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Biomedical subjects

S N Chow

Publications and source records attributed to S N Chow.

71 records · Page 4Linked to original sources

Generation of monoclonal antibodies to human prolactin and applications in solid-phase immunoassays.

Monoclonal antibodies specific to human prolactin were generated by an improved hybridoma technique. Following immunization with hormone conjugated with hemocyanin and cell fusion, hybrid cells were first cultured in a semisolid medium containing methylcellulose and later transferred to liquid medium for subculture. Out of 1500 colonies that were initially recovered in one single cell fusion experiment, 300 were shown to exhibit affinity to human prolactin by enzyme-linked immunosorbent assay and radioimmunoassay. Finally, nine monoclonal antibodies having high affinity and specificity to human prolactin were selected for further evaluations. From the results of a cross-matching procedure, one pair of antibodies reacting with discrete antigenic determinants of human prolactin was identified. Using a pair of monoclonal antibodies, the solid phase sandwich immunoradiometric assay and enzyme immunoassay were designed. The sensitivity of these 1-h immunoassay procedures for the determination of human prolactin was 2 ng/ml.

Animals↗

The placental transfer and concentration difference in maternal and neonatal serum uric acid at parturition: comparison of normal pregnancies and gestosis.

The maternal uric acid (MUA) and neonatal uric acid (NUA) levels were measured simultaneously at parturition in three groups of pregnancies: group I - 83 cases of normal pregnancies, group II - 7 cases of mild gestosis and group III - 12 cases of severe gestosis, totaling 102 cases. Umbilical venous blood samples were taken in all of the cases. Maternal venous blood samples were obtained from 69 patients in group I, 6 cases in group II, and 12 cases in group III. The correlation coefficients of MUA and NUA values were 0.90, 0.91, and 0.95 (all p less than 0.01) in the three groups, respectively, and 0.93 in total series (p less than 0.0001). The high correlation and minimal concentration difference between MUA and NUA in either normal or gestosis suggested free transfer of uric acid via placenta in both directions. Moreover, not only MUA but also NUA levels were significantly different among normal and gestosis groups, and both MUA and NUA showed higher levels in accordance with the severity of gestosis. Both MUA and NUA had negative correlation with birth weight (BW), one-minute apgar score (AS-1) and five-minute apgar score (AS-5). It implied that the uric acid levels at parturition might provide as a reference index for fetal outcome in pregnancy with gestosis.

Female↗

Effect of estrogen (Premarin) replacement therapy on serum level of total estrogen and urinary excretion of calcium and hydroxyproline in postmenopausal Chinese women.

The study subjects included a total of 30 postmenopausal Chinese women, including 14 natural menopausal women, 13 castrated menopausal women and 3 post-irradiated menopausal women. Premarin 1.25 mg/day was given orally for 3 weeks and off one week, repeated for 6 cycles. Fasting morning urine and blood samples were collected before hormone treatment and at the end of 3 weeks, 11 weeks, and 23 weeks of Premarin therapy. Serum total estrogen level was measured by radioimmunoassay. Urinary calcium and creatinine were measured by atomic absorption and Jeffe's reaction, respectively. The concentration of urinary hydroxyproline was determined by Kivirikko's method. After Premarin therapy, the mean concentration of serum total estrogen increased 3 to 4 times from the pretreatment level of 71.7 pg/ml. On the other hand, the mean value of calcium/creatinine (Ca/Cr) molar ratio dropped down from 0.249 to 0.098. The mean value of hydroxyproline/creatinine (HOPr/Cr) molar ratio was reduced from 0.028 to 0.012. In view of the hormonal and biochemical changes after Premarin therapy, it is concluded that estrogen (Premarin) replacement should be effective in the treatment of enhanced bone loss or osteoporosis in postmenopausal women. The relationship of estrogen and calcitonin in the regulation of bone metabolism is also discussed.

Adult↗

Studies of monoclonal antibodies against human chorionic gonadotropin. II. Applications of human chorionic gonadotropin monoclonal antibodies on immunoassays.

Monoclonal antibodies generated against human chorionic gonadotropin (hCG) were utilized in radio- and enzyme-immunoassays of this reproductive hormone in biological fluids. One of the monoclonal antibodies, beta-4D6, was shown to have extremely high affinity (Ka = 8 X 10(10) M-1)) and high specificity (less than or equal to 0.6% LH cross-reactivity) to beta-subunit of hCG and whole hCG. It was used in competitive radioimmunoassays (RIA) for the determination of low levels of serum hCG. An excellent correlation was obtained concerning the assay results between the monoclonal antibody-based system and others using conventional polyclonal anti-sera. In combination with another discrete hCG monoclonal antibody, solid-phase sandwich radiometric and enzyme immunoassays were established. These immunoassays could easily be performed, and they offer sensitivity and efficacy of hCG determination comparable to those of conventional ones.

Animals↗

Applications of monoclonal antibodies in solid-phase immunoassays of human luteinizing hormone.

Monoclonal antibodies to human luteinizing hormone (hLH) were generated by a modified hybridoma technique. Out of forty hybrid cell lines that were shown to secrete antibodies reacting with hLH, LH35 and LH40 were further characterized biochemically and immunologically. LH35 was found to secrete immunoglobulin G1 antibody specific to the alpha-subunit of LH, whereas that of LH40 was beta-subunit specific. Association constants between the antibodies and LH were determined to be 2 X 10(8) and 1 X 10(9) M-1, respectively, by using competitive radioimmunoassay and Scatchard plots. Monoclonal antibodies from LH35 and LH40 were purified from the respective ascites fluids by ammonium sulfate fractionations and DEAE ion-exchange chromatography. The purified alpha-subunit-specific antibody of LH35 was immobilized on polystyrene balls (6 mm in diameter), whereas purified LH40 antibody was conjugated with horseradish peroxidase or labeled with iodine-125. Solid-phase radio- and enzyme immunoassays were designed to measure relatively low concentrations of LH (2-100 mIU/ml). The LH surge during the midcycles of women with normal menstrual cycles could easily be detected from daily urine or serum specimens by a 1-h assay procedure. It is proposed that this new LH immunoassay procedure can be routinely used for predicting ovulation of women with normal menstrual cycles.

Animals↗

Increased catecholamine levels in cord venous plasma of distressed fetuses.

The concentrations of catecholamines in cord venous plasma were measured by trihydroxyindole fluorimetric assay in four fetuses with normal fetal heart rate (FHR) and three distressed fetuses with late deceleration of pathologic FHR. The concentrations (nmol/l) of norepinephrine and epinephrine in normal fetuses were 40.3 +/- 7.9 (mean +/- SD) and 5.4 +/- 1.5, respectively, whereas those in distressed fetuses were 156.8 +/- 48.0 and 12.1 +/- 4.5, respectively. In normal fetuses about 88% of total catecholamines consisted of norepinephrine, the remaining 12%, epinephrine. The ratio of norepinephrine to epinephrine in distressed fetuses (12.9) was thus higher than the ratio in normal fetuses (7.5). Higher levels of total catecholamine concentrations were associated with the presence of late deceleration of pathologic FHR pattern, low one-minute Apgar score, low umbilical arterial pH value (pH less than 7.20), and fetal hypertriglyceridemia (greater than 48 mg/100 ml). The relationship between fetal hypertriglyceridemia and elevated concentration of cord plasma total catecholamines is elucidated and the physiologic significance of increased secretion of catecholamines in distressed fetuses is discussed.

Apgar Score↗

Serum triglyceride levels in newborns and mothers at parturition.

From August 1980 to March 1981, paired cord venous blood and maternal antecubital venous blood were measured for triglyceride concentrations with the enzymatic method of triglyceride G-3-PDH UV end point assay, using the Hitachi Model 716 autoanalyser. The mean value of cord serum triglyceride concentrations in the cohort of 100 normal newborns was 28 ng/100 ml and the cut-off point of P95 was 48 mg/100 ml. In normotriglyceridemic newborns and hypertriglyceridemic newborns the mean values were 29 mg/100 ml and 66 mg/100 ml, respectively. However, the mean values of the corresponding triglyceride concentrations of maternal blood were not remarkably different among these 3 groups; they ranged from 190 to 193 mg/100 ml. The cord blood triglyceride level was much lower than that of maternal blood levels, with a ratio of 15% in the cohort of normal population of newborns and mothers. These findings showed that the cord serum triglyceride level was independent of the maternal serum triglyceride concentration and was of fetal origin. The relative impermeability of the placenta to this serum constituent and the lack of utilization of fat as a major source of energy in the period of normal intrauterine fetal life may, in part, account for the low serum triglyceride level in cord blood.

Female↗

Cord blood hypertriglyceridemia in Chinese newborns: an index of fetal distress.

Cord serum triglyceride concentrations in 214 Chinese newborns were measured at birth with the Hitachi Model 716 autoanalyzer using the G-3-PDH UV end point method. The mean and the 95th percentile value in a normal population of 100 newborns were found to be 28 mg/100 ml and 48 mg/100 ml, respectively. Using 48 mg/100 (P95) as a cut-off point, maternal-fetal factors were evaluated in 35 hypertriglyceridemic and 35 normotriglyceridemic newborns. A significant association was demonstrated between high cord serum triglyceride levels and toxemia, overterm, meconium-stained amniotic fluid, deceleration of fetal heart rate, intrauterine growth retardation, low one-minute Apgar score (less than or equal to 7), and low umbilical arterial pH (less than 7.20). These findings pointed out that cord serum hypertriglyceridemia was an index of fetal distress and associated with many unfavorable intrauterine conditions. They also suggested that hypertriglyceridemia might be related to the activated sympathetic nervous system and the enhanced release of catecholamines.

Adipose Tissue↗

Detection of tumor-specific antigens in human mucinous cystadenocarcinoma of the ovary by immunodiffusion.

Rabbit antiserum to a tissue extract of human mucinous cystadenocarcinoma of the ovary reacted with tissue extracts of normal ovary and various ovarian malignancies, and ascitic or cystic fluids of ovarian origin by Ouchterlony double gel diffusion and precipitin inhibition techniques. The tumor-associated antigen(s) of mucinous cystadenocarcinoma, which were demonstrated by Ouchterlony double diffusion, were not present in tissue extract of pooled normal ovaries and cystic fluid of benigh tubo-ovarian cyst. An organ-associated tumor antigen as well as the type-specific tumor antigen may exist in mucinous cystadenocarcinoma of the ovary. The mucinous cystadenocarcinoma was not very immunologically different but was distinguishable from serous cystadenocarcinoma and other types of ovarian cancer by double gel diffusion. Precipitin-inhibition reactions demonstated that the adsorbed antiserum to human ovarian mucinous cystadenocarcinoma mixed with tissue extracts of dysgerminoma and serous cystadenocarcinoma, and ascitic fluid of papillary embryonal adenocarcinoma of the ovary could not eliminate the specific precipin line developed with tissue extract of mucinous cystadenocarcinoma.

Antigens, Neoplasm↗

Primary ovarian cancer.

Sixty-six patients with primary ovarian cancer were treated at National Taiwan University Hospital from 1981 to 1985. About 21% of the patients were in stage I, 18% in stage II, 50% in stage III and 11% in stage IV. The distribution of histologic types included 73% epithelial, 15% germ cell, 9% gonadal stroma, and 3% of non-specific mesenchymal origin. The ages at diagnosis ranged from 8 to 83 years. Peak incidence was noted between 50-59 years. Mean ages for epithelial, non-epithelial, and germ cell ovarian cancers were 52, 29, and 22 years, respectively. Most (47%) of the patients were treated by surgery plus chemotherapy. Complete surgical removal of the tumor mass was done for all 14 patients with stage I ovarian cancer. Bilateral salpingo-oophorectomy plus total abdominal hysterectomy was performed in 67% of stage II, 40% of stage III, and no stage IV case. The rates of occult bilaterality in the contralateral ovary for stage I to IV were 0%, 25%, 29% and 100%, respectively. Survival in ovarian cancer is a function of clinical stage and histologic type. The 2-year survival rates for stage I to stage IV were 71%, 67%, 33%, and 0%, respectively. The 2-year survival rate was 78% for non-epithelial ovarian cancer, and 26% for epithelial ovarian cancer.

Adolescent↗

Measurement of human chorionic gonadotropin by carboxyl terminal peptide assay in patients with cervical neoplasm.

The aim of this study was to investigate whether human chorionic gonadotropin (hCG) is produced by preinvasive cancer and the early stages of invasive cancer. One hundred and fifty-two patients with either various grades of preinvasive cervical carcinoma or microinvasive carcinoma, and 46 normal women used as controls, were enrolled in this study. A carboxyl terminal peptide beta-hCG (CTP-beta-hCG) assay with a sensitivity of 0.2 mIU/mL was used to measure serum levels. The results showed that the serum beta-hCG levels among normal control, preinvasive carcinoma and microinvasive carcinoma patients were not statistically different. Among the factors tested, including the interval since the last menstrual period, age, menopausal status, contraception method and diagnosis, serum hCG levels only correlated with the first factor. Preinvasive cervical carcinoma and microinvasive carcinoma did not result in significantly increased hCG secretion. At present, the CTP-beta-hCG assay is of limited value in the diagnosis of these diseases.

Adult↗

Primary ovarian cancer at National Taiwan University Hospital: 1980-1989.

BACKGROUND: Ovarian cancer is a silent killer. Most of the patients came with advanced stages. The retrospective review here was for a better understanding of the current situation of ovarian cancer patients treated at National Taiwan University Hospital. METHODS: One hundred and eighty-seven patients with primary ovarian cancer were treated at National Taiwan University Hospital from 1980 to 1989. Medical records were reviewed thoroughly. The WHO histological classification and FIGO staging system (1987) were used. RESULTS: The ages at diagnosis ranged from 2 to 87 years. Peak incidence was noted between 50-59 years. According to the WHO histological classification, the distribution of histological types included 79.1% epithelial, 4.3% sex-cord stromal tumors, 0.5% lipid cell, 12.8% germ cell, and 3.2% non-specific soft tissue origin. Based on FIGO staging system, 31.6% of the patients were in stage I, 11.2% in stage II, 40.6% in stage III and 16.6% in stage IV. Mean ages for common epithelial, non-epithelial, and germ cell ovarian cancers were 49, 26, 23 years, respectively. Cytoreductive surgery was done in 47.4% of stage I, 23.8% of stage II, 15.8% of stage III, and 12.9% of stage IV. The leading treatment modality was surgery plus chemotherapy, which was performed in 50.3% of whole series. Survival in patients with ovarian cancer is a function of clinical stage and histologic type. The 5-year observed survival rates for stage I to IV were 76.3%, 59.9%, 9.1%, and 4.3% respectively. The 5-year survival rate was 29.4% for epithelial ovarian cancer, 51.4% for non-epithelial ovarian cancer, and 64.5% for germ cell tumors. CONCLUSIONS: The prognosis and survival rate are still unsatisfactory despite the various modalities of treatment. Further improvements need the development of methods for early detection and multiple modalities of therapy.

Adolescent↗

Molecular biology of human ovarian cancer.

It has been proposed that epithelial ovarian cancers are of unifocal origin and arise from a single cell. Many alterations occur during the multistep carcinogenesis including interaction of peptide growth factors, activation of protooncogenes, and loss of tumor-suppressor genes. Increased activity of TGF-alpha and decreased activity of TGF-beta may contribute to the development of many ovarian cancers. Loss of TGF-beta responsiveness has been associated with the downregulation of c-myc expression in the development of ovarian cancer. Alternative expression of many oncogenes including ras, erbB2 and c-myc, were detected in many studies. p53 mutation was detected in 50% of advanced ovarian cancer, suggesting that loss of tumor-suppressor gene function facilitates transformation. Serum parameters like AFP, CEA, CA-125, IAP, LDH, SA, TGF-alpha, and M-CSF have been used as ovarian tumor markers. None of these biochemical markers is presently consistent and specific enough to be an early detection for ovarian cancers.

Biomarkers, Tumor↗

Multiple pulmonary chemodectomas in a child: results of four different therapeutic regimens.

PURPOSE: Chemodectomas (or paragangliomas) are rare tumors of neuroendocrine chemoreceptors, such as the carotid body. This report describes a case of multiple pulmonary chemodectomas in an adolescent and discusses the results of four therapeutic regimens. PATIENTS: At 15 years of age, the patient had cough and fatigue. Investigation revealed numerous 1- to 2-cm diameter nodules throughout both lungs. Biopsy revealed multiple pulmonary chemodectomas of uncertain malignant potential. No extrapulmonary primary site could be found. RESULTS: Because of deteriorating pulmonary function, she was treated with courses of etoposide-cisplatin and subsequently somatostatin without effect. She finally responded to a course of doxorubicin and streptozocin. She is currently maintained on interferon-alpha 2B but her measured vital capacity continues to fall slowly, reflecting increased tumor growth. Because there is still no evidence of extrapulmonary spread, she is considered to be a candidate for lung transplantation. CONCLUSIONS: A doxorubicin-streptozocin combination produced a temporary remission of this patient's multiple pulmonary chemodectomas.

Adolescent↗