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Biomedical subjects

I Miller

Publications and source records attributed to I Miller.

At least 19 recordsLinked to original sources
PubMed2006

Serum levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), -1, -2, -3, in oral cancer.

INTRODUCTION: Insulin-like growth factor (IGF) possesses mitogenic properties promoting cellular proliferation and inhibiting cellular apoptosis. Reported evidence suggests that cancer (non-oral) is associated with high circulating levels of IGF-1 and low levels of IGFBP-3. AIMS: This study measured circulating levels of IFG-1 and IGFBPs -1, -2 and -3 in oral cancer patients. METHODOLOGY: Blood was collected from surgical patients and controls. Samples were assayed for IGF-1 and IGFBPs -1, -2, -3, using commercially available enzyme-linked immunosorbant assays (ELISA; R&D Systems Europe, Oxon, UK). RESULTS: Twenty-seven oral cancer and 31 age- and sex-matched patients were recruited. Mean IGF-1 and IGFBP-3 levels were significantly lower in cancer patients than controls (85.3 ng/ml and 2008 ng/ml versus 191 ng/ml and 2935 ng/ml, P<0.001). In contrast, levels of IGFBPs 1 and 2 were significantly higher in cancer patients than in controls. No significant association was demonstrated with tumour size or nodal metastases. DISCUSSION: This study has shown that in contrast to other cancers, circulating levels of IGF-1 and IGFBP-3 may both be lowered in patients with head and neck cancer.

Biomarkers, Tumor↗
PubMed2006

Detecting oxidative post-translational modifications in proteins.

Oxidative stress induces various post-translational modifications (PTM); some are reversible in vivo via enzymatic catalysis. The present paper reviews specific procedures for the detection of oxidative PTM in proteins, most of them including electrophoresis. Main topics are carbonylated and glutathionylated proteins as well as modification of selected amino acids (Cys, Tyr, Met, Trp, Lys).

Oxidation-Reduction↗
PubMed2006

Epidemiological investigations on Trichinella infections in farmed fur animals of Estonia.

Farming of fur animals represents an important income in Estonia. Even though Trichinella worms does not induce a symptomatic disease in carnivores, the carcasses of skinned animals can increase the biomass of the parasite in the environment, if they are not properly destroyed. The aim of the present survey was to study the prevalence of Trichinella worms in farmed fur animals of Estonia. Of 281 muscle samples from blue foxes (Alopex lagopus), silver foxes (Vulpes vulpes fulva), minks (Mustela vison) and raccoon dogs (Nyctereutes procyonoides), which were collected in eight farms, Trichinella larvae have been detected in 21 animals (8%) from two farms by HCl-pepsin digestion. The highest number of larvae per gram of muscle was found in the front limb muscles. Larvae of the 21 isolates have been identified as Trichinella britovi or Trichinella nativa by a multiplex-PCR analysis.

Animals↗
PubMed2006

Immunophenotypic characterization of peripheral blast cells in a leukemic miniature pig.

The health status of a 4-year-old female, dd-haplotype miniature pig deteriorated rapidly, so the animal finally had to be euthanized because of poor clinical condition. Necropsy revealed a massive leukocytic infiltration in the parenchymatous organs of the abdominal cavity. On hematologic cell counting, severe leukocytosis (69.3 x 10(9) cells/liter) and high-grade basophilia (6.9 x 10(9) cells/liter) were evident. Cytologic examination, as well as analysis of expression of leukocyte differentiation antigens by means of flow cytometry, classified blasts, which accounted for about 22% of leukocytes, as biphenotypic cells co-expressing the myeloid marker SWC3 (CD172a) and the lymphoid markers CD5 and CD25. Hematologic features resembled those seen in humans with chronic myeloid leukemia at blast phase.

Animals↗
PubMed2005

Structural analysis of a set of proteins resulting from a bacterial genomics project.

The targets of the Structural GenomiX (SGX) bacterial genomics project were proteins conserved in multiple prokaryotic organisms with no obvious sequence homolog in the Protein Data Bank of known structures. The outcome of this work was 80 structures, covering 60 unique sequences and 49 different genes. Experimental phase determination from proteins incorporating Se-Met was carried out for 45 structures with most of the remainder solved by molecular replacement using members of the experimentally phased set as search models. An automated tool was developed to deposit these structures in the Protein Data Bank, along with the associated X-ray diffraction data (including refined experimental phases) and experimentally confirmed sequences. BLAST comparisons of the SGX structures with structures that had appeared in the Protein Data Bank over the intervening 3.5 years since the SGX target list had been compiled identified homologs for 49 of the 60 unique sequences represented by the SGX structures. This result indicates that, for bacterial structures that are relatively easy to express, purify, and crystallize, the structural coverage of gene space is proceeding rapidly. More distant sequence-structure relationships between the SGX and PDB structures were investigated using PDB-BLAST and Combinatorial Extension (CE). Only one structure, SufD, has a truly unique topology compared to all folds in the PDB.

Databases, Protein↗
PubMed2005

Redox options in two-dimensional electrophoresis.

Two-dimensional electrophoresis is usually run on fully reduced samples. Under these conditions even covalently bound oligomers are dissociated and individual polypeptide chains may be fully unfolded by both, urea and SDS, which maximizes the number of resolved components and allows their pI and M(r) to be most accurately evaluated. However, various electrophoretic protocols for protein structure investigation require a combination of steps under varying redox conditions. We review here some of the applications of these procedures. We also present some original data about a few related samples -- serum from four species: Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus -- which we run under fully unreduced and fully reduced conditions as well as with reduction between first and second dimension. We demonstrate that in many cases the unreduced proteins migrate with a better resolution than reduced proteins, mostly in the crowded 'alpha-globulin' area of pI 4.5-6 and M(r) 50-70 kDa.

Animals↗
PubMed2005

Ligula intestinalis infection as a potential source of bias in the bioindication of endocrine disruption in the European chub Leuciscus cephalus.

European chub Leuciscus cephalus collected from five localities in the lowland and subalpine regions of Austria were analysed for oestrogenic effects of endocrine-disrupting chemicals and the presence of the plerocercoid of the tapeworm Ligula intestinalis. Of 1494 chub analysed, only seven (six males, one female) were found to be infected with single, but large plerocercoids up to 15 cm in length. Ligula-infected fish showed comparatively immature gonads, as demonstrated by the gonadosomatic index and gamete developmental stages. Plasma levels of the egg precursor protein vitellogenin also showed concentrations ranging below the detection limit. The present results indicate that chub infected with L. intestinalis and exposed to exogenous oestrogenic compounds can result in reduced gonadal maturation and produce false oestrogen-positive diagnoses in male fish. For plasma vitellogenin levels, L. intestinalis infections can result in false oestrogen-negative diagnoses in male and female fish.

Animals↗
PubMed2005

Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.

Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix proteins, were investigated by means of immunohistochemistry on uterine biopsies of healthy mares and animals with endometrosis. It was illustrated that both proteins were present in fibrotic regions of affected endometria, and that they were in most cases colocalized. Periglandular MMP-2 expression was significantly associated with dilated and fibrotic uterine glands. Furthermore, MMP-2 and TG 2 were demonstrated in the stratum compactum of healthy and endometrotic endometria. Gelatin zymography proved that active and inactive pro-form of MMP-2 were present in all examined samples with significantly higher amounts of total and active MMP-2 in affected endometria. TG 2-activity, determined by an in situ assay, was found in cases of severe periglandular fibrosis. We suggest that both enzymes play a major role in changes that occur in ECM homeostasis in endometrial fibrotic regions.

Animals↗
PubMed2004

The ultrasonically activated scalpel versus bipolar diathermy for tonsillectomy: a prospective, randomized trial.

Among patients undergoing tonsillectomy, the ultrasonic scalpel has been reported to lead to less intraoperative blood loss than cold dissection, and less postoperative pain and faster recovery than monopolar electrocautery. However, the ultrasonic scalpel has not been compared with bipolar diathermy. The present study was a prospective, randomized, single-blind trial, comparing these two techniques with respect to postoperative pain. Twenty-one adults underwent tonsillectomy on one side using the ultrasonic scalpel, and on the other using bipolar diathermy. Pain scores were obtained on postoperative days 1, 2, 7 and week 3. There was no difference between the two treatments at any of the time points (P = 0.6047, 0.4018, 0.6047 and 0.5000, respectively). Inability to control bleeding with the ultrasonic scalpel resulted in the rescue use of an alternative technique of haemostasis in 14 cases. We conclude that the use of the ultrasonic scalpel in adult tonsillectomy is likely to be limited by its substantial costs and difficulties with haemostasis.

Adolescent↗
PubMed2004

Clinical and pathological features of the Porcine Ulcerative Dermatitis Syndrome (PUDS).

The nomenclature of ulcerative dermatitis as used in literature is somehow confusing because on the one hand this skin disorder is associated with bacterial growth and on the other hand it is a synonym for a chronic sporadic disease of adult sows with unknown aetiology. Thus, we propose the terminus 'Porcine Ulcerative Dermatitis Syndrome (PUDS)' for the latter to distinguish between these two disease complexes. This syndrome could be identified by clinical and pathological examinations in six sows, that were submitted to the clinic. Epidermal ulcers could be found nearly all over the body, but teats were always spared. Haematological examination showed a slight anaemia but physiological leucocyte counts. However, lymphopenia (x = 44.8%), granulocytosis (x = 42.0%) and an increased number of monocytes (x = 13.1%) could be found. Histologically, a lymphoplasmacytic and granulohistiocytic infiltration in the corium was most prominent. In some cases, a moderate leucocytoclastic vasculitis and perivasculitis could be seen at the dermo-epidermal border. Additionally, a multifocal interstitial nephritis with lymphoplasmacytic infiltration was a prominent feature in all animals. Participation of an immune complex associated disorder can be assumed when regarding histological findings as skin lesions in combination with glomerulonephritis are a common feature of such diseases. Also, IgG levels were elevated two- to fourfold in all affected sows when compared with healthy control pigs. This supports the hypothesis that not only T cells, as shown previously, but also the humoral branch of the immune system is involved in the aetiology of PUDS.

Animals↗
PubMed2004

Hypothyroid goitre in a ram: chemical analysis gives indirect evidence for a structurally altered type of ovine thyroglobulin.

The thyroglobulin of a ram of the East Friesian milk sheep breed suffering from goitre was investigated by physico- and immunochemical methods. The respective ram was the only animal amongst the other sheep of the flock, that exhibited severe goitre, additionally showing depressed behaviour. Results of the thyroid-stimulating hormone response test were indicative of hypothyroidism. The dysfunction of the thyroid gland could be treated by additional iodine supplementation quite successfully, although all sheep had been given iodinated cattle salt throughout the course of the history. Without reducing conditions sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of isolated thyroglobulin molecules of the ram and control sheep did not reveal different band patterns, but under reducing conditions different band patterns were evident for the respective animals: the ram's thyroglobulin displayed two main bands, those of healthy reference sheep only one. Both bands reacted equally with anti-thyroglobulin antibodies, even with those produced by immunizing rabbits with single bands. The reduced single thyroglobulin band of healthy sheep corresponded to a truncated form of that molecule, whereas the additional main band of the ram was a more resistant, intact thyroglobulin subunit, as was shown by mass spectrometry. In conclusion, results of physico- and immunochemical investigations gave evidence of a modification of thyroglobulin with suspected different iodine binding properties in the ram. The latter finding may have clinical relevance in similar cases in other species, as it is an example of the impact that a minor change in a protein molecule may have on a complete metabolic pathway. Additionally, it could be shown, that in the ovine species the generally found single main band of thyroglobulin after reduction is a truncated form and not an intact subunit. This truncation seems to be induced in vitro by the reductive sample pretreatment prior to SDS-PAGE.

Animals↗
PubMed2002

Expression and characterization of functional recombinant bovine follicle-stimulating hormone (boFSHalpha/beta) produced in the milk of transgenic rabbits.

Bovine follicle-stimulating hormone (boFSH) is a heterodimeric glycoprotein that belongs to the pituitary gonadotropins. Bioactive FSH is composed of alpha and beta subunits which require extensive N-glycosylation and sialylation. The mammary gland of transgenic livestock is an attractive source for the synthesis of post-translationally modified proteins. Two mammary gland-specific gene constructs with the cDNA for the boFSH alpha (boFSHalpha) and beta (boFSHbeta) subunits controlled by bovine alpha-s1 casein regulatory sequences were co-microinjected into fertilized rabbit oocytes. Two FSHalpha/FSHbeta double transgenic rabbit lines were established. The transgene expression was strictly lactation and mammary gland specific. Protein analysis revealed the presence of the boFSH heterodimer in the milk of transgenic rabbits showing a molecular weight similar to that of purified pituitary gland derived boFSH (boFSH-P). Subunit specific antibodies detected both polypeptides with the expected molecular sizes. Biochemical characterization demonstrated the expected isoelectric points of the recombinant boFSH. The presence of the post-translationally added terminal sialic acid residues was indicated by wheat germ agglutinin (WGA) lectin Western blotting. The biological activity of the recombinant mammary gland produced boFSH was determined using a FSH-dependent reporter cell line. The bioactivity of the recombinant boFSH was comparable to that of purified boFSH-P.

Animals↗
PubMed2002

Breast cancer in women aged 35 and under: prognosis and survival.

BACKGROUND: Breast cancer comprises 22% of all cancers occurring in females but only 2% of cases occur in women aged 35 years and less. The presentation, behaviour and prognosis of breast cancer in such women, when compared with older women, are unclear and conflicting results have been reported. This study has audited clinical and pathological features in patients aged 35 years and under with breast cancer. METHODS: One hundred and thirteen patients were identified. The details of clinical staging, local and distant disease recurrence and overall survival were obtained for all patients. Histological sections of tumours were examined for type, grade, size, presence of surrounding intraductal carcinoma, presence of vascular space invasion, lymph node involvement and oestrogen receptor (ER) status. RESULTS: Histological examination of the tumours revealed that 94% were invasive ductal carcinoma. In 73% of the cases the tumours were grade 3, 49% of patients who underwent axillary surgery had lymph node involvement and 20% of tumours expressed ERs. The overall 5-year survival was 64%. Predictors of a poorer survival (univariate analysis) were: increasing tumour size, absence of ERs, presence of lymphovascular space invasion, axillary lymph node involvement and detectable metastases at the initial presentation. Multivariate analysis revealed that only lymphovascular space invasion was an independent predictor of a poor survival. CONCLUSION: Breast cancer in young (< or = 35 years) women is biologically aggressive, compared with older women. Factors predicting survival and overall survival rates, however, were comparable with those previously reported for older women with breast cancer.

Adult↗
PubMed2001

Proteins of rat serum, urine, and cerebrospinal fluid: VI. Further protein identifications and interstrain comparison.

We have investigated the biological fluids--serum, cerebrospinal fluid, and urine--of three strains of rats; the present data extend our database (also available on-line) and may be of interest for pharmacological and toxicological investigation. Specifically, we have defined reference maps of the major protein components in cerebrospinal fluid and urine. Compartment-specific isoforms were recognized for transferrin and transthyretin. Mass spectrometric data established the cleavage site of the signal peptide and identified the N-terminal blocking group of prostaglandin D synthase from rat cerebrospinal fluid. A previously undescribed member of the family of low molecular mass rat urinary proteins was characterized as containing a sequence similar, but not identical, to the N-terminal region of rat urinary protein-2 (RUP-2), and divergent from RUP-1.

Amino Acid Sequence↗
PubMed2001

Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups.

INTRODUCTION: While the short-term response rates to antidepressant medication and placebo are well established, very little is known about the short-term course of untreated depression. Knowledge of the course of untreated depression can serve as a benchmark for assessing the true benefits of active treatment. METHOD: A meta-analysis was performed analyzing the outcomes of all psychotherapy studies that randomized adult outpatients with major depressive disorder to a wait-list control group. RESULTS: Nineteen studies involving 221 subjects were reviewed. The mean decrease in Hamilton Rating Scale for Depression scores over 2-20 weeks was 11.9%, while the mean decrease in Beck Depression Inventory scores was 15.7%. Using a subsample of studies that reported individual outcomes, we estimated that 15 of 76 subjects (19.7%) improved to a degree comparable to what would be considered a positive response in antidepressant trials. CONCLUSIONS: In the short-term, depressive symptomatology can be expected to decrease by about 10-15% on average without treatment. As many as 20% of subjects who participate in a short-term antidepressant trial may experience a spontaneous remission.

Adult↗
PubMed2001

IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy.

Abnormalities of chromosome 1q21 are common in B cell malignancies, but their target genes are largely unknown. By cloning the breakpoints of a (1;14) (q21;q32) chromosomal translocation in a myeloma cell line, we have identified two novel genes, IRTA1 and IRTA2, encoding cell surface receptors homologous to the Fc and inhibitory receptor families. Both genes are selectively expressed in mature B cells: IRTA1 in marginal zone B cells and IRTA2 in centrocytes, marginal zone B cells, and immunoblasts. As a result of the t(1;14), IRTA1 is fused to the immunoglobulin Calpha domain to produce a chimeric IRTA1/Calpha fusion protein. In tumor cell lines with 1q21 abnormalities, IRTA2 expression is deregulated. Thus, IRTA1 and IRTA2 are novel immunoreceptors implicated in B cell development and lymphomagenesis.

Amino Acid Sequence↗
PubMed2001

Caseload in rural general surgical practice and implications for training.

BACKGROUND: Despite increasing specialization within general surgery, many general surgeons, particularly in rural practice, continue to treat a wide range of conditions. The aim of the present paper was to provide accurate information on three rural surgeons' case-loads to illustrate the spectrum of surgery encountered and to assist in the planning of rural general surgical training. METHODS: A review was conducted of a prospectively maintained database of operations performed by three rural general surgeons in different parts of Victoria, Australia over a 5-year period. RESULTS: A large volume and wide range of procedures was performed by each surgeon, who averaged more than 500 operations per year (excluding endoscopies). Although most were within the range of procedures covered in the Royal Australasian College of Surgeons (RACS) Fellowship in general surgery, some encroached upon other specialties such as orthopaedics, urology, paediatric surgery and obstetrics/gynaecology. Operations outside of 'general' surgery reflected individual training and local community needs. CONCLUSIONS: The current RACS Fellowship in general surgery, augmented by training in other specialties as required, will help prepare general surgeons for rural practice.

Curriculum↗