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Biomedical subjects

M Vickers

Publications and source records attributed to M Vickers.

At least 19 recordsLinked to original sources

Growth hormone treatment of breeding bulls used for artificial insemination improves fertilization rates.

To evaluate new therapeutical concepts for male subfertility, we tested the effects of exogenous recombinant bovine growth hormone (rbGH) on various endocrine and metabolic parameters both in blood and in seminal plasma of bulls. Sperm quality was assessed morphometrically and by monitoring the number of successful artificial inseminations (AIs) defined as non-return rates (NRR). Aliquots of 450 semen samples were used from each bull and each experimental period (4 wk before, 14 weeks during and 6 wk after treatment). Six out of ten sires (average age 8.4 years) were treated every two weeks with 640-mg depot formulated rbGH (Eli Lilly). Four bulls received vehicle only. Blood plasma bGH, IGF-I, insulin and glucose concentrations were increased with rbGH treatment. In seminal plasma there was no effect of rbGH treatment on fructose and citrate or on testosterone concentrations. With one exception, rbGH-treated bulls had greater IGFBP-3 concentrations in seminal plasma. Motility of spermatozoa after freezing and thawing was increased compared with pretreatment rates. Most interestingly, the number of successful AIs was increased by an average of 6.0% NRR when ejaculates from rbGH-treated bulls were used.

Animals↗

The incidence of acute promyelocytic leukemia appears constant over most of a human lifespan, implying only one rate limiting mutation.

It is believed that most malignancies become more common with increasing age due to the requirement for several mutations to accumulate and subsequently interact. The age specific incidence of acute promyelocytic leukemia (APL) was investigated using population-based data from 77 million subject years of observation, yielding 149 consecutive cases. The incidence appears approximately constant with respect to age, an observation not previously reported with any other malignancy. These findings are most easily explained by there being only one rate limiting genetic event required to initiate the disease, although other, non-rate limiting mutations may also be necessary for disease development. It is also argued that this mutation is probably restricted to cells committed to differentiation, which may explain why APL is curable by chemotherapy.

Adolescent↗

Modelling haemopoietic stem cell division by analysis of mutant red cells.

Data describing the number of human red cells mutated at the glycophorin A locus, measured flow cytometrically, are reported for 752 adults and 49 neonates. The variance increases with age more rapidly than the approximately linear increase in mean. It is postulated that this discrepancy is explained by the known property of asymmetric stem cell division, so that the division of a single mutant stem cell may result in zero, one or two progeny stem cells. A mathematical analysis allows description of this process with three parameters: stem cell number, mean division rate and mutation rate per division. The values of these parameters can not be deduced from the data presented here. However, estimates of either stem cell number or mutation rate from other sources enable deduction of the two other parameters. The mean number of divisions per stem cell per lifetime was estimated to be about 70. This analysis therefore implies that the rate at which blood cell telomeres shorten with age acts as a direct measure of stem cell turnover. Furthermore, it is argued that this low figure implies that mutations occurring during early life, including organogenesis, are relatively important in initiating stem cell-derived malignancy. Finally, the number of human stem cell divisions per lifetime is similar to shorter-lived mammals, suggesting this number is important in the ageing process.

Adult↗

Ovulation induction with low dose alternate day recombinant follicle stimulating hormone (Puregon).

We investigated whether a recombinant follicle stimulating hormone (FSH) (Puregon) can be administered less frequently and at lower doses during ovulation induction than is current practice. Patients (20-35 years, body mass index <30 kg/m(2)) with infertility and chronic anovulation secondary to polycystic ovarian syndrome and resistant to previous clomiphene treatment received (Puregon); 100 IU, n = 17 patients, or 50 IU, n = 10 patients) on alternate days. After 2 weeks and in the absence of follicular recruitment, doses were increased stepwise at weekly intervals (50 IU/alternate days). Twenty-two cycles out of 27 were ovulatory. There were six pregnancies, five from Puregon (100 IU) and one from Puregon (50 IU); four pregnancies proceeded to term. The duration of stimulation (mean, range) with Puregon (100 IU) was 16.4, 7-29 and Puregon (50 IU) 19.1, 8-38 days. The gonadotrophin doses administered (mean; range) were 689, 200-1800 IU (Puregon 50 IU) and 939, 400-2300 IU (Puregon 100 IU). We conclude that low dose alternate day Puregon treatment is suitable for this difficult patient group.

Adult↗

Clinical examination for abdominal aortic aneurysm in general practice: report from the Medical Research Council's General Practice Research Framework.

At the time of the 1992-1994 annual reviews in the thrombosis prevention trial, general practitioners (GPs) carried out clinical examination for aneurysms by abdominal palpation in 4171 men. When an aneurysm was suspected, the patient was referred to hospital for further investigation. Aneurysm was suspected in 60 men (1.4%) and confirmed in 25 (0.6%), the mean diameter of confirmed aneurysms being 5.0 cm (range = 3.1-8.0 cm). Of the 25 men in whom aneurysm was confirmed, 10 (40%) underwent elective surgery and one died while under investigation. Examination by abdominal palpation for aortic aneurysm, which is not widely used in either general practice or in hospital practice, other than vascular surgery, is clinically worthwhile even though not all aneurysms will be detected by this means.

Aged↗

Functional complementation of a membrane transport deficiency in Saccharomyces cerevisiae by recombinant ND4 fusion protein.

ND4 is a mitochondrially encoded component of NADH dehydrogenase (Complex I) of the respiratory chain. A cDNA encoding a fusion protein comprised of the N-terminus of GAL10 of Saccharomyces cerevisiae and an N-terminally truncated form of human ND4 was isolated by its ability to functionally complement the thymidine transport deficiency of S. cerevisiae grown under conditions of thymidylate starvation. Epitope-tagged GAL10-ND4 was shown by immunological methods to be present in the plasma membranes of yeast expressing the GAL10-ND4 encoding cDNA. The ability of the GAL10-ND4 fusion protein to induce uptake of thymidine raises the possibility that native ND4, which is predicted to have 12 transmembrane domains, may function as a transporter or channel in the mitochondrial inner membrane.

Amino Acid Sequence↗

Insulin-like growth factors (IGFs) and IGF binding proteins, serum acid-labile subunit and growth hormone binding protein in nephrotic children.

We hypothesized that the increased glomerular permeability to serum proteins in the nephrotic syndrome might lead to alterations of the somatotropic hormone axis, thereby contributing to growth failure and catabolism in the nephrotic state. The insulin-like growth factors (IGF)-I and -II and the IGF binding proteins (IGFBP)-1, -2 and -3 were analyzed in serum and urine of 21 children with the nephrotic syndrome and normal glomerular filtration rate. Mean age-related serum IGF-I levels by RIA (-0.53 +/- 0.34 SD) were slightly, but significantly (P < 0.05) decreased compared with the reference population, whereas mean age-related serum IGF-II levels (0.68 +/- 0.21 SD) were slightly, but significantly (P < 0.005) increased. The urinary excretion rate of both peptides was enhanced fivefold. By RIA, mean age-related serum IGFBP-1 (2.05 +/- 0.19 SD) and, even more pronounced, IGFBP-2 (5.97 +/- 0.65 SD) were clearly elevated despite a 12-fold and 2-fold increase of the respective urinary excretion rate. There was a tight and specific correlation between age-related serum IGFBP-2 levels and the degree of the nephrotic syndrome, as estimated by serum albumin levels (r = -0.78, P < 0.0001). Serum immunoreactive IGFBP-3 levels were also elevated (1.79 +/- 0.33 SD) in nephrotic serum, due to an increase of low-molecular weight IGFBP-3 fragments. By FPLC analysis, there was a decrease of the 150 kDa IGFBP ternary complex in nephrotic serum, which in the presence of normal concentrations of the acid-labile subunit by RIA appears to be due to a reduction of intact IGFBP-3. Serum levels of the high-affinity GH binding protein that presumably reflects GH receptor status in tissues were normal. In summary, total serum IGFs in children with the nephrotic syndrome are normal, but the binding of IGFs to IGFBPs in the circulation is altered with a shift from the 150 kDa IGFBP complex to an excess of low molecular weight IGFBPs. Because increased unsaturated high-affinity IGFBPs in nephrotic serum have the ability to inhibit IGF action on target tissues by competing with the type 1 IGF receptor for IGF binding, this alteration is likely to contribute to growth failure and tissue catabolism in the nephrotic state.

Carrier Proteins↗

The development of patient information leaflets. Care of the mouth after radiotherapy.

OBJECTIVES: Describe the methodology used to produce a patient leaflet on care of the mouth after radiotherapy. DESIGN: Prospective study to design a patient information leaflet. SETTING AND SUBJECTS: Patients undergoing radiotherapy for oral cancer. INTERVENTION: After a review of the relevant literature, a patient questionnaire was produced. This was then completed by patients undergoing radiotherapy treatment and gave an indication of the problems being encountered. Healthcare professionals were surveyed for their views. A leaflet was then produced according to published guidelines. It was taken back to another group of patients and a further version produced after input from a health promotion group. RESULTS: A leaflet was produced after wide consultation and survey. CONCLUSIONS: Considerable effort must to be put into the production to patient information leaflet. It must be discussed with patients in the target group if it is to be sensitive, understood and find acceptance among its users.

Cranial Irradiation↗

The isolation and characterization of magnesium whitlockite crystals from human articular cartilage.

A number of basic calcium phosphate crystals have been demonstrated in human articular tissues. The exact relationship between crystal deposition and disease remains obscure, although there is evidence supporting a rapid degenerative arthropathy within a specific set of patients. Limited reports of 'cuboid' calcium phosphate microcrystals in articular cartilage have been made over the last 10 years. In this study the occurrence of such crystals, not apparent by light microscopy, in human articular cartilage has been confirmed by transmission electron microscopy and X-ray microanalysis of tissue prepared by aqueous and anhydrous processing techniques. A crystal isolation technique involving collagenase digestion, centrifugation and sodium hypochlorite treatment was developed enabling crystal characterization by electron and X-ray diffraction. Crystals were identified as magnesium whitlockite; the first report of this mineral in articular cartilage. The presence of this mineral phase in normal and osteoarthritic articular cartilage is discussed with consideration given to physical conditions known to favor whitlockite formation and those extant in articular cartilage.

Calcium Phosphates↗