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Biomedical subjects

A Higgins

Publications and source records attributed to A Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1993

Enzyme replacement with recombinant beta-glucuronidase in the newborn mucopolysaccharidosis type VII mouse.

beta-Glucuronidase injected i.v. into newborn mucopolysaccharidosis VII mice was cleared from the circulation in less than 1 h and taken up by tissues in a distribution corresponding to the location of the mannose 6-phosphate receptor. One h after a 3.5-mg/kg beta-glucuronidase injection, beta-glucuronidase levels were equal to or greater than normal in every organ examined with the exception of the brain, where 31% normal activity was present. Enzyme was detectable histochemically in the major sites of pathology for mucopolysaccharidosis VII including bone, brain, heart, and fixed tissue macrophages. The half-life of recombinant beta-glucuronidase activity in various organs of injected mucopolysaccharidosis VII mice was 1.5 to 4.5 d. These studies show that recombinant beta-glucuronidase administered to newborn mice reaches the sites of clinically important storage in murine mucopolysaccharidosis VII.

Animals↗
PubMed1993

Is bradykinin (BK) a physiological vasodilator in the gut?

The physiological role of bradykinin (BK) as a mesenteric vasoregulator was explored. This nonapeptide is a potent vasodilator substance when administered exogenously in multiple in vivo models and is a smooth muscle relaxant when added to in vitro preparations. BK is naturally occurring in the gut wall. The substrate for BK, as well as the biosynthetic and metabolizing systems are present in the blood, the vascular wall, immunological cells, and perivascular neurons. BK B2 and B1 receptors have been characterized with sympathetic agonist and antagonist substances, and the receptors are present on mesenteric endothelial cells and myocytes. BK interacts with multiple endogenous mesenteric vasodilator mediators, such as nitric oxide, prostacyclin, and neuropeptides. Taken together this evidence supports the functional importance of BK as a normal vasodilator in the gut.

Amino Acid Sequence↗
PubMed1991

Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.

Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.

Anemia, Hemolytic↗
PubMed1990

Lithium clearance in healthy humans: effects of sodium intake and diuretics.

In summary, our experiments clearly demonstrate that lithium reabsorption occurs by frusemide- and bumetanide-sensitive reabsorption, but we have failed to identify the mechanism(s) responsible for the lower CLi and FELi in salt-depletion. It is possible that some, as yet unknown, factor increases the activity of the Na, K, 2Cl cotransporter and, hence, increases lithium reabsorption in the thick ascending limb in salt-depleted subjects. However, it is equally possible that a fraction of proximal tubular reabsorption is inhibited by frusemide and bumetanide. If this is correct, CLi in humans are reasonable markers of proximal tubular function even in conditions of avid salt retention and in salt depletion, when fractional reabsorption of salt and water in the proximal tubules is enhanced.

Amiloride↗
PubMed1989

Evaluation of enzyme immunoassays in the diagnosis of camel (Camelus dromedarius) trypanosomiasis: a preliminary investigation.

Three enzyme immunoassays were used for the serodiagnosis of Trypanosoma evansi in camels in the Sudan in order to evaluate their ability to discriminate between infected and non-infected animals. Two assays were used for the detection of trypanosomal antibodies, one using specific anti-camel IgG conjugate and another using a non-specific Protein A conjugate. The third assay detected the presence of trypanosomal antigens using anti-T. evansi antibodies in a double antibody sandwich assay. Inspection of the frequency distribution of assay results suggested that the ELISA for circulating trypanosomal antibodies using specific antisera and the ELISA for circulating antigens can distinguish between non-infected camels and infected camels exhibiting patent infections or not. The ELISA using Protein A conjugate to bind non-specifically to camel immunoglobulin did not appear to discriminate between infected and non-infected animals.

Animals↗
PubMed1988

High resolution on-line analysis of cardiac action potentials using a Motorola 68000 microcomputer.

We have developed a microcomputer system for the instantaneous on-line analysis of cardiac action potentials (APs) based on a Motorola 68000 microprocessor and 50 kHz A/D converter. This system can accurately analyze APs from all parts of the heart, including the extremely fast upstrokes of APs from Purkinje fibers. Facilities for tabulation of results, production of hard-copy plots of APs, pooling of experimental data, and statistical analyses are available off-line. The routine use of this system in our laboratory has greatly increased the accuracy and throughput of these time-consuming experiments.

Action Potentials↗
PubMed1988

FMRFamide prevents habituation and potentiates the gill withdrawal reflex in the isolated gill preparation of Aplysia.

Perfusion of the endogenous neuropeptide, FMRFamide, through the isolated gill of Aplysia facilitated the amplitude of the gill withdrawal reflex (GWR) evoked by tactile stimulation of the gill. The GWR was facilitated in a dose-dependent manner. The facilitation of the GWR produced by FMRFamide perfusion was reversible. In addition to facilitating GWR amplitude, FMRFamide perfusion could also prevent habituation of the reflex. It is hypothesized that FMRFamide may play a role in the peripheral nervous system (PNS) in the gill in the mediation of behavioral state and modulation of adaptive gill behaviors.

Animals↗
PubMed1988

Loss of Crown Immunity: general implications for local authorities and district health authorities.

In August 1984, 355 patients and 106 staff at the Stanley Royd Hospital in Wakefield were involved in an outbreak of food poisoning as a result of which 19 died. The inquiry following publicised, if not sensationalised the outbreak, found that there had been a complete failure to follow the basic rules of food hygiene practice which was not assisted by the condition and inadequacies of the kitchen, the environment in which the staff had to work or the tools and equipment they had to use. The inquiry also noted that just as it is possible to avoid food poisoning in a bad kitchen it is possible for it to arise from faulty hygiene in the most suitable of premises.

England↗
PubMed1987

Fetal breathing movements are not a reliable predictor of continued lung development in pregnancies complicated by oligohydramnios.

Fetal breathing activity was monitored by ultrasonography in 14 patients with oligohydramnios (4 with fetal anuria and 10 with premature rupture of the membranes). 45 patients with intact membranes, with normal amniotic fluid volume, and matched for gestational age were the controls. Fetal breathing movements were seen in all 8 patients who died in the perinatal period with a necropsy diagnosis of lung hypoplasia. While patients with premature rupture of the membranes (irrespective of outcome) spent the same or less time breathing than controls, fetuses with renal anomalies, oligohydramnios, and lung hypoplasia spent more time breathing than controls. The observation of fetal breathing activity is not helpful in identifying patients with oligohydramnios at risk of lung hypoplasia.

Amniotic Fluid↗
PubMed1987

MHC antigen expression in sequential biopsies from cardiac transplant patients--correlation with rejection.

Class I induction on the myocardium of transplanted heart was investigated with regard to its temporal relationship to rejection episodes, how it is affected by anti-rejection therapy and whether it is dependent upon the presence of a T cell infiltrate in the biopsy. Sequential cardiac biopsies (total 114) from 11 patients from the time of transplant to 1 year after transplant were studied using immunocytochemical techniques. The effect of different immunosuppressive regimens on MHC antigen expression was also studied. All the biopsies diagnosed as showing rejection for the first time showed induction of Class 1 on the myocardium with 79% during subsequent rejection episodes. Class I induction was associated with a leucocyte infiltrate, not always containing T cells, and disappeared in 47% of biopsies taken 3-4 weeks after treatment with steroids and/or ATG. Increased expression of Class II, in particular DQ antigens on interstitial structures, paralleled Class 1 induction. MHC antigen expression returned to normal in 8/9 patients, at 1 year after transplant. Different immunosuppressive regimens affected the number of biopsies showing Class 1 induction on the myocardium. Our results suggest that in clinical heart transplantation class I induction is related to the rejection process.

Adolescent↗
PubMed1987

OKT3-activated locomotion of human blood lymphocytes: a phenomenon requiring contact of T cells with Fc receptor-bearing cells.

The OKT3 antibody activates locomotion of human blood T lymphocytes as measured by polarization assays and invasion of collagen gels. The proportion of motile cells increases during a period of 24-48 hr of culture, even following only a brief initial contact with OKT3. The motile cells are the growing population. Locomotion activation is cell-density dependent. Studies with surface-bound mitogens, namely substratum-bound OKT3 and Con A-Sepharose, showed that only lymphocytes in direct contact with the mitogen acquired locomotor capacity. Those separated from it by a cell-impermeable filter were not activated. The response to OKT3 requires the whole antibody molecule. F(ab')2 fragments were inactive. Intact normal human IgG, but not its F(ab')2 fragments, blocked the response. Removal of RFc gamma + cells from the population by rosetting with IgG-Ab-coated sheep red cells prevented the response. These findings suggest that an RFc gamma + population has to be present for T cells to become activated to locomotion by OKT3, and that the OKT3 antibody links the T cell to an FcR+ cell, cell-to-cell contact being essential for activating the locomotor response.

Antibodies, Monoclonal↗
PubMed1987

Cyclosporin A inhibits mitogen-activated but not phorbol ester-activated locomotion of human lymphocytes.

Human blood lymphocytes acquire locomotor capacity during 24 hr culture with mitogens such as monoclonal anti-CD3 antibodies, phytohaemagglutinin (PHA), or Staphylococcus aureus Cowan strain (SAC). Activation of locomotor capacity by these agents is blocked by the presence of cyclosporin A (greater than or equal to 10 ng per ml), as measured by inhibition of the development of morphological polarization of the cells in culture and inhibition of their capacity to invade collagen gels. The response to OKT3 is inhibited by lower doses of cyclosporin than the responses to SAC or PHA. Phorbol myristate acetate (PMA) induces locomotion of lymphocytes in culture that is not inhibited by cyclosporin. Cyclosporin has no effect on the locomotion of lymphocytes that already possess locomotor capacity. Thus it neither inhibits immediate stimulus-induced polarization of lymphocytes direct from blood, nor reverses polarization of lymphocytes that have acquired motility in culture. These results suggest that cyclosporin prevents events, occurring during the G1 phase of growth, that are necessary for non-motile lymphocytes to acquire locomotor capacity, but has no effect on the locomotor mechanism itself in already motile cells.

Antibodies, Monoclonal↗
PubMed1984

The efficacy of drug delivery by a pear-shaped spacer and metered dose inhaler.

The efficacy of terbutaline delivered via a 750 ml spacer device (Nebuhaler) compared with a metered dose inhaler alone was studied by means of an open cross-over trial in eight patients with stable asthma. The FEV1 and FVC response curves with cumulative doses up to 8 mg were shifted significantly to the left using the device, whilst side effects were not significantly increased. These results indicate that the spacer significantly improves aerosol drug delivery from a pressurized inhaler, even in patients whose inhalation technique was considered adequate.

Adult↗