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Biomedical subjects

M W Ho

Publications and source records attributed to M W Ho.

At least 37 records · Page 2Linked to original sources

Ins(3,4,5,6)P4 specifically inhibits a receptor-mediated Ca2+-dependent Cl- current in CFPAC-1 cells.

We have examined the role of inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P4] in the control of Cl- current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P4 had no effect on basal current, but it produced a five- to sevenfold reduction in the Cl- current stimulated by either 2 microM extracellular ATP or by 1 microM extracellular thapsigargin. The half-maximally effective dose of Ins(3,4,5,6)P4 was 2.9 microM, and 4 microM blocked >80% of the ATP-activated current. In contrast, 10 microM Ins(1,4,5,6)P4, Ins(1,3,4,5)P4, or Ins(1,3,4,6)P4 enhanced rather than inhibited the ATP-activated Cl- current, although Ins(1,4,5,6)P4 only acted transiently. These stimulatory effects were Ca2+ dependent and largely inhibited by coapplication of equimolar Ins(3,4,5,6)P4. Inositol 1,3,4,5,6-pentakisphosphate, the precursor of Ins(3,4,5,6)P4, did not affect Cl- current. These data consolidate and extend the hypothesis that Ins(3,4,5,6)P4 is an important intracellular regulator of Cl- current in epithelial cells.

Adenosine Triphosphate↗

Evidence that channels below 1 pS cause the volume-sensitive chloride conductance in T84 cells.

The volume-activated chloride current of T84 human colonic cells was studied using the whole-cell patch clamp. The current appeared reliably with a mild osmotic gradient and in the absence of intracellular ATP. It reversed at the chloride equilibrium potential and was blocked by the chloride channel blocker DIDS. Development of the current was accompanied by an increase in the current noise variance, typical of increasing ion channel open probability. Noise variance was always well-fitted by a double Lorentzian relationship with corner frequencies at approximately 1.7 Hz and approximately 60 Hz. The increase in variance during development of the volume-sensitive current was mostly due to an increase in the high frequency component. The relationship between noise variance and membrane current was well-fitted by a relationship with a single channel conductance of approximately 0.2 pS.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Comparison of prostaglandin E2 vaginal tablet with amniotomy and intravenous oxytocin for induction of labour.

Prostaglandins have been increasingly used in obstetrical practice for cervical ripening and induction of labour. We set out to investigate the effectiveness of prostaglandin E2 (PGE2) vaginal pessaries in inducing labour in the Chinese population in Hong Kong. In the period August, 1991 to August, 1992, we recruited 206 pregnant Chinese women who required induction of labour for various obstetrical indications into the trial. The study group had induction of labour by PGE2 vaginal pessaries and the control group underwent amniotomy plus oxytocin infusion. These patients were alternately assigned either method of induction. They were further divided into primiparous and multiparous (parity 1 and 2 only) groups. Only 101 primiparas and 99 multiparas were available in the final analysis of the trial. Various aspects of labour, delivery, maternal and fetal outcome were compared. For primiparas, the traditional combined induction was the preferred method. For multiparas, both induction methods were quite satisfactory and there was a trend toward lesser blood loss and pethidine requirement in the PGE2 users.

Adolescent↗

Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia.

Immunohistological analysis of the expression of lactase protein in adults with hypolactasia has been carried out using monoclonal antibodies. Eight different antibodies that recognize at least three distinct epitopes on the lactase protein each gave the same result. Strong brush border staining was observed in all the lactase-persistent adults. No staining at all was detected in 9 of the hypolactasic subjects. In the remaining 12 individuals a mosaic pattern of expression was observed: small patches of enterocytes stained strongly, whereas the surrounding areas showed no staining at all. Sucrase-isomaltase, in contrast, showed no such mosaicism in these or in any of the other individuals. The mosaicism observed in the 12 hypolactasic individuals suggests that the differentiation of the columnar cells along the villus is not homogeneous. Furthermore, the existence of two patterns of expression of the lactase protein in the lactase-deficient individuals (i.e., absence of protein and mosaicism), if characteristic of the entire length of the intestine of the individuals tested, would suggest the existence of two phenotypes of adult-type hypolactasia in the population studied.

Antibodies, Monoclonal↗

An exercise in rational taxonomy.

The quest for a rational taxonomy of living forms began in the 17th century. Since the general acceptance of Darwin's theory of descent with modification, however, students of morphology became preoccupied with a systematics based on the genealogy of groups; and the rise of molecular phylogenies in recent years results in a further decline in the science of morphology. Reconstructing phylogenies by itself brings us no closer to the goal of rational taxonomy, which is to uncover the natural order inherent in the forms of living things. It is proposed that the rational taxonomy of forms should be derived from a study of development, much as von Baer had envisaged. To illustrate the method, a set of segmentation abnormalities in Drosophila larvae (previously exposed to either vapour) is considered, which can be individually classified as distinct disturbances in the process responsible for establishing normal segmental pattern. The process consists of a hierarchy of four successive bifurcations dividing the embryo's body first into two parts, then four, eight, and finally 16 subdivisions or segments. This gives rise to a taxonomic map of all possible transformations which contains the "phylogeny" of the actual forms and provides a natural system for classifying them. Attempts to recover the "true" phylogeny by various numerical methods are summarized and their implications for the validity of the basic assumptions of contemporary systematics discussed.

Animals↗

Isolation of a cDNA probe for a human jejunal brush-border hydrolase, sucrase-isomaltase, and assignment of the gene locus to chromosome 3.

We report the nucleotide sequence and derived amino acid sequence of a cDNA clone encoding most of the N-terminal, isomaltase region of human sucrase-isomaltase (SI). A plasmid containing this cDNA, pS12, identifies a 6-kb mRNA found in human jejunum and the human colon carcinoma cell line Caco-2. This human SI cDNA shows extensive overall homology with recently published rabbit SI cDNA. Using pS12 to probe DNA from a panel of somatic cell hybrids, we have assigned the gene encoding human SI to chromosome 3.

Amino Acid Sequence↗

A new paradigm for evolution.

Standard evolutionary theory sees little beyond the natural selection of random variation. Yet there is more to life.

Animals↗

Human lactase and the molecular basis of lactase persistence.

Human lactase purified from detergent extracts of the total membrane fraction of postmortem jejunum by means of monoclonal immunoadsorbent chromatography appears to be a dimer of subunits identical in Mr (160K). Trypsin or papain removes a small hydrophobic anchoring peptide from each subunit to give a hydrophilic enzyme which no longer interacts with detergent micelles. Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates, 4-methylumbelliferyl-beta-galactoside and beta-glucoside, as well as phlorizin; but it does not hydrolyze glucocerebroside. Phlorizin hydrolase is associated with lactase under all conditions investigated; coincident staining on immunodiffusion and immunoelectrophoresis, coincident elution on immunoadsorbent chromatography and on gel filtration in a dissociating buffer, and correlated reduction in activity in lactase-nonpersistent individuals. Adult and infant lactases are indistinguishable by titration or immunodiffusion against polyclonal rabbit antibodies. Adult individuals low in lactase activity also show a corresponding reduction in cross-reacting material. These observations suggest that lactase persistence is due to the continued synthesis of the infant enzyme.

Antibodies, Monoclonal↗

Bithorax phenocopy and pattern formation. II. A model of prepattern formation.

Phenocopy maps are constructed from the spatial pattern of the phenocopy spots using a distance function defined on the frequencies with which two compartments transform separately and jointly. The temporal changes in distances between different compartments in turn enable us to make inferences concerning the diffusion-like processes involved in prepattern formation of the metathorax. A model is presented which accounts for the data in terms of the propagation of two wavefronts in sequence and in approximately orthogonal directions. Sensitivity to transformation by ether is limited in time to the interval between the passing of the two wavefronts. Changes caused by 13 successive generations of ether treatment can be interpreted in terms of alterations in the timing and rates of wave propagation. A comparison of phenocopy and fate maps suggests that the prepatterning processes affect primarily the blastoderm cytoplasm or surface membrane.

Animals↗

Bithorax phenocopy and pattern formation. I. Spatiotemporal characteristics of the phenocopy response.

In four different lines of Drosophila melanogaster the highest frequencies of bithorax phenocopies result from ether treatment during the precellular blastoderm stages. The spatial characteristics of the phenocopy spots are dependent on the precise timing of phenocopy induction, and are not in accord with those predicted from the model of sequential determination of whole compartments put forward by Garcia-Bellido et al. in 1976. Ether treatment for 13 successive previous generations gave rise to changes in the spatiotemporal characteristics of the phenocopy response. Our results suggest the involvement of continuous diffusion-like processes in the prepatterning event which is affected by ether.

Age Factors↗

Lactase polymorphism in adult British natives: estimating allele frequencies by enzyme assays in autopsy samples.

In an attempt to estimate allele frequencies of lactase persistence in adult British natives, sucrase was assayed simultaneously with lactase under conditions that gave optimal activities for both enzymes. A trimodal distribution in the ratios of enzyme activities was demonstrated. Circumstantial evidence and statistical analyses suggest that the trimodal distribution is due to the different levels of lactase activity in the three genotypes--homozygous persistent, heterozygous, and homozygous nonpersistent, and that it is possible to correct for "nongenetic" variation by using sucrase as an internal standard. The allele frequency for lactase persistence was estimated to be .747. The implications of our findings on the genetic mechanisms involved in lactase persistence are discussed.

Adult↗