in amplification of monoclonal B-cell populations from follicular lymphomas (FLs) of germinal center cell origin using the polymerase chain reaction (PCR). We examined 60 FLs by the PCR to determine optimal primer selection for detection of clonal immunoglobulin heavy chain gene (IgH) rearrangements in this common group of B-cell lymphomas. Each primer set included a 3' IgH joining region consensus primer; the 5' primer was different in each reaction. The first-line panel included the following: Set 1, bcl-2 major breakpoint region (mbr) primer; Set 2, bcl-2 minor cluster region (mcr) primer; Set 3, IgH variable region framework III consensus primer; and Set 4, seven separate IgH variable region framework I family-specific primers. A reserve panel also was used. The efficiency of monoclonal B-cell population amplification differed among primer sets. The bcl-2-targeted primer pairs (Sets 1 and 2) were most efficient and amplified 42 (70%) of 60 cases. Of these, the mbr and mcr primer sets detected monoclonality in 38 and four cases, respectively. Set 3 amplified monoclonal B-cell in 38 and four cases, respectively. Set 3 amplified monoclonal B-cell populations in 31 (52%) cases and Set 4 detected similar populations in only 27 (45%) samples. When results from primer Sets 1, 2, and 3 were combined, 49 of 60 (82%) FLs showed evidence of B-cell monoclonality by the PCR. Three of the 11 negative cases were documented as monoclonal with primer Set 4, and three additional samples were amplified only with our reserve panel.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Establishment of a human retinal cell line by transfection of SV40 T antigen gene with potential to undergo neuronal differentiation.

Recently, a number of laboratories have been interested in developing cell lines of ocular tissues to understand the pathogenesis of ocular diseases. Toward this end, we report here the generation of cell lines of human retina by transfection of simian virus SV40 T antigen gene. Established retinal cells grow as a monolayer and exhibit limited serum dependence. Phase-contrast and electron microscopic studies revealed distinct morphological cell types. Immunofluorescence studies showed that the established retinal cells were positive for neuron-specific enolase, neurofilament protein, glycine receptor, synaptophysin, and secretogranin. Cells were negative for glial fibrillary acidic protein, glutamine synthetase, galactocerebroside, and carbonic anhydrase II. In addition to neuronal features, a small percentage of flat cells were, however, positive for cellular retinaldehyde binding protein, and cells with the phenotype of rod and cone photoreceptor coexpressed opsin and interphotoreceptor retinoid-binding protein. An important feature of this cell line is that addition of phorbol ester and cAMP induced dramatic changes, with 100% of the cells extending long, thin neuritic processes. Thus, the established retinal cells would be useful for studies dealing with differentiation and plasticity of the cells of the nervous system.

Antigens, Polyomavirus Transforming↗