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Biomedical subjects

H H Chiu

Publications and source records attributed to H H Chiu.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mucosal addressin cell adhesion molecule-1: a structural and functional analysis demarcates the integrin binding motif.

The leukocyte integrin receptor, alpha 4 beta 7, and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) are postulated to be important in regulating lymphocyte trafficking to normal intestine. Here we provide the first description of MAdCAM-1 expression in inflamed intestine. Using mouse models of experimentally induced colitis, we show a concordant increase in MAdCAM-1 expression associated with increased cellular infiltrates in areas of intestinal inflammation. To understand more of the molecular nature of the interactions between MAdCAM-1 and its leukocyte ligand, the alpha 4 beta 7 integrin receptor, we have analyzed the structural and functional properties of chimeric recombinant MAdCAM-1 proteins in vitro. Using site-directed mutagenesis and molecular modeling, we demarcate the alpha 4 beta 7 binding motif as three linear residues within the C-D loop in the first domain of MAdCAM-1. Mutation of residue L40, D41, or T42 in the first domain completely abrogates alpha 4 beta 7+ cell binding and cellular activation. Mutagenesis of other residues in the first domain do not impact these functions. We have modeled peptides based on the predicted structure of the alpha 4 beta 7 integrin binding motif on MAdCAM-1 and are able to show specific and selective blocking of cell binding. These observations suggest that the amino acid residues LDT on MAdCAM-1 play a role in the interaction with alpha 4 beta 7 in cell adherence and cell activation.

Amino Acid Sequence↗
PubMed1996

Homocystinuria presenting as fatal common carotid artery occlusion.

A patient with homocystinuria presenting with fatal cerebral infarction that resulted from left common carotid artery occlusion is reported. This 13-year-old, healthy and intelligent girl presented with progressive cerebral infarction. Angiography revealed total occlusion of the left common carotid artery and stenosis of the right common carotid artery. Distal stenosis of bilateral vertebral arteries was also observed. Initially Takayasu arteritis with unusual manifestation was considered. However, later investigations revealed homocystinuria was the underlying cause. The sudden onset of fatal stroke as the initial clinical presentation of homocystinuria, as observed in this previous healthy teenager, is noteworthy. We suggest metabolic screening for homocystinuria when treating a patient with unusual vascular lesions.

Adolescent↗
PubMed1996

Case report: paucity of interlobular bile ducts in Chinese children.

Sixteen Chinese children with cholestasis since early infancy were diagnosed to have paucity of interlobular bile ducts (PILBD) or its equivalent. Twelve children belonged to the syndromic group of PILBD and four children belonged to the non-syndromic group. A definite histological diagnosis of bile duct paucity was established in only two children (aged 4 and 9 months) during the first percutaneous needle biopsy. In the remaining 14 children a varying degree of bile duct destruction was evident in the follow up percutaneous or wedge liver biopsies. The evolving changes were characterized by inflammatory infiltration near or at the ductal wall, the presence of dysmorphic ductules, the degeneration of ductal epithelia and a progressive decrease of interlobular bile ducts. Of 10 children who underwent laparotomy for definite diagnosis, kasai operation was performed in two of them. In the syndromic PILBD group, all children, including two paired siblings, had at least three of five major clinical features. Hypoplasia of the extrahepatic biliary tree was found in five children and atresia of the extrahepatic bile duct was found in one. Three of six children studied were shown, by polymerase chain reaction, to have cytomegalovirus infection in the liver. This study demonstrates that bile duct paucity is a result of progressive bile duct destruction. A definitive diagnosis is difficult to make in early infancy. Thus, the careful evaluation of extrahepatic features in cholestatic children and follow-up liver biopsies are indicated. Although the pathogenetic mechanism of PILBD is unknown, bile duct destruction is the common pathway leading to paucity of bile ducts irrespective of syndromic or non-syndromic types.

Bile Ducts↗
PubMed1996

Influenza B virus infection associated with shock in a two-month-old infant.

Influenza B virus usually causes a mild and self-limiting illness. A 2-month-old infant presented with acute symptoms suggestive of septic shock but recovered after vigorous resuscitation 1 day later. Influenza B was isolated from a throat swab taken from the infant. Bacterial cultures of blood, urine and spinal fluid had no growth. This case illustrates that the clinical signs and symptoms of influenza in infants may be indistinguishable from bacterial sepsis.

Humans↗
PubMed1995

Similar but nonidentical amino acid residues on vascular cell adhesion molecule-1 are involved in the interaction with alpha 4 beta 1 and alpha 4 beta 7 under different activity states.

The integrin receptors alpha 4 beta 1 and alpha 4 beta 7 both bind to vascular cell adhesion molecule-1 (VCAM-1). Here, we report that the amino acid residue requirements for murine VCAM-1 adhesion to murine alpha 4 beta 1 (WEHI 231) and alpha 4 beta 7 (38C13/beta 7-transfectant) positive cells are strikingly similar but nonidentical under multiple adhesion activity states. By site-directed mutagenesis of domain 1 of VCAM-1, the amino acid residues on the loop between beta strands C and D (R36, Q38, I39, D40, P42) and on the adjacent antiparallel beta strand F (L70 and T72) were required for basal level adhesion to both alpha 4 beta 1-positive and alpha 4 beta 7-positive cells. Mutation at two other sites, N44 (loop between beta strands C and D) and E66 (loop between beta strands E and F), specifically reduced alpha 4 beta 7-positive cell adhesion, but not alpha 4 beta 1-positive cell adhesion. Mutation H85A augmented alpha 4 beta 7 binding but not alpha 4 beta 1 binding. These apparent differences relate to the higher intrinsic activity state of alpha 4 beta 1 on WEHI 231 than on alpha 4 beta 7 (38C13/beta 7-transfectant). In contrast, under higher adhesion activity states induced by either MnCl2 or truncation of the beta 7 cytoplasmic tail, mutation of either amino acid residue D40 or L70 completely blocked cell adhesion without evidence of structural perturbation of VCAM-1. These results suggested that the two structurally discontinuous amino acid residues, the negatively charged D40 and the hydrophobic L70 adjacently located on domain 1 of VCAM-1, are essential for interaction under multiple activity states with both alpha 4 beta 1 and alpha 4 beta 7 integrin receptors.

Amino Acid Sequence↗
PubMed1995

The association of syndromic paucity of the interlobular bile ducts and congenital mechanical obstruction of the small intestine.

Three patients with congenital mechanical intestinal obstruction and features of syndromic paucity of the interlobular bile ducts (SPILBD) are presented. Two of them have siblings with syndromic paucity of the interlobular bile ducts. Two patients had jejunoileal atresia, while the other had a meconium plug with intestinal perforation. All subjects underwent surgery for intestinal obstruction within the first 24 h of life. Progressive disappearance of the bile ductules was observed in one case. We believe that an insult such as vascular insufficiency to both bile ductal epithelium and the small intestine may be the cause of this congenital disorder.

Abnormalities, Multiple↗
PubMed1995

Recombinant alpha-interferon treatment of intracranial hemangioma and Kasabach-Merritt syndrome in an infant with cytomegalovirus.

A 2-month-old girl presented with enlarged head girth, generalized petechiae, anemia, coagulopathy and hepatosplenomegaly. Imaging studies showed a huge, dumbbell-shaped intracranial hemangioma located between the falx, and involving the supra- and infra-tentorium, extending through the posterior fontanel to involve the subgaleal area. A urine culture grew cytomegalovirus. Severe thrombocytopenia was refractory to a massive platelet transfusion, intravenous immunoglobulin and corticosteroid therapy. Hypertension, pulmonary hemorrhage and sepsis complicated the course. After establishing a diagnosis of Kasabach-Merritt syndrome, subcutaneous injections of alpha-interferon were given with an initial dose of 1 x 10(6) IU/m2 followed by 3 x 10(6) IU/m2 per day for 12.5 mo. Her platelet count rose gradually and became stable after 1.5 mo of interferon treatment. The intracranial hemangioma regressed remarkably and the hepatosplenomegaly was also resolved. The infant showed good growth and development, without obvious side-effects during the 23-month follow-up period. The treatment with recombinant alpha-interferon appeared to be effective in reversing thrombocytopenia associated with the patient's massive intracranial hemangioma.

Brain Neoplasms↗
PubMed1994

Structural requirements for adhesion of soluble recombinant murine vascular cell adhesion molecule-1 to alpha 4 beta 1.

This study describes the identification of seven amino acid residues of the vascular cell adhesion molecule (VCAM-1) that influence binding to the alpha 4 beta 1 receptor. Using recombinant murine VCAM-1-IgG, which is bound by both mouse (WEHI 231) and human (Ramos) lymphoid cells, two approaches demonstrated the crucial role of the first two NH2-terminal Ig-like domains in binding: (a) blocking monoclonal anti-mouse VCAM-1 antibodies bound to only truncation variants that included the first two domains; (b) site-direct mutagenesis of the first NH2-terminal domain showed that alanine substitution of the amino acid residues R36, D40, K46, S54, N65, T72, and E81 partially or completely reduced adherence by human and/or mouse cells. Of these D40, when mutated to A, N, or K (but not E), showed complete abrogation of adherence by mouse and human cells, as well as inability to bind blocking anti-murine VCAM-1 antibody MVCAM.A429, while not inducing gross structural perturbations in VCAM-1. By molecular modeling, the D40 residue was located on a beta turn connecting two beta strands defined as C and D. The residues R36, K46, S54, N65, T72, and E81, which perturb cell adherence and caused small changes to gross structure, are conformationally near or adjacent to D40. Although these residues, identified as crucial for cell adhesion, are all located in domain 1, it is evident that there is a structural requirement for domains 1 and 2 to be intact so that cell adhesive function can occur.

Amino Acid Sequence↗
PubMed1989

In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice or mice with minimal levels of anti-C. albicans sensitivity, females somewhat more so than males, were sensitive to suppressive effects of in vivo treatment with rMuIFN-gamma when challenged with C. albicans. In contrast, under conditions similar to those of humans, in whom underlying immunity to C. albicans is usually present, suppression of host responses to C. albicans was not observed in immunized mice in response to treatment with rMuIFN-gamma.

Animals↗
PubMed1989

Interferon-gamma increases alveolar macrophage Ia antigen expression despite oral administration of dexamethasone to rats.

Corticosteroids have multiple effects on immune and inflammatory responses and decrease host resistance to a broad range of microorganisms. Resident tissue macrophages have been proposed as a target for the immunosuppressive effects of corticosteroids and are important in host defense against infections. During infection-induced immune responses, macrophages are activated after exposure to interferon-gamma (IFN-gamma), and class II major histocompatibility (Ia) antigens on their surface are increased. We investigated the effect of orally administered corticosteroids on alveolar macrophages, the resident macrophages of the lung parenchyma. We hypothesized that corticosteroids would inhibit the activation of alveolar macrophages and measured induction by IFN-gamma of Ia antigens as a marker of cell activation. Alveolar macrophages from normal and corticosteroid-treated rats were exposed to recombinant murine IFN-gamma (rMuIFN-gamma) in vitro and assayed for Ia transcription and surface Ia expression. Ia mRNA accumulation was induced in alveolar macrophages from normal and corticosteroid-treated rats after exposure in vitro to rMuIFN-gamma. Furthermore, rMuIFN-gamma increased surface expression of Ia proteins on alveolar macrophages from corticosteroid-treated rats, although to a lesser extent than on cells from control rats. Finally, surface Ia expression could also be increased in vivo by exposure of corticosteroid-treated rats to an aerosol containing rMuIFN-gamma. These results demonstrate that administration of oral corticosteroids, while establishing a state of immunosuppression in rats, does not abolish responsiveness of rat alveolar macrophages to rMuIFN-gamma. We speculate that IFN-gamma-induced augmentation of phagocytic cell function may constitute an important therapeutic modality to treat complications of immunodeficiency.

Administration, Oral↗
PubMed1988

Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells.

We have examined the effects of transforming growth factor-beta (TGF-beta 1) on the expression of the class II histocompatibility Ag, HLA-DR: 1) induced by human rIFN-gamma (rHuIFN-gamma) in human melanoma, Hs294T cells and 2) constitutively expressed in a subclone Hs294T cell line. The expression of HLA-DR Ag on Hs294T cells was induced by rHuIFN-gamma in a dose- and time-dependent manner with maximal levels obtained with 10 ng/ml rHuIFN-gamma after 48 h exposure. Treatment of Hs294T cells with natural porcine platelet-derived or human rTGF-beta 1 (1 to 100 ng/ml) in the presence of rHuIFN-gamma (0.1 to 10 ng/ml) reduced the percentage of cells positive for this Ag by approximately 40 to 50%, as determined by flow cytometry. This suppressive effect of TGF-beta 1 was not restricted to Hs294T cells inasmuch as rHuIFN-gamma induced HLA-DR surface Ag expression on PBMC-derived adherent cells was also significantly inhibited by TGF-beta 1. Northern blot analysis of cytoplasmic RNA extracted from Hs294T cells indicated that the decreased levels of HLA-DR cell-surface Ag correlated with decreased levels of mRNA transcripts encoding this Ag. TGF-beta 1 also effectively reduced the levels of HLA-DR mRNA in 1) cells that had been pretreated with rHuIFN-gamma and were expressing maximal levels of HLA-DR surface antigen and 2) cells that constitutively expressed HLA-DR surface Ag without exogenous rHuIFN-gamma treatment.

Antigens, Surface↗
PubMed1980

Irreversible thermodynamics of an isometric twitch, time-dependent general formulation.

We used the phenomenological laws of irreversible thermodynamics, to derive a system of coupled differential equations describing the time course of the mechanochemical coupling underlying an isometric twitch. Our general description is concerned only with the fundamental process of energy transduction taking place within an idealized unit element of muscle and does not include the description of associated processes such as the excitation-contraction coupling and the mechanical or external coupling that, in bulk muscle, lead to or mediate the fundamental process. The values of the initial conditions and of four parameters are required to solve for the time course of the process. Two of the parameters have a clear physical interpretation and, for the specific case of muscular contraction involving hydrolysis of ATP, their values can be readily estimated from available experimental data. The interpretation of the two other parameters is more speculative, but, from their strong interdependence with the other parameters, their values can be also approximated. Solution of the coupled differential equations yields results consistent with the typical experimental time course of an isometric twitch.

Mathematics↗
PubMed1978

Clinical evaluation of etomidate as an induction agent.

A comparative study between Etomidate and Thiopentone was carried out on 100 healthy female patients scheduled for post-partum abdominal sterilization under epidural analgesia. Our results show Etomidate to be a safe and effective induction agent, comparable to Thiopentone in having a rapid onset of action and rapid recovery time. The pulse rates and blood pressures remained relatively stable during the use of Etomidate. However, there was a high incidence of transient respiratory upsets while causing less respiratory depression than Thiopentone. The objectionable features of Etomidate are high incidence of pain on injection and involuntary muscular activity, which account for the low anaesthetist acceptance rate.

Adult↗
PubMed1978

Acid aspiration during laparoscopy.

The prophylactic efficacy of pre-operative antacid administration was shown by comparing the pH and volumes of gastric contents in 50 female patients treated with 10 ml of Mist. Magnesium Trisilicate B.P.C. with that of 50 controls. Routine antacid prophylaxis was advocated for all patients undergoing pelvic laparoscopy as intra-operative conditions increase the risk of pulmonary acid aspiration.

Adolescent↗
PubMed1978

Effects of etomidate given in repeated doses.

Fifty fit, female patients were given four consecutive intravenous doses of etomidate 10 mg, so as to maintain sleep, after establishment of epidural block for postpartum sterilization. A matched group was given four doses of thiopentone 125 mg. Cumulative hypnotic effect, as judged by increasing sleep duration with second and subsequent doses, was much less with etomidate than with thiopentone. Etomidate did not depress blood pressure, whereas it fell progressively with successive doses of thiopentone. Injection pain was reported in 68% of patients receiving etomidate, and this tended to increase with successive doses; 12% also showed local inflammation at the injection site. Tremor, due to etomidate, was common, but did not increase with successive doses. Feelings of sleepiness, lasting several hours after waking, were more common after thiopentone than after etomidate.

Anesthesia, Epidural↗
PubMed1977

Complication of laparoscopy under general anaesthesia.

Two cases are presented in which injury to the stomach occurred in association with laparoscopy under general anaesthesia. The common aetiological factor was gastric inflation resulting from I.P.P.V. via mask. Precautionary measures in the anaesthetic induction technique are described.

Adult↗