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Biomedical subjects

K Y Wong

Publications and source records attributed to K Y Wong.

At least 19 recordsLinked to original sources
PubMed1992

Growth factor receptor regulation in the Minn-1 leprechaun: defects in both insulin receptor and epidermal growth factor receptor gene expression.

Leprechaunism is a disorder characterized by intrauterine growth retardation, distinctive dysmorphology, and extreme insulin resistance due to structural abnormalities of the insulin receptor (IR). In addition to the IR, it has been suggested that abnormalities of the other growth factor receptors may occur in this syndrome. Using fibroblasts from the Minn-1 leprechaun, we have now investigated the expression of three different growth factor receptor genes: the IR, the insulin-like growth factor-I receptor (IGF-IR), and the epidermal growth factor receptor (EGFR). In agreement with previous studies, we found decreased insulin binding to fibroblasts from the Minn-1 leprechaun. In these cells, the IR transcription rate was not decreased, and sequence analysis of the IR promoter region of the patient showed no abnormalities. Both single-stranded conformational polymorphism analysis (SSCP) and DNA sequencing confirmed a previously reported nonsense mutation in one of the patient's two IR alleles at exon 14. mRNA levels for the IR were markedly decreased, suggesting that IR mRNA turnover was enhanced. We then studied the expression of the closely related IGF-IR Ligand binding, mRNA content, and transcription rate were all normal. In contrast to the IGF-IR, when the EGFR was studied, ligand binding and mRNA content were markedly decreased. These studies therefore raise the possibility that the phenotypic expression of leprechaunism results from defects in the expression of both the IR and the EGFR.

Abnormalities, Multiple↗
PubMed1992

Non-surgical closure of patent ductus arteriosus with the Rashkind PDA occluder system.

Transcatheter closure of Patent Ductus Arteriosus (PDA) was done in 18 children using the USCI Rashkind PDA occluder system. Patient age ranged from 1.2 to 14 years and their weights ranged from 8 to 36 kg. Isolated restrictive PDA was present in 15 patients; 3 had additional cardiac defects. The diameter of the PDA ranged from 2 to 6 mm as determined by lateral aortogram. PDA occlusion was successfully done in all 18 children. Ten 12 mm and eight 17 mm occluders were implanted with no complications. Post-implant aortogram showed complete ductal closure in 6 and trivial or small residual ductal flow in 12 cases. Doppler color flow mapping done within 3 days of the procedure showed complete ductal closure in 9, 8 had trivial ductal flow and 1 had small ductal flow. Transcatheter technique using a Rashkind PDA occluder system is a safe and effective method of non-surgical PDA occlusion.

Adolescent↗
PubMed1991

Production of inhibitor of insulin-receptor tyrosine kinase in fibroblasts from patient with insulin resistance and NIDDM.

Although non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in insulin action, the molecular basis of this resistance is unknown. We studied fibroblasts from a markedly insulin-resistant patient with NIDDM but without acanthosis nigricans. Her fibroblasts were resistant to insulin when alpha-aminoisobutyric acid uptake was measured. Fibroblasts from this patient demonstrated normal insulin-receptor content as measured by both insulin-receptor radioimmunoassay and by Scatchard analysis. However, when compared with nondiabetic control subjects, insulin-receptor kinase assays of wheat-germ-purified receptors prepared from her fibroblasts showed very low basal and no insulin-stimulated tyrosine kinase activity. The insulin receptor was then removed from the wheat-germ fraction by monoclonal antibody affinity chromatography. This insulin-receptor-deficient fraction inhibited both basal and insulin-stimulated tyrosine kinase activity of highly purified insulin receptors. When the specificity of this inhibition was tested, less inhibition was seen with insulinlike growth factor I-receptor tyrosine kinase, and even less inhibition was seen with the proto-oncogene p60c-src tyrosine kinase. Thus, these studies indicate that fibroblasts from an insulin-resistant patient with NIDDM produce a relatively specific glycoprotein inhibitor of insulin-receptor tyrosine kinase. Therefore, these studies raise the possibility that this inhibitor may play an important role in the insulin resistance seen in this patient.

Adult↗
PubMed1990

Insulin down-regulates insulin receptor number and up-regulates insulin receptor affinity in cells expressing a tyrosine kinase-defective insulin receptor.

We examined the effect of insulin treatment on HTC cells transfected with large numbers of either normal insulin receptors (HTC-IR) or insulin receptors defective in tyrosine kinase (HTC-IR/M-1030). In both HTC-IR and HTC-IR/M-1030 cells, 20 h of insulin treatment (1 microM) at 37 degrees C resulted in a 65% decrease in the number of binding sites with a reciprocal 6-fold increase in affinity. In contrast, treatment with 10 nM insulin (20 h, 37 degrees C) also increased receptor affinity but had a smaller effect on the number of binding sites. 125I-Insulin binding to soluble receptors from HTC-IR and HTC-IR/M-1030 cells pretreated with insulin showed results similar to those obtained in intact cells. In both HTC-IR and HTC-IR/M-1030 cells, insulin enhanced insulin receptor degradation. In HTC-IR/M-1030 cells a 1-h incubation with insulin did not change receptor number and had only a small effect on receptor affinity; also there was no effect of insulin after a 20-h incubation at 15 degrees C. Inhibiting protein synthesis by pretreatment with cycloheximide (100 microM) did not block either the decrease in receptor number or the increase in receptor affinity. Both HTC-IR and HTC-IR/M-1030 cells exhibited a very slow rate of insulin and insulin receptor internalization and no differences were seen in this parameter when HTC-IR cells were compared to HTC-IR/M-1030 cells. These studies indicate, therefore, that in cells expressing kinase-defective insulin receptors, insulin down-regulates insulin receptor number via enhanced receptor degradation, and up-regulates receptor affinity. These effects were time- and temperature-dependent, but not dependent on new protein synthesis, and suggest that activation of tyrosine kinase may not be a prerequisite for certain mechanisms whereby insulin regulates its receptor.

Animals↗
PubMed1990

Percutaneous balloon pulmonary valvuloplasty--the Singapore General Hospital experience.

Percutaneous balloon pulmonary valvuloplasty was performed in ten children aged 4 months to 9 years (mean age = 3.9 years). Their weights ranged from 5.6 to 38 kg (mean = 16.1 kg). Seven had typical pulmonary valve stenosis, two had pulmonary atresia and previous surgical valvotomy and one had dysplastic pulmonary valve. In patients with typical pulmonary valve stenosis, significant reductions in the right ventricular systolic pressure and pulmonary systolic pressure gradients were observed immediately after balloon dilatation. Follow-up evaluation by Doppler echocardiography at six months to two years showed further reduction in pulmonary gradients in five, and in the other two, the gradients remained low. Reduction in right ventricular pressure was less in patients with pulmonary atresia and previous surgical valvotomy and patients with dysplastic pulmonary valve. Balloon pulmonary valvuloplasty is a safe and effective procedure for the relief of typical pulmonary valve stenosis. In patients with pulmonary atresia and previous surgical valvotomy, balloon valvuloplasty can be an effective palliation for decompressing the right ventricle and improving pulmonary blood flow.

Blood Flow Velocity↗
PubMed1990

Balloon atrial septostomy under two dimensional echocardiographic visualisation.

From May 1988 to January 1989, we performed balloon atrial septostomy under Two Dimensional Echocardiographic visualisation on 8 patients at the bedside in the intensive care unit, in the Singapore General Hospital. Their ages ranged from 3 to 45 days (median = 7 days). Their weights ranged from 1.6 to 4.0 kg (mean +/- 2sd = 3.2 + 1.6). Five patients had transposition of the great arteries, 1 had tricuspid atresia and 2 with pulmonary atresia/stenosis. There were no complications related to the procedure. The advantage of Two Dimensional Echocardiographic imaging compared to fluoroscopy are 1) excellent visualisation of cardiac structures, 2) it can be performed safely at the bedside without transporting patient to the cardiac catheter laboratory, 3) Immediate detection of cardiac complications and 4) no radiation exposure. Balloon atrial septostomy done using Two Dimensional Echocardiographic visualisation is acceptable and safe. It is the method of choice in our department.

Cardiac Catheterization↗
PubMed1979

Evaluation of 24-hour infusion of high-dose methotrexate--pharmacokinetics and toxicity.

High-dose methotrexate was administered by constant infusion over 24 h to children with various malignancies. Citrovorum factor was given at the completion of methotrexate infusion and continued for 72 h. Serum concentration of 10(-4) M could be sustained for 24 h with doses of methotrexate over 100 mg/kg. This infusion regimen was well tolerated and only mild neutropenia and mouth sores were seen in most patients. Severe toxicity was seen in one patient and was related to prolonged retention of methotrexate in the circulation. Careful monitoring of serum drug level is mandatory in the use of any high-dose methotrexate regimen.

Adolescent↗
PubMed1978

Entry of insulin into human cultured lymphocytes: electron microscope autoradiographic analysis.

Electron microscope autoradiographs were prepared of IM-9 human cultured lymphocytes incubated with iodine-125-labeled insulin. With the use of [125I]insulin and Ilford L-4 emulsion, the technique had a resolution half-distance of approximately 0.085 micrometer. Autoradiographs revealed a time-dependent entry of insulin into the cell interior that was maximal after 30 minutes of incubation. At this time point nearly 40 percent of the [125I]insulin was in the interior of the cell at a distance 1 micrometer or greater from the plasma membrane. Grain distribution and volume density analyses revealed that the intracellular insulin was concentrated in the endoplasmic reticulum and nuclear membrane.

Autoradiography↗
PubMed1978

Severe infiltration of the kidneys with ultrasonic abnormalities in acute lymphoblastic leukemia.

A 3-year-old boy with acute lymphoblastic leukemia had enlarged kidneys with impairment of renal function and hypertension as the presenting features of relapse. Ultrasound demonstrated multiple nodular areas of echolucency within enlarged kidneys that reverted to normal when the patient was in remission but then recurred during relapse. This noninvasive procedure may be useful in patients with acute lymphoblastic leukemia to determine the incidence and prognostic significance of renal involvement at the time of diagnosis, and to follow the course of those who have demonstrable changes.

Child, Preschool↗
PubMed1978

Leukemic infiltration of the testis during long-term remission.

Of 33 boys with acute lymphocytic leukemia treated at the Cincinnati Children's Hospital during 1971--1974, 14 remained in clinical and bone marrow remission for periods longer than 2.5 yr. Of these 14 patients, 8 then developed testicular leukemia. In 7 of these 8 patients, testicular infiltration was the first or only evidence of relapse. In 2 of the patients the gonads were not grossly abnormal, and testicular relapse was discovered as a result of routine wedge biopsy before therapy was to have been stopped. This experience has led to our policy of routine testicular biopsy in boys with acute lymphocytic leukemia who have had continuous remission for 3 yr and who are otherwise candidates for discontinuance of maintenance therapy.

Adolescent↗
PubMed1977

Acute respiratory illness in children with acute lymphoblastic leukemia.

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.

Central Nervous System Diseases↗
PubMed1977

Cellular uptake and nuclear binding of insulin in human cultured lymphocytes: evidence for potential intracellular sites of insulin action.

Human cultured lymphocytes (IM-9) were used to demonstrate that insulin can enter the intact cell and bind to the nucleus. When these lymphocytes were incubated with 125I-labeled insulin, specific cellular uptake reached a maximum within 2 min and remained at a plateau for 90 min or longer. Partially purified nuclei from such cells contained approximately 15-20% of the total cellular radioactivity. Nuclei freed of all other cellular fractions (by washing the partially purified nucleic with Triton X-100) bound approximately 7% of the total cellular radioactivity. In contrast to the rapid uptake of labeled insulin into the intact cell, specific binding to the nucleus was half-maximal after 5 min of incubation and maximal after 90 min. Both the cellular uptake and subsequent nuclear binding of labeled insulin were progressively inhibited by increasing concentrations of unlabeled hormone. Independent evidence for the nuclear binding of insulin was obtained by preparing autoradiographs of lymphocytes incubated for various times with labeled insulin. Such preparations strongly suggest that insulin binds to the plasma membrane, enters the cytosol, and then binds to the nucleus.

Biological Transport↗
PubMed1976

Surface markers and prognostic factors in acute lymphoblastic leukemia.

We investigated the surface markers on lymphoblasts from 37 patients with acute lymphoblastic leukemia. Spontaneous rosette formation with sheep erythrocytes (E rosettes) identified T cells and the presence of surface immunoglobulin identified B cells. Eight patients had T-marker lymphoblasts; 28 had no markers (null lymphoblasts), and one patient had B-marker lymphoblasts. The eight patients with T-marker acute lymphoblastic leukemia had massive leukemic infiltration, frequently a mediastinal mass, and a poor prognosis. The T-marker lymphoblasts had a weak or negative periodic acid-Schiff reaction and a very low antigenic stimulation to allogeneic lymphocytes. The association of T-marker lymphoblasts and some of the conventional poor-risk factors appears to be reliable in predicting a poor prognosis.

B-Lymphocytes↗
PubMed1976

Rhmod, a second kindred (Craig).

Three Rhmod siblings were found to have identical Rh: w1, w2, -3, -4, w5 (see article) phenotypes. All had stomatocytic hemolytic anemia. On quantitative hemagglutination studies, as well as on hand tests, all Rh antigens were not equally depressed. Rh17 (Hr0, 'not D') and Rh29 (RH, 'total Rh') were both normal. Rh5 (hr", e) was only slightly depressed. Rh25 (LW) had 50% of the expression expected in normal Rh:-1 cells. Rh1 (Rh0, D), Rh13 (RhA), Rh14 (RhB), Rh15 (RhC), and Rh16 (RhD), were severely depressed. Rh2 (rh', C) was depressed, while Rh7 (rhi, Ce) was absent. Both Rh19 (hrS) and Rh31 (hrB) were depressed. Rh12 (rhG, G) was distinctly depressed, scoring considerably less than rGrG red cells. The unrelated parents, the child of the proposita, and some siblings of each parent showed lessened depression of Rh antigens without displaying the consistent pattern that might be expected from a presumed single suppressor gene. Absence of a consistent pattern may have resulted from differing Rh genotypes, but a frequently observed depression involved Rh14, Rh15, and Rh16 (RhB, RhC, and RhD) without an effect on either Rh1 (RH3 or D) or Rh13 (RhA).

Female↗