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Biomedical subjects

M Ware

Publications and source records attributed to M Ware.

15 recordsLinked to original sources
PubMed1999

X-chromosome inactivation patterns do not implicate asymmetric splitting of the inner cell mass in the aetiology of twin-twin transfusion syndrome.

The aetiology of twin-twin transfusion syndrome (TTTS) is unclear. We investigated the hypothesis that monochorionic (MC) pregnancies with TTTS are associated with differences in the timing and symmetry of twinning compared to MC twin pregnancies without TTTS. DNA was extracted from the umbilical cord vessels of 26 female MC twins, 14 with and 12 without TTTS on serial antenatal ultrasound. X-inactivation patterns were determined by DNA digestion with Hhal and Hpall followed by polymerase chain reaction for a polymorphic trinucleotide repeat in the androgen receptor gene. Products were quantified by densitometry and results compared to those in peripheral blood samples of adult female controls. The median degree of non-random inactivation was similar in MC twins with TTTS, in MC twins without TTTS, and in adult controls. The percentage of individuals with skewed (> or =30/70%) inactivation patterns was no different in MC twins with TTTS compared to those without TTTS, and was similar to adult controls using either enzyme technique. In conclusion we found no difference in the degree or frequency of non-random X-inactivation patterns in TTTS. X-inactivation patterns do not appear to be a useful tool for studying the symmetry of inner cell mass splitting in monochorionic twins.

Adult↗
PubMed1997

SHIP, a new player in cytokine-induced signalling.

We recently purified and cloned the cDNAs for the murine and human forms of a novel 145 kDa inositol polyphosphate 5-phosphatase (5-ptase) that becomes tyrosine phosphorylated and associated with Shc following stimulation of hemopoietic cells with multiple cytokines. Unlike most 5-ptases which hydrolyze phosphatidylinositol-4,5-P2-bisphosphate (PI-4,5-P2) and/or inositol-1,4,5-trisphosphate (I-1,4,5-P3), this enzyme selectively hydrolyzes the 5'-phosphate from inositol-1,3,4,5-tetraphosphate (I-1,3,4,5-P4) and phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3), two inositol polyphosphates recently implicated in growth factor-mediated signalling. This 5-ptase is also unique among 5-ptases in that it is the only one to date to possess an SH2 domain. In this review we discuss the cloning, the Shc binding and the potential role of this protein, which we call SHIP, for SH2-containing inositol 5-phosphatase, in cell proliferation, differentiation and apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Numerical representations in primates.

Research has demonstrated that human infants and nonhuman primates have a rudimentary numerical system that enables them to count objects or events. More recently, however, studies using a preferential looking paradigm have suggested that preverbal human infants are capable of simple arithmetical operations, such as adding and subtracting a small number of visually presented objects. These findings implicate a relatively sophisticated representational system in the absence of language. To explore the evolutionary origins of this capacity, we present data from an experiment with wild rhesus monkeys (Macaca mulatta) that methodologically mirrors those conducted on human infants. Results suggest that rhesus monkeys detect additive and subtractive changes in the number of objects present in their visual field. Given the methodological and empirical similarities, it appears that nonhuman primates such as rhesus monkeys may also have access to arithmetical representations, although alternative explanations must be considered for both primate species.

Animals↗
PubMed1996

Molecular genetic etiology of twin reversed arterial perfusion sequence.

OBJECTIVE: Our purpose was to determine whether the twin reversed arterial perfusion sequence (acardiac anomaly) results from fertilization of the first or second polar body. STUDY DESIGN: Placental or fetal tissue was obtained from nine twin sets discordant for twin reversed arterial perfusion. After deoxyribonucleic acid extraction, the polymerase chain reaction was used to amplify five polymorphic microsatellite repeats. The products were differentiated by polyacrylamide gel electrophoresis, and patterns were compared within twin sets. RESULTS: Deoxyribonucleic acid fingerprinting patterns were identical in all twin sets for all primer pairs. It is calculated that the chance that any of the acardiac twins resulted from fertilization of either the first or second polar body is <4% and the chance that they all resulted from polar body fertilization is <0.001%. CONCLUSION: Twins discordant for the twin reversed arterial perfusion sequence anomaly are monozygous. Our results exclude polar body fertilization as a likely cause of this condition.

Autoradiography↗
PubMed1994

Increased neuropeptide Y concentrations in specific hypothalamic regions of lactating rats: possible relationship to hyperphagia and adaptive changes in energy balance.

Lactation is accompanied by hyperphagia and a reduction in brown adipose tissue (BAT) thermogenesis, which are unexplained. Neuropeptide Y (NPY) powerfully stimulates feeding and inhibits BAT thermogenesis when injected into the paraventricular nucleus and other specific regions of the rat hypothalamus. We have tested the hypothesis that hypothalamic NPY activity is increased in lactating rats. Lactating rats consumed over four times as much food as nonlactating controls (n = 10; p < 0.001). Final plasma insulin concentrations in lactating rats were lower than in controls (6.8 +/- 0.8 vs. 11.7 +/- 2.1 pmol/l; p < 0.05) although plasma glucose and corticosterone concentrations were comparable (p > 0.05). Lactating rats showed significantly higher NPY levels than controls in specific hypothalamic regions, namely the arcuate nucleus-median eminence complex (a 41% rise; p < 0.001), paraventricular nucleus (35%; p < 0.001), ventromedial nucleus (66%; p = 0.003), and dorsomedial nucleus (78%; p < 0.001). Other hypothalamic regions showed no significant differences between groups. Increased NPY concentrations in specific hypothalamic regions, particularly the arcuate nucleus where NPY is synthesized, suggest increased activity of the hypothalamic NPYergic system in lactation. Neuropeptide Y may mediate hyperphagia and reduced BAT thermogenesis in lactation. Hypoinsulinemia may be a stimulus to hypothalamic NPY in lactation, as has been postulated in other conditions of negative energy balance.

Adaptation, Physiological↗
PubMed1992

Effects of dietary protein deficiency on mineral metabolism and bone mineral density.

The effects of dietary protein restriction on mineral and bone metabolism are uncharacterized. We studied growing rats fed a diet low in protein (5%) for 4, 6, and 8 wks (n = 10 animals/group) and compared them with animals pair-fed with a protein-replete (18%) diet. The low-protein diet rapidly induced a profound hypocalciuria that persisted for greater than or equal to 8 wk. Serum calcium and phosphorus concentrations were not affected but serum total and free 25-dihydroxyvitamin D concentrations as well as gastrointestinal calcium absorption were lower in the low-protein animals. Skeletal dimensions were reduced in the protein-deprived rats but there were no significant differences in bone mineral content between control and low-protein animals at 4, 6, and 8 wks. Hence, dietary protein deprivation resulted in slower growth but bone mineral density was maintained when there was a marked reduction in urinary calcium excretion.

Animals↗
PubMed1983

Combination estrogen and progestogen replacement therapy does not adversely affect coagulation.

Coagulation and fibrinolysis profiles of naturally menopausal women receiving conjugated estrogens (0.625 or 1.25 mg for 21 of 28 days) and medroxyprogesterone acetate (10 mg for seven of 28 days) for 18 months were compared with those of similar women receiving no hormone therapy. Tests indicative of the dynamics of the coagulation cascade, ongoing intravascular coagulation, and anticoagulation were performed. Hormone therapy had no effect on prothrombin times, activated partial thromboplastin times, or thrombin times. There was no evidence of intravascular coagulation in any of the groups as assessed by platelet counts, fibrinogen antigen and activity, and fibrin degradation products. Antithrombin III antigen and activity, alpha 1-antitrypsin antigen, and alpha 2-macroglobulin antigen, the natural inhibitors of coagulation, were also unaffected by hormone therapy. Plasminogen antigen levels were unaffected, but plasminogen activity was enhanced in the hormone-treated groups, suggesting a stimulatory effect on fibrinolysis. These data indicate that in terms of the coagulation system, healthy women can safely use a combined regimen of conjugated estrogens and medroxyprogesterone acetate.

Androstenedione↗
PubMed1979

The short term distribution of thiopentone in the dog.

Rapid sampling of arterial blood following intravenous infusion of thiopentone at various speeds has demonstrated that the peak concentrations for doses given over five seconds are at least twice those for doses given over fifteen seconds. The area under the curves and the dispersed arterial concentrations show no significant difference between infection speeds.

Animals↗
PubMedDate not supplied

Increased neuropeptide Y concentrations in specific hypothalamic nuclei of the rat following treatment with methysergide: evidence that NPY may mediate serotonin's effects on food intake.

Neuropeptide Y (NPY) is a potent central appetite stimulant found in hypothalamic neurons that have close anatomical associations with neurons containing serotonin, a powerful anorectic agent. To determine whether the two neurotransmitters interact functionally, we have studied the effects on regional hypothalamic NPY concentrations of acute and chronic administration of methysergide, a 5-HT1BC/serotonin receptor antagonist. Chronic methysergide treatment (10 mg/kg/day) was given by subcutaneously implanted osmotic minipumps (n = 8). Acute effects of methysergide were determined 4 h after a single injection (10 mg/kg) in a separate group (n = 8). Controls (n = 8) had implanted minipumps delivering saline, and also received a saline injection 4 h before sacrifice. Food intake was significantly increased (p < 0.01) by both acute and chronic methysergide treatment. In the chronically treated rats, NPY levels were significantly increased over controls in the arcuate nucleus (ARC; by 41%, p = 0.02) and paraventricular nucleus (PVN; by 40%, p < 0.01). Acute methysergide treatment also increased NPY concentrations in the ARC (by 81%, p < 0.01) and PVN (by 30%, p < 0.01). Methysergide administration, which stimulated feeding, therefore raised NPY concentrations in the ARC, where NPY is synthesized, and in the PVN, a major site of NPY release where NPY injection induces hyperphagia. These findings suggest that NPYergic and serotoninergic innervations in the hypothalamus interact to regulate food intake, and raise the possibility that increased NPY release may mediate the hyperphagic effect of serotoninergic 5-HT1BC/receptor blockade.

Animals↗
PubMedDate not supplied

Lack of relationship between sympathetic nervous system activity, measured by two circulating markers, and blood pressure in diabetic and nondiabetic subjects.

Two putative sympathetic nervous system (SNS) markers, noradrenaline and neuropeptide Y (NPY) were related to 24-h ambulatory blood pressure (BP) in 59 normotensive subjects, 34 non-insulin-dependent diabetics, and 25 controls. Plasma NPY levels were not significantly different between the two groups [non-insulin-dependent (NIDDM) diabetes mellitus 4.33 (3.25-5.78), controls 5.68 (3.39-6.97) p=0.26] as were those of noradrenaline (1.51+/-0.69 versus 1.78+/-0.55; p=0.053). There were correlations, controlled for age and obesity, of plasma NPY with clinic and night time diastolic BP in the control group only (r=0.49 [p=0.013] and r=0.48 [p=0.023] respectively). No similar correlation was found in the NIDDM group, or between plasma noradrenaline and blood pressure in either group. No correlation was found between plasma insulin and NPY or noradrenaline levels. There is a weak independent relationship between NPY and blood pressure in normotensive nondiabetics but not in NIDDM subjects. We found no evidence for the hypothesis that insulin modulates blood pressure through activity of the SNS.

Adult↗