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Biomedical subjects

C Y Kuo

Publications and source records attributed to C Y Kuo.

At least 37 records · Page 2Linked to original sources

Stimulated human leukocytes cause activating mutations in the K-ras protooncogene.

Human tissues which are chronically infiltrated with inflammatory leukocytes are more likely to develop malignancies than non-inflamed tissues, however the mechanism(s) by which leukocytes contribute to carcinogenesis is unknown. Stimulated human leukocytes release superoxide anion and hydrogen peroxide which, in the presence of iron, can be converted into the potent oxidant, hydroxyl radical (.OH). Previous studies have shown that leukocyte-derived .OH (or a .OH-like species) can cause DNA damage, however a relationship between leukocyte-induced DNA damage and carcinogenesis has not been established. The present report demonstrates that leukocyte-derived .OH-induced DNA damage can cause K-ras oncogene activation, and suggests that there may be a characteristic pattern of .OH-induced K-ras oncogene activation. Since activation of the K-ras oncogene is believed to play a crucial role in the pathogenesis of many human malignancies, .OH-induced K-ras oncogene activation could be an important mechanism by which human leukocytes contribute to carcinogenesis.

3T3 Cells↗

Retinal function abnormalities in membranoproliferative glomerulonephritis type II.

PURPOSE: To characterize retinal electrophysiologic and psychophysical abnormalities associated with membranoproliferative glomerulonephritis type II. METHODS: Three adults with membranoproliferative glomerulonephritis type II were studied. Retinal function was measured psychophysically (automated perimetry, Farnsworth D-15 color vision testing, and dark adaptometry) and electrophysiologically (full-field flash electroretinography and electro-oculography). RESULTS: Two symptomatic individuals had prominent drusenlike deposits and retinal pigment epithelial disturbances, findings characteristic of membranoproliferative glomerulonephritis type II retinopathy. These individuals had mild visual field and color vision abnormalities, prolonged dark adaptation, and delayed electroretinographic dark-adapted dim and bright flash responses of normal amplitude. The electro-oculogram of the most severely affected individual was abnormal. The third individual who was asymptomatic had the mildest fundus abnormalities and exhibited normal psychophysical and electrophysiologic responses. CONCLUSIONS: Membranoproliferative glomerulonephritis type II retinopathy may be associated with symptomatic and measurable psychophysical and electrophysiologic abnormalities of retinal function.

Adult↗

A nationwide epidemiological study of spinal cord injury in geriatric patients in Taiwan.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out among patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. In all, 1,586 new cases of SCI were registered, representing about 70% of all possible SCI cases in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million people, whereas it was 47.5 for the geriatric section. The mean age was 46.1 years with a plateau distribution after 20 years and older. Geriatric victims (297 cases, 18.7%, group II) formed a major section of SCI cases in Taiwan. Another group of younger SCI patients (15-64 years old, 1,232 cases, group I) was selected for comparison. The results showed that the male-to-female ratio, pattern of neurological deficits, and causes of injury and death of geriatric SCI patients differed significantly from those of the younger SCI group. Elderly women were exposed to a higher risk of SCI than younger women (M/F ratio 1.7:1). Falls were the leading cause of geriatric SCI, and two thirds of them occurred on level ground. Traffic accidents accounted for a third of SCI cases, half of which involved motorcycle accidents, a fifth of them pedestrians. Quadriplegia and quadriparesis occurred more frequently among elderly cases of SCI than in the younger group and a higher proportion of them died of SCI complications. Two thirds of elderly SCI patients recovered well enough after comprehensive treatment to be able to take care of themselves at home. The government should initiate programs of prevention to reduce the prevalence of geriatric SCI in Taiwan.

Age Factors↗

Effect of leak around the endotracheal tube on measurements of pulmonary compliance and resistance during mechanical ventilation: a lung model study.

We studied the effect of leaks around the endotracheal tube (ETT) on the measurement of pulmonary mechanics during mechanical ventilation. We also evaluated the influence of different ventilator settings on the magnitude of leak. An adjustable leak was created at the end of the ETT in a lung model with constant compliance. Flow, tidal volume, and pressure changes were measured above and below the leak. Compliance (Ci) and resistance (Ri) during inspiration were determined by linear regression analysis (LRA) using the equation of motion and the Mead and Wittenberger method (MWM). The ventilatory change that influenced the degree of leak most was prolongation of inspiratory time (Ti). The presence of a leak around the ETT resulted in an overestimation of the Ci and Ri values, which was proportional to the size of the leak. This overestimation was also influenced by the method used to determine Ci and Ri. Because the contribution of the leak to the fidal volume progressively increases as inspiration continued, methods of analysis that depended mainly on measurement points at the end of inspiration showed a larger deviation from the true Ci and Ri values than methods mainly influenced by measurement points at the beginning of inspiration. Because of this, shortening of inspiration, or analysis of points at the beginning of inspiration reduces the error in the measurements of Ci and Ri when a leak is present. Breaths with a large leak should be excluded from any analysis of pulmonary mechanics.

Airway Resistance↗

Treatment of patent ductus arteriosus with low-dose indomethacin in very low birth weight neonates with impairment of renal function: report of three cases.

This paper reports three cases of very low-birth-weight preterm infants with impairment in renal function and occurring simultaneously with patent ductus arteriosus (PDA). The PDA was treated successfully with low-dose indomethacin without adverse effects. Only one patient had recurrence of the PDA, and the PDA was closed again in this case without problems using the same regimen. One of the other two cases died of necrotizing enterocolitis one month later. The hospital course of the remaining case was uneventful thereafter. It is suggested that low-dose indomethacin can be applied safely in a situation that is conventionally regarded to be a contraindication to the use of indomethacin such as impairment in renal function.

Adult↗

Neonatal endotracheal tube leakage and compliance and resistance measurements.

The effects of neonatal endotracheal tube (ETT) leakage on inspiratory compliance (Ci) and resistance (Ri) were examined using a lung model with constant compliance. An air leak was created at the end of an ETT. Flow was measured at, above and below the leak by a hot wire anemometer and a pneumotach. Tidal volume (VT) was derived from digitally integrated flow. Pressure was measured at the side port of the ETT adaptors above and below the leak. Percent of air leak (% leak) was defined as the difference between inspiratory volume above (VTa) and below (VTb) the leak divided by VTa and multiplied by 100. Ci and Ri were analyzed conventionally and by linear regression. Percent error of Ci was defined as the difference between inspiratory compliance above the leak (Cia) and below the leak (Cib) divided by Cia and multiplied by 100. The results showed that the inspiratory time (Ti) of the ventilatory setting is the most important factor for determining %leak. Percent error of Ci is in proportion to %leak. The change in inspiratory resistance is complicated, depending on the ventilatory setting, leak site resistance and the method of analysis. This study demonstrates the origin of the computational error in breaths with ETT leakage diagramatically and by use of mathematics. It suggests that air leakage may contribute to a high variability in compliance and resistance measurements.

Diagnosis, Computer-Assisted↗

Synaptic vesicle-associated glutamate decarboxylase: identification and relationship to insulin-dependent diabetes mellitus.

Glutamic acid decarboxylase (GAD) catalyzes the biosynthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). GAD has been suggested as an autoantigen in insulin-dependent diabetes mellitus and stiff-man syndrome. Recently, three forms of membrane-associated GAD (MGAD) have been characterized in porcine brain, but the subcellular localization and function of these proteins are unknown. We present evidence that GAD activity is associated with synaptic vesicles from porcine brain. These vesicles contain a 60 kDa protein recognized by serum from patients with insulin-dependent diabetes mellitus, probably MGADII, as shown by subcellular fractionation and immunoblotting. These results raise the possibility that the association of MGADII with synaptic vesicles may be crucial for its role as an autoantigen in insulin-dependent diabetes mellitus.

Animals↗

An integral membrane protein form of brain L-glutamate decarboxylase: purification, characterization and its relationship to insulin-dependent diabetes mellitus.

A new and novel form of L-glutamate decarboxylase (GAD; EC 4.1.1.15) was purified from whole porcine brain to apparent homogeneity by a combination of column chromatographies on DE-52, ultragel AcA 34, hydroxylapatite and Sephadex G-200, and native gel electrophoresis. The purified GAD was established as an integral membrane protein based on hydrophobic interaction chromatography and membrane extraction studies. This membrane GAD (MGAD) has a native molecular weight of 120 +/- 5 kDa and is a homodimer of 60 +/- 2 kDa. Immunoprecipitation and immunoblotting tests using the sera from insulin-dependent diabetes mellitus (IDDM) patients revealed the presence of antibodies against this newly identified MGAD in IDDM. The role of MGAD in the pathogenesis of IDDM and related autoimmune disorders is also discussed.

Diabetes Mellitus, Type 1↗

A membrane form of brain L-glutamate decarboxylase: identification, isolation, and its relation to insulin-dependent mellitus.

A membrane form of L-glutamate decarboxylase (GAD) was identified and purified to apparent homogeneity from hog brain. The purified GAD was established as an integral membrane protein by phase-partitioning assay, charge-shift electrophoresis, and chromatography on a hydrophobic interaction column. This membrane GAD has a native molecular mass of 96 +/- 5 kDa and is a homodimer of 48 +/- 3-kDa subunits. Immunoprecipitation and immunoblotting tests revealed the presence of antibodies against this membrane GAD in sera from patients with insulin-dependent diabetes mellitus. Since this form of GAD appears to be an integral membrane protein and is presumed to have extracellular domains exposed, it seems reasonable to suggest that membrane GAD is more likely than soluble GAD to be involved in the pathogenesis of insulin-dependent diabetes and related autoimmune disorders such as stiff-man syndrome.

Animals↗

Osteogenesis imperfecta in a family.

Osteogenesis imperfecta (OI) is a rare, inherited condition in which not only the bones are abnormally brittle but also abnormalities in the ligamentous structures, of the eye, ear and skin coexist. Three members of the same family experienced the pathologic fractures with squaring deformity, but no blue sclerae or deafness. They presented with a relatively benign course treated conservatively.

Adult↗

Magnetic resonance imaging of the kidneys in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a blood cell disorder characterized by repeated intravascular hemolysis. Histologically, there is hemosiderin deposition in the proximal tubular cells of the renal cortex. We report a case of PNH with characteristic magnetic resonance findings. The signal intensity of the renal cortex was markedly decreased in various pulse sequences because of the T2-shortening paramagnetic effect of hemosiderin. The significance of signal intensity ratios between renal cortex and medulla, renal cortex and skeletal muscle are discussed. These ratios of the PNH patient are significantly different from those of normal controls (p = 0.0000).

Adult↗

First alveolar-arterial oxygen gradient (AADO2) in mechanical ventilation as a predictor for duration of intubation in respiratory distress syndrome.

From January 1988 to May 1992, 33 premature infants (inborn, gestational age less than 35 weeks), put on respirator therapy (before six hours of age) due to severe respiratory distress syndrome (RDS), were studied to examine if the first alveolar-arterial oxygen gradient (AaDO2) after initiating mechanical ventilation could be used as a predictor of intubation duration. They were divided into three groups: nine cases without associated diseases or severe complications who were successfully extubated (group I), 10 cases with associated diseases or severe complications who were successfully extubated (group II), and 14 cases where death occurred before extubation (group III). After intubation, the relationship between the first AaDO2 and the intubation duration thereafter was examined. A significant correlation between AaDO2 and the number of days of intubation was demonstrated only in group I (r = 0.93, p < 0.001). Among the groups, the means of the gestational ages, Apgar scores, data of the first arterial blood gas sample and ventilator settings after intubation, and AaDO2 were not statistically different. The results suggest that the first AaDO2 cannot be used to predict mortality and morbidity, but it can be used as a predictor of the number of days of intubation in surviving RDS infants without associated diseases or severe complications. If a surviving patient with RDS is not extubated by the expected date, one should search for possible associated diseases or severe complications.

Blood Gas Analysis↗

Formation of pseudoislets from human pancreatic cultures.

We have successfully developed a technique for culturing human islet cells obtained from the cadaveric pancreata of children. Within 24-48 h of in vitro culture, collagenase-digested human pancreatic tissue formed epithelioid monolayers. Scattered within these monolayers were insulin-positive cells, as detected by immunocytochemical and dithizone staining. Treatment of the beta cell-containing epithelioid-cell monolayers with EDTA resulted in the formation of spherical cellular clusters, i.e., pseudoislets. These pseudoislets differed from isolated islets of Langerhans in that they showed a more peripheral distribution of insulin-positive cells. Our studies have demonstrated that insulin-positive cells can be detected in monolayers obtained from human pancreata 3-4 weeks after culture. When exposed to varying concentrations of glucose, these cells secreted insulin. The development of this in vitro technique for culturing human pancreatic islet tissue could provide a model for systematically studying in vitro islet function.

Cells, Cultured↗

Primary myelodysplastic syndrome: an analysis of 56 patients.

A total of 56 patients were diagnosed as primary myelodysplastic syndrome (MDS) at Chang Gung Memorial Hospital, Kaohsiung from April 1986 to December 1991. The median age was 65 years with an equal sex ratio. All patients presented with anemia and 52% with pancytopenia. The overall median survival for the entire group was 7 months, in which the chronic myelomonocytic leukemia (CMMoL) was 7 months, and 4 months for each of the refractory anemia with excess of blasts (RAEB) or the refractory anemia with excess of blasts in transformation (RAEB-T), however, the median survival had not been reached at 27 months for refractory anemia (RA) and at 33 months for refractory anemia with ring sideroblasts (RARS). Low-does arabinosyl cytosine (Ara-C) was administered in 9 patients with RAEB and RAEB-T, but no survival benefit was noted. Infection, especially pneumonia, was the most common cause of death. In 61 febrile episodes with clinically suspected sepsis, 10 (17%) were documented to associate with bacteremia. Twelve patients (7 RAEB, 4 RAEB-T, and 1 CMMoL) evolved to acute myelogenous leukemia (AML), the median interval from diagnosis to evolution was 4.8 months. This series indicates that only two groups of FAB subtypes could be clearly separated in terms of morphological findings and clinical outcome; RA and RARS constitute a good prognostic group, whereas RAEB, CMMoL, and RAEB-T constitute a poor prognostic group.

Adolescent↗

Rhodopsin Thr58Arg mutation in a family with autosomal dominant retinitis pigmentosa.

The authors report a family in which a Thr58Arg rhodopsin mutation co-segregates with the disease phenotype of autosomal dominant retinitis pigmentosa (RP) in 16 family members. DNA sequence determination confirms the presence of the same mutation reported previously for one family apparently unrelated to the pedigree now reported. Features of RP in this family included a later onset of symptoms, with night blindness first noticed between ages 12 to 24 years. Although symptoms worsened with age, no complete blindness was observed even with advanced age. Results of psychophysical and electrophysiologic testing showed that a 19-year-old affected woman and her 65-year-old affected uncle had relatively similar extent of visual dysfunction, and that the vision of both was better than 2 of their relatives aged 37 and 53 years. This study presents a range of phenotypic similarities and differences observed between individuals whose RP appears to be caused by the same mutation.

Adult↗

Acute basophilic leukemia. A case report.

A case of acute nonlymphocytic leukemia (ANLL) with primitive basophilic differentiation is presented. The patient had no antecedent history or concomitant presence of chronic myelogenous leukemia. The leukemic blasts constituted 83% of the peripheral white blood cells and more than 90% of the marrow nucleated cells. Cytoplasmic vacuoles were found in some leukemic cells. About half the leukemic cells showed a few azurophilic granules stained with Wright's stain, whereas exhibited a faint pinkish hue around the cells without cytoplasmic granules (water-soluble granules) by Riu's stain. The cytoplasmic granules failed to be stained with peroxidase but stained positively with toluidine blue. The former result could lead one to misclassify the case as lymphoid leukemia, but the characteristic finding of basophilic cells in Riu's stain should direct one to make the diagnosis of ANLL with basophilic differentiation. The cytochemical findings of this case suggested that basophilic differentiation should be considered when leukemic cells show peroxidase-negative granules. Riu's stain and toluidine blue stain are useful to make the correct diagnosis.

Adolescent↗