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Biomedical subjects

T K Chang

Publications and source records attributed to T K Chang.

67 records · Page 4Linked to original sources

Inhibitory effect of xylamine on the uptake of [3H]norepinephrine into primary astrocyte cultures.

Primary astrocyte cultures from neonatal rat brains show a Na+-dependent, desipramine-sensitive uptake of [3H]norepinephrine ([3H]NE). Xylamine, a nitrogen mustard, attenuated this uptake of [3H]NE into the astrocytes (IC50 = 0.8 microM). The dose-dependent reduction of [3H]NE uptake by xylamine indicated competitive kinetics. However, xylamine lost the effect if the active transport inhibitor, ouabain or iodoacetate, was also incubated during the pretreatment period of if Na+ was absent. The activity of Na(+)-K(+)-ATPase in astrocytes was not modified by xylamine at the concentrations sufficient to block the uptake of [3H]NE. These findings suggest that xylamine has the ability to compete with the transport of [3H]NE into astrocytes through an effect on the carrier instead of an action on enzymatic activity.

Animals↗

Effects of toluene on the morphology of neuropeptide secretory neurons of the rat hypothalamus.

The effect of toluene on the hypothalamic hormone-secreting neurons and neurotransmitter-containing fibers in the rat was investigated by immunohistochemical methods. Multiple intraperitoneal injections of toluene (totally 7.5 ml) led to significant decreases of the neuronal numbers of vasopressin, oxytocin and neuropeptide Y in the preoptic and hypothalamic areas. The densities of vasopressin, oxytocin, norepinephrine and neuropeptide Y immunoreactive fibers of the toluene dose group decreased markedly in the median eminence. In contrast, LHRH neurons remained unchanged.

Animals↗

Superior vena cava syndrome in children with malignancy: analysis of seven cases.

Superior vena cava syndrome (SVCS) is rare in children. In Veterans General Hospital-Taipei, a total of 364 cases of SVC syndrome were diagnosed in the past 12 years. Of them only seven cases were younger than 18 years of age, ranging from 6 to 17 years, and they were all caused by mediastinal tumor. The underlying malignancy included malignant lymphoma in 4, teratocarcinoma in one and unknown in 2. The most common initial symptom was cough, followed in order of frequency by chest discomfort or neck mass. Dyspnea, orthopnea, swelling of head and neck, and venous engorgement might develop gradually within one to three weeks. Of the reported seven cases, two cases received immediate resuscitation upon arrival but expired in 1-2 hours. The other five cases received treatment with intravenous steroid as well as chemotherapy, and three cases also received committent emergent radiotherapy. Two of them expired 4 months and 2 years after treatment, respectively. Of the two surviving cases, one has received a complete course of chemotherapy and the other is still under regular chemotherapy in our hospital. Both of them are stable till now.

Adolescent↗

[Successful treatment of congenital anaplastic astrocytoma by combining vinblastine, cisplatin and etoposide: a case report].

Congenital brain tumor is a rare disease in the neonatal period. According to the literatures, they comprise only about 1% of childhood brain tumors. Among the congenital brain tumors, 10%-25% are astrocytomas. Anaplastic astrocytoma is one of the malignant glioma. The prognosis is usually not good in the childhood or adult stage. We report one case of congenital anaplastic astrocytoma who received combination chemotherapy, including vinblastine, cisplatin and etoposide following subtotal resection of tumor. After chemotherapy, he got a favorable outcome. And now, he is still no evidence of tumor recurrence for two years.

Antineoplastic Combined Chemotherapy Protocols↗

Imprinting of hepatic microsomal cytochrome P-450 enzyme activities and cytochrome P-450IIC11 by peripubertal administration of testosterone in female rats.

The influence of peripubertal exposure to physiological doses of testosterone on the adult androgen responsiveness of hepatic microsomal cytochrome P-450 was investigated. Male and female Sprague-Dawley rats were sham-operated or gonadectomized before puberty, at 25 days of age. They were injected subcutaneously with testosterone enanthate (5 mumol/kg/day) during the pubertal time period, on days 35-49. Responsiveness to this same dose of testosterone was tested by administering the compound during adulthood, on days 81-89. The females provided a model that had not been exposed to neonatal androgen imprinting, in contrast to the males. Testosterone 2 alpha-hydroxylase activity and cytochrome P-450IIC11, which are normally expressed only in adult males, were expressed in the gonadectomized females administered testosterone during puberty with no further exposure to the hormone for the next 40 days. The levels found were similar to those in the gonadectomized male group. When the combined pubertal and adult testosterone regimen was used, a synergistic effect was produced; the 2 alpha-hydroxylase activity reached control male levels in both gonadectomized and sham-operated females and, in addition, cytochrome P-450IIC11 attained control male levels in the gonadectomized females. Testosterone 6 beta-hydroxylase and erythromycin N-demethylase activities were used as indicators of the cytochrome P-450IIIA subfamily. These activities were significantly increased only in the females treated with testosterone during both the pubertal and adult periods, reaching control male levels of 6 beta-hydroxylation. A similar effect, but in the opposite direction, was found with testosterone 7 alpha-hydroxylase, an enzyme activity indicative of cytochrome P-450IIA1. A decrease in this enzyme was produced in the females administered testosterone during both time periods, resulting in levels equivalent to those found in control males. In general, a highly significant interaction was found between the pubertal and adult treatment periods for the females, indicating a chronic effect of the pubertal exposure. The experiments with castrated males did not result in synergistic interactions, although there was some evidence of an additive effect. The results of this study support the hypothesis that the peripubertal period is a time during which testosterone imprinting of both increased basal levels and adult androgen responsiveness of some hepatic cytochrome P-450 enzymes can occur in the female rat.

Animals↗

Gene synthesis, expression, and mutagenesis of the blue copper proteins azurin and plastocyanin.

Genes for the blue copper proteins Populus nigra var. italica plastocyanin and Pseudomonas aeruginosa azurin have been constructed by a stepwise procedure. The leader sequence for azurin has been placed before the genes directing plastocyanin and azurin transport to the periplasmic space when the genes are expressed in Escherichia coli. Site-saturation mutagenesis has been used to alter two copper-binding residues of azurin (Met-121 and His-46) and Met-92 of plastocyanin. While the plastocyanin mutants do not appear to bind copper, the azurin variants all bind copper and show characteristic type I blue copper centers. In particular, the electronic spectra reflect the dominance of the charge transfer interaction between copper and the thiolate of Cys-112, being relatively insensitive to changes in Met-121 or His-46. In contrast, removal of Met-121 appreciably alters the EPR spectra of the mutants, although, to a first order, the spectra of all mutants are themselves similar, suggesting a more distorted geometry around copper in the mutants than in the wild type.

Amino Acid Sequence↗

Immunocytochemical study of small round cell tumors in routinely processed specimens.

Fourteen commercially available monoclonal antibodies were used to examine, by the indirect immunoperoxidase technique, 20 formaldehyde solution-fixed, routinely processed bone marrow biopsy and surgical biopsy specimens from a group of small round cell tumors with bone marrow involvement, including 6 neuroblastomas, 4 rhabdomyosarcomas, 3 Ewing's sarcomas, 3 Burkitt's lymphomas, and 4 small-cell carcinomas of the lung. Eight of 14 monoclonal antibodies worked well on the routinely processed sections. Antidesmin (D33) (Dako Corp, Santa Barbara, Calif) and anti-muscle actin (HHF35) showed specific immunostaining in all 4 rhabdomyosarcomas included in this study. Anti-epithelial membrane antigen immunoreactivity was positive in all small-cell carcinomas of the lung. Anti-leukocyte common antigen (Dako) showed positive immunostaining in lymphomas and did not immunoreact with nonhematopoietic tumors. However, it was important to be aware that some lymphomas may not have been labeled with anti-leukocyte common antigen. All 6 neuroblastomas showed a positive immunoreactivity with anti-chromogranin A (LK2H10) and a weak reaction with antisynaptophysin (SY38). Panels of commercially available monoclonal antibodies, including anti-leukocyte common antigen, anti-epithelial membrane antigen, antidesmin (Dako), anti-muscle actin, and anti-chromogranin A, appear to be most useful in the differential diagnosis and staging of small round cell tumors on routinely processed biopsy specimens.

Actins↗

Non-Hodgkin's lymphoma in childhood--five years survey in VGH-Taipei.

From January 1981 to January 1986, 34 children between 2 and 14 years of age were diagnosed as non-Hodgkin's lymphoma by the Rapport's classification at the Department of Pediatrics of Veterans General Hospital, Taipei, R.O.C. These patients were retrospectively analysed. There was male predominance with a male to female ratio of 2.4:1. The most common symptom was the palpable mass (29 cases, 85.3%) involved the neck and abdomen equally. All the cases were diffuse patterns, DUL (diffuse undifferentiated lymphoma) and DPDL (diffuse poorly differentiated lymphoma) both were the common subtypes of histological patterns. Twenty-eight cases (82%) were in the advanced stage (stage III and IV). The incidence of BM and CNS involvement was 56% and 29.4%, respectively. CNS involvement demonstrated a higher mortality of 100%. Surgery, radiation, and chemotherapy were mainly used for stage I-II and chemotherapy for stage III-IV. The 3-year survival rate of the whole series was 26.5%, and stage I, II, III, and IV was 100%, 50%, 33%, 9%, respectively. The causes of death were CNS involvement (10 cases, 40%), extensive involvement (7 cases, 28.0%), and sepsis (3 cases, 12.0%). This study shows that NHL in children are usually diffuse rather than follicular in histological patterns, often present a palpable mass involved the cervical or abdominal area, and commonly are widespread and tend to disseminate early.

Adolescent↗

Seroimmunity to poliomyelitis in hospital personnel.

Neutralizing antibody titers to poliovirus type 1, 2 and 3 were examined in paired serum specimens obtained from 43 female hospital personnel and laboratory workers at Veterans General Hospital. Before vaccination, 23.2% of those studied did not have neutralizing antibodies to one or more types of poliovirus, and 4.6%, 13.9% and 7.0% lacked serum neutralizing antibodies to poliovirus type 1, 2 and 3, respectively. In a comparison of the serological responses evoked by oral poliovirus vaccine in the same persons, a striking difference in antibodies was shown in the geometric mean titers and no lack of antibodies was found after oral poliovaccine immunization. Therefore immunization with oral poliovirus vaccine should be considered in the future as to improved protection for such high risk people.

Adult↗

Thanatophoric dysplasia type I.

Thanatophoric dysplasia is a sporadic, nearly always lethal congenital skeletal dysplasia. It is characterized by shortening of the limbs, a severely small thorax, macrocephaly, and platyspondyly. There are two major subtypes: a short, curved femur characterizes type I, and a straighter femur with cloverleaf skull characterizes type II. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR-3) gene have been identified in both subtypes, which suggest that thanatophoric dysplasia is a genetically homogenous skeletal disorder. Most affected neonates die of respiratory failure, due to narrow thorax with pulmonary hypoplasia. Antenatal sonographic diagnosis is feasible in the second trimester of pregnancy, but differentiating thanatophoric dysplasia from non-lethal skeletal disorders is very important. At the present time, however, prenatal genetic screening seems unpractical.

Female↗

Eosinophilic granuloma of sternum. Report of one case.

A rare case of solitary eosinophilic granuloma of the sternum in a 5-year-old boy is reported. He presented anterior chest pain and a nodular, somewhat tender mass over the sternum. Chest x-ray, tomography, CT scanning of the sternum and total body Gallium scanning revealed an isolated lytic lesion 5 cm below the sternal angle. An excisional biopsy of the mass showed the typical histologic appearance of eosinophilic granuloma. An isolated eosinophilic granuloma of sternum is rarely reported in the English literature. The differential diagnosis of sternal tumors and a review of eosinophilic granuloma of sternum is discussed.

Child, Preschool↗

1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) modulates rat liver microsomal cyclophosphamide and ifosphamide activation by suppressing cytochrome P450 2C11 messenger RNA levels.

The alkylating anticancer drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; lomustine) is frequently administered to cancer patients as part of a combination chemotherapy regimen. Previous studies have indicated that CCNU treatment of adult male rats leads to prolonged decreases in liver cytochrome P450 (CYP)-mediated enzyme activities. Because the alkylating agent prodrugs cyclophosphamide and ifosphamide are known to be activated by liver cytochrome P450 enzymes, the potential for interaction between CCNU and these oxazaphosphorines was examined. Treatment of adult male rats with a single dose of CCNU (30 mg/kg i.p.) resulted in a progressive loss of liver microsomal cyclophosphamide and ifosphamide hydroxylation activities in vitro (30-60% decrease after 7-27 days). The individual liver P450 forms modulated by CCNU were then identified using P450 form-specific microsomal testosterone hydroxylase assays. CCNU treatment was found to decrease substantially CYP2C11-dependent testosterone 2 alpha-hydroxylase activity (80-90% decrease after 14 or 27 days), but it did not affect CYP3A2-dependent testosterone 6 beta-hydroxylase activity. It only modestly decreased CYP2A2-mediated testosterone 15 alpha-hydroxylase activity. The reduction in CYP2C11 activity was not associated with a decline in liver microsomal NADPH-cytochrome P450 reductase activity, but rather was caused by a complete suppression of CYP2C11 mRNA levels. In contrast to other alkylating agents, such as cisplatin, which is known to feminize the overall expression profile of gender-specific liver enzymes, CCNU did not increase levels of the female-predominant liver enzymes steroid 5 alpha-reductase and CYP2C7, nor did it deplete circulating testosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗