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Biomedical subjects

M O Smith

Publications and source records attributed to M O Smith.

At least 19 recordsLinked to original sources
PubMed2006

ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).

Mutation in the CHMP2B gene has been implicated in frontotemporal dementia. The authors screened CHMP2B in patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) in two patients with non-SOD1 ALS. Neuropathology of the Q206H case showed lower motor neuron predominant disease with ubiquitylated inclusions in motor neurons. Antibodies to p62 (sequestosome 1) showed novel oligodendroglial inclusions in the motor cortex.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Supplementation of zinc from organic or inorganic source improves performance and antioxidant status of heat-distressed quail.

Two sources of zinc [ZnSO4.H2O or ZnPicolinate (ZnPic)] supplementation were evaluated for their effects on performance, carcass weight, levels of malondialdehyde, and vitamins C, E, A in Japanese quail (Coturnix coturnix Japonica) exposed to high ambient temperature of 34 degrees C. The birds (n = 360; 10-d-old) were randomly assigned to 12 treatment groups consisting of 3 replicates of 10 birds each in a 2 x 2 x 3 factorial arrangement of treatments (temperatures, zinc sources, zinc levels). Birds were kept in wire cages in a temperature-controlled room at either 22 degrees C (thermoneutral) or 34 degrees C (heat stress) for 8 h/d (0900 to 1700 h) until the end of study, and fed a basal (control) diet or the basal diet supplemented with either 30 or 60 mg of Zn as ZnSO4 H2O or ZnPic/kg of diet. Heat exposure decreased (P = 0.001) live weight gain, feed intake, feed efficiency, and carcass weight when the basal diet was fed. A linear increase in feed intake (P = 0.01) and BW (P = 0.01), and improvement in feed efficiency (P = 0.01) and carcass weight (P < or = 0.05) were found in zinc-supplemented quail reared under heat-stress conditions. Serum vitamin C (P = 0.04), E (P = 0.05), and cholesterol (P = 0.01) concentrations increased linearly, whereas malondialdehyde concentrations decreased linearly (P = 0.02) as dietary zinc sulfate and ZnPic supplementation increased. An interaction between dietary zinc sources, temperature, and levels of supplementation (P < or = 0.05) for these parameters was detected. Serum vitamins C, E, and A concentrations were not different in supplemented birds reared at thermoneutral temperature. Supplementation with zinc improved carcass weight and antioxidant status of birds, and the effects of ZnPic were relatively greater than those of ZnSO4.H2O in heat-stressed quail. Results of the present study suggest that supplementation with ZnPic could be considered to be more protective than ZnSO4.H2O by reducing the negative effects of oxidative stress induced by heat stress in quail.

Animal Nutritional Physiological Phenomena↗
PubMed2004

Use of volatile fatty acids from an acid-phase digester for denitrification.

This study investigates the ability of naturally-produced volatile fatty acids (VFAs) to act as a carbon source for the removal of nitrate-Nitrogen concentrations in the range of 20 to 200 mg/L. The VFAs were generated from an anaerobic digester treating a 1:1 mixture of starch-rich industrial and municipal wastewater. The experiments were carried out at an ambient temperature of 22+/-2 degrees C using 600 mL batch reactors containing VFA-rich effluent from the digester and prepared primary sludge. Nitrates added in the form of a 1 M potassium nitrate solution were observed to completely disappear in conjunction with significant recovery of pH and alkalinity (i.e. biological denitrification). In all cases, denitrification followed zero-order kinetics with an average rate constant of 2.67 mg/[Lh] and a mean specific denitrification rate of 0.0111 g NOx-N/g volatile suspended solids (VSS) per day. The denitrifier population had a preference for acetic acid which occurred in the largest quantity and was exhausted the most rapidly. The next two most abundant VFAs were butyric acid and propionic acid, which were consumed only after acetate concentrations began to decline. The third "choice" of the denitrifiers was valeric acid, thus it appears that denitrifying bacteria have a sequential preference for VFAs. In addition, they prefer VFAs over other more complex soluble organic carbon forms.

Anaerobiosis↗
PubMed2004

Ascorbic acid and melatonin reduce heat-induced performance inhibition and oxidative stress in Japanese quails.

1. The effects of ascorbic acid (L-ascorbic acid) and melatonin supplementation on performance, carcase characteristics, malondialdehyde (MDA) as lipid peroxidation indicator, ascorbic acid, retinol, tocopherol and mineral status in the Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature were evaluated. 2. Two hundred and forty Japanese quails (10 d old) were randomly assigned to 8 treatment groups consisting of 10 replicates of three birds each. The birds were kept in a temperature-controlled room at 22 degrees C (Thermoneutral, TN groups) or 34 degrees C (for 8 h/d; 09:00 to 17:00 h; Heat stress, HS groups). Birds in both TN and HS were fed either a basal (control) diet or the basal diet supplemented with 250 mg of L-ascorbic acid/kg of diet (Ascorbic acid group), 40 mg of melatonin/kg of diet (Melatonin group) or both (Ascorbic acid + Melatonin group). 3. Supplementing heat-stressed quails with ascorbic acid and melatonin improved performance compared with the control group. Effects generally were greatest in quails supplemented with both ascorbic acid and melatonin. 4. Although supplementation did not consistently restore the concentrations of serum ascorbic acid, retinol and tocopherol to those of TN groups, these concentrations increased significantly with supplementation. Furthermore, serum and liver MDA and serum cholesterol and glucose concentrations were lower in the supplemented groups than in the heat-stressed controls. 5. Within each environment, excretion of Ca, P, Mg, Zn, Fe and Cr were lowest in the combination group and, in all cases, highest in the HS group. Interactions between diet and temperature were detected for live weight gain, cold carcase weight, MDA, ascorbic acid, tocopherol concentrations and excretion of zinc. 6. The results of the study indicate that ascorbic acid and melatonin supplementation attenuate the decline in performance and antioxidant and mineral status caused by heat stress and such supplementation may offer protection against heat-stress-related depression in performance of Japanese quails.

Animals↗
PubMed2003

In vivo antioxidant properties of vitamin E and chromium in cold-stressed Japanese quails.

An experiment was conducted to determine if vitamin E (alpha-tocopherol-acetate) and chromium (chromium picolinate, Cr Pic) supplementation attenuate the negative effects of cold stress on egg production, egg quality, serum metabolites, and antioxidant status in Japanese quails (Corurnix coturnix japonica). One hundred and fifty laying Japanese quails (50-day-old) were divided into five groups, 30 birds per group. The laying quails kept at 6 degrees C for 12 h/d (08.00 p.m. to 08.00 a.m.) were fed either a basal diet (low temperature-basal diet, CS group) or the basal diet supplemented with either 400 microg of Cr/kg of diet (Cr group), 250 mg of alpha-tocopherol-acetate per kg of diet (Vit. E group) or 400 microg of Cr plus 250 mg of alpha-tocopherol-acetate per kg of diet (Vit. E + Cr group) while quails kept at 18 degrees C were fed a basal diet (thermo-neutral-basal diet, TN group). Performance and egg quality were significantly reduced in CS group compared with TN group. Supplemental chromium and vitamin E significantly increased live weight change, egg production, and improved feed efficiency in cold-stressed laying hens compared with the group fed the basal diet at 6 degrees C. Egg production and egg weight were also greater (P < 0.05) in each supplemental group compared with the CS group. However, a combination of vitamin E and chromium, rather than each separately, provided the greatest performance. Supplemental vitamin E and chromium also increased serum vitamin C and E but, decreased malondialdehyde (MDA) concentrations (P < 0.05); the combination of vitamin E and chromium resulted in the highest levels of serum vitamin C and E within the cold-stressed quails. Results of the present study indicate that combined antioxidant supplements increased performance, egg quality and serum antioxidant levels while lowering MDA in cold-stressed quails.

Animal Feed↗
PubMed2003

Effects of different levels of zinc on the performance and immunocompetence of broilers under heat stress.

Male broilers were used to evaluate the effect of zinc on performance and immune competence during heat stress (HS). Broilers raised in either a thermoneutral (TN, 23.9 degrees C constant) or HS (23.9 to 35 degrees C cycling) environment were fed a low zinc diet (LZ; 34 mg/kg), an adequate zinc diet (AZ; 68 mg/kg), or a supplemental zinc diet (HZ; 181 mg/kg). Humoral immunity was assessed by intravenous injection of 7% SRBC followed by evaluation of serum for antibody titers in primary and secondary responses. Cell-mediated immunity was assessed using a Sephadex stimulation method to recruit abdominal exudate cells (AEC) to evaluate macrophage phagocytic ability. The HS birds consumed 12.5% less feed, gained 24.6% less weight, and had lower feed efficiency when compared to TN birds. Dietary zinc levels did not impact growth performance or plasma zinc concentration. Numbers of AEC, macrophages in AEC, phagocytic macrophages, and internalized opsonized and unopsonized SRBC were increased by HZ. Total, IgM, and IgG antibody titers for primary and secondary responses were significantly increased in birds receiving HZ under TN conditions. Tibia zinc concentration increased with increasing zinc levels but did not change with temperature. Lymphoid organ weights, primary and secondary antibody responses, incidences of macrophages in AEC, phagocytic ability of macrophages, and plasma zinc concentration were all significantly reduced by HS. These results indicate that the immune response of broilers can be influenced by the level of zinc in the diet and by environmental conditions.

Abdomen↗
PubMed2002

Monitoring tumour cells in the peripheral blood of small cell lung cancer patients.

BACKGROUND: Flow cytometry was used to enumerate tumour cells in longitudinal studies of peripheral blood from small cell lung cancer (SCLC) patients, together with magnetic bead selection to isolate and identify these cells. As part of a trial, 11 patients received either standard (four weekly) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) or accelerated (two weekly) ICE with filgrastim (granulocyte colony-stimulating factor [G-CSF]) and autologous stem cell support. METHODS: Fresh venous blood was taken throughout treatment and follow-up. Aliquots were stained with a "tumour-specific" antibody against epithelial tissue (Ber EP4), verified as a good marker of SCLC cells by immunohistochemistry. Matched samples labelled with Ber EP4 were separated magnetically by adding a secondary bead-antibody conjugate for confirmation of tumour cell identity. RESULTS: Circulating tumour cells were detected and monitored throughout treatment periods. An initial rise in circulating cells after the first cycle was followed by a fall in both treatment arms to baseline levels set by normal controls. This was achieved by week 12 in the accelerated treatment arm and by week 24 in the standard arm. CONCLUSIONS: Flow cytometry and magnetic bead isolation can be used to identify changes in numbers of circulating tumour cells in patients undergoing chemotherapy for SCLC and thereafter during follow-up periods. Absence of tumour cells may indicate a more favourable patient group who would benefit from a more intense course of treatment.

Antibody Affinity↗
PubMed2001

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease.

A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.

Alanine Transaminase↗
PubMed2000

Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

OBJECTIVE: To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. DESIGN: Prospective study. ANIMALS: 27 healthy sexually intact adult female Beagles. PROCEDURE: Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. RESULTS: Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.

Alkaline Phosphatase↗
PubMed2000

Characteristics of pale, soft, exudative broiler breast meat.

The objective of the study was to characterize pale breast meat, compare it with normal colored breast meat, and determine whether it should be considered pale, soft, and exudative (PSE). Characteristics of 20 normal and 20 pale broiler breasts, obtained at a commercial slaughter plant, were evaluated. Compared with normal meat, the pale breast meat had a significantly (P < 0.05) lower pH (5.7 vs. 5.9), higher color L* value (60.0 vs. 55.1), higher drip loss (1.34 vs. 0.87%), lower marinade uptake (31.2 vs. 44.3%), and lower cooking yields (95.2 vs. 105.8%). Protein solubility in pale samples was slightly (P < 0.05) lower than in normal samples, which suggests increased protein denaturation in the pale breasts. Correlations between pH and L* value (r = -0.76), pH and marinade uptake (r = 0.64), sarcoplasmic protein solubility and L* value (r = -0.71), and sarcoplasmic protein solubility and moisture uptake (r = 0.66) and cooking yield (r = 0.66) were significant (P < 0.05). Correlations between total protein solubility and moisture uptake or cooking yields were not significant. The low ultimate pH of pale breast muscle appears to be the main determinant of its low water-holding capacity (WHC). This lower pH was unrelated to a higher lactate concentration or glycolytic potential of the pale muscle. Further research is needed to determine the causes of the low pH and possible measures to increase the pH (and functionality) of pale broiler breast muscle. Because the pale breast muscle has a low WHC, it can be considered PSE.

Animals↗
PubMed1999

The correlation between cell surface markers and clinical features in choroidal malignant melanomas.

PURPOSE: Uveal melanoma continues to present problems when attempting to predict disease progression. This study attempts to identify markers indicative of the biological characteristics of cells isolated from samples of uveal melanoma, including adhesion (ICAM-1), immune reactivity (MHC Class I and II), cell cycle control (c-erbB-2, c-myc) and apoptosis control (bcl-2, p53) using dual parameter (DNA/MoAb) flow cytometry. METHODS: Sixty-three fresh tissue samples from choroidal melanomas were taken at enucleation. Samples were assayed for DNA content and cell cycle, the above antibodies together with positive (PHM-5) and negative (2 degrees FITC Ab) controls. The clinical parameters sex, age, tumour location, cell type, tumour volume and presence of metastases were compared with the results and analysed with the non-parametric Mann-Whitney U-t-test. RESULTS: ICAM-1 expression proved to be the most clinically relevant, being present on a higher proportion of cells in tumours > 2000 mm3 (median 38, n = 19) compared with the smaller tumours < 2000 mm3 (median 17, n = 26) (p = 0.0015). Metastatic disease was present in 11 patients and did not correlate with any of the surface markers. C-myc, c-erbB-2 and MHC Class II expression were associated with cell type, all showing greater expression in spindle cell tumours than mixed/epithelial types. CONCLUSION: These results show flow cytometry as a quick, easy method to provide a 'phenotypic profile' for these tumours, and identifies cell cycle control and adhesion molecule expression as important areas for further investigation. c-erbB-2 and bcl-2 positivity was typically seen on over 60% cells in each sample, indicating two potential targets for therapeutic intervention.

Adult↗
PubMed1999

Genomic screening for fucosidosis in English Springer Spaniels.

OBJECTIVE: To develop a robust molecular genetic test for alpha-L-fucosidosis in English Springer Spaniels and to screen dogs from the United Kingdom and United States for the mutant allele. ANIMALS: 35 English-bred English Springer Spaniels, 60 American-bred English Springer Spaniels, and 1 affected dog and its parents from a family of English Springer Spaniels in Colorado. PROCEDURE: Polymerase chain reaction analysis was used to amplify the mutated region in the gene encoding alpha-L-fucosidase. High guanine-cytosine (GC) content of the region required use of an amplification buffer with high pH. Mutant and normal alleles were separated by polyacrylamide gel electrophoresis. Molecular genetic test results were compared with enzyme data. RESULTS: A 262-bp PCR product was amplified from normal dogs and compared with a 248-bp product from affected dogs. Carriers had 1 copy of each allele, distinguishable by the 14-bp size difference. Two carriers among the English-bred dogs were identified by use of enzyme and genomic DNA analyses. The molecular defect in dogs from Colorado was proven to be the same as that in British and Australian dogs. None of the other 60 American-bred dogs carried the mutant allele. CONCLUSIONS AND CLINICAL RELEVANCE: A PCR method that can be used to identify dogs affected with or carriers of the autosomal recessive disease fucosidosis was established. Amplification was achieved within a GC-rich region, using a method that may be useful in overcoming amplification problems in GC-rich areas within other genes. Using this test, fucosidosis can be controlled and ultimately eradicated from the English Springer Spaniel population.

Animals↗
PubMed1998

Simultaneous cell cycle and phenotypic analysis of primary uveal melanoma by flow cytometry.

BACKGROUND AND PURPOSE: DNA ploidy and cell cycle measurements of uveal melanoma tissue are regarded as having limited prognostic significance. In contrast, dual-parameter (DNA monoclonal antibody) flow cytometry offers a convenient and rapid way to screen tumour samples for a variety of phenotypic markers, whilst simultaneously measuring DNA ploidy and cell cycle, and therefore has the increased potential to identify clinically relevant indicators of disease progression. The aim of the present study was to identify a simple yet robust method for isolating, preserving and staining cells that could be analysed by flow cytometry. METHODS: Using a simple preparation procedure, a panel of membrane-associated antibodies (ICAM-1, W632, HLA-DR) and nuclear or cytoplasmic oncoprotein antibodies (c-erbB-2, c-myc, bcl-2, p53), together with positive (PHM-5) and negative (FITC F(ab')2) controls, were assayed. It was considered important to test the protocol with markers expressed on the cell surface, and in the cytoplasm and nucleus, so as not to be restrictive and thereby exclude an antigen of potential clinical interest. In addition, such panels would also enable the generation of a 'phenotypic profile' for each specimen that may reveal clinically significant trends. RESULTS: Our results indicate that tissue dissociation followed by brief fixation in 1% paraformaldehyde and permeabilisation in 70% methanol produces a stable single cell suspension, which can subsequently be stained with a wide range of antibodies for the accurate identification of cells in a potentially heterogeneous tumour population. CONCLUSION: This technology can rapidly identify sub-populations of cells expressing differing levels of proteins, which may prove to be indicative of disease progression for this aggressive disease.

Antibodies, Monoclonal↗
PubMed1998

A randomised trial of the durability of non-allergenic latex-free surgical gloves versus latex gloves.

A prospective randomised trial was performed to compare the robustness of a new non-latex surgical glove with a standard latex glove when worn by four general surgeons in a district general hospital. Gloves were retrieved after surgery and examined using the European Standard Test for punctures. The overall puncture rate was 10.1%, and there was no significant difference in the rates between the two types of glove, although punctures in the non-latex glove tended to be larger and more readily noted by the wearer. The increase in latex allergy among health care staff dictates the need for gloves made from other materials, which may also be useful for operations on latex-allergic patients.

Attitude of Health Personnel↗
PubMed1997

Effects of iatrogenic blood contamination on results of cerebrospinal fluid analysis in clinically normal dogs and dogs with neurologic disease.

OBJECTIVE: To examine the effects that iatrogenic blood contamination would have on total protein concentration and nucleated cell count in CSF from clinically normal dogs and dogs with neurologic disease. DESIGN: Case-control study. STUDY POPULATION: 53 dogs confirmed to have neurologic disease and 21 clinically normal dogs. PROCEDURE: CSF samples were obtained from the cerebellomedullary cistern or the lumbar portion of the subarachnoid space. Red blood and nucleated cell counts were determined, and protein concentration was measured. RESULTS: RBC count was not significantly correlated with nucleated cell count or protein concentration in clinically normal dogs or dogs with neurologic disease. CLINICAL IMPLICATIONS: High CSF nucleated cell counts and protein concentrations are indicative of neurologic disease, even if samples contain moderate amounts of blood contamination.

Analysis of Variance↗
PubMed1997

Clinical evaluation of cimetidine, sucralfate, and misoprostol for prevention of gastrointestinal tract bleeding in dogs undergoing spinal surgery.

OBJECTIVE: To determine the incidence of gastrointestinal (GI) tract bleeding in dogs undergoing spinal surgery with adjunct corticosteroid treatment, and to determine the protective efficacy of cimetidine, sucralfate, and misoprostol against such bleeding in these dogs. ANIMALS: 40 dogs that underwent spinal surgery. PROCEDURES: Myelography and surgery were performed on the first or second day of hospitalization. Methylprednisolone sodium succinate was given at a dosage of 30 mg/kg of body weight prior to myelography, followed by a second full or half dose 2 to 4 hours later at clinician discretion. Spinal surgery was performed in conventional manner, postoperative administration of analgesics was done, and dogs were fed a diet lacking red meat. Dogs were assigned at random to 1 of the 3 treatment groups or to the control group. Dogs of the treatment groups received cimetidine, sucralfate, or misoprostol. Physical examination and determination of PCV and serum total protein values were performed daily. A fecal sample was examined daily for gross and occult blood. RESULTS: 36 of 40 dogs had GI tract bleeding during a hospitalization period of 3 to 6 days. There was no significant difference in development of bleeding between the control group and any of the treatment groups. CONCLUSIONS: Gastrointestinal tract bleeding occurred in 90% of dogs undergoing spinal surgery combined with administration of methylprednisilone sodium succinate, a higher rate than that found in previous studies. This bleeding was not life-threatening. Prophylactic benefit from any of the GI protectants tested was not found.

Adrenal Cortex Hormones↗