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Biomedical subjects

T H Liu

Publications and source records attributed to T H Liu.

At least 19 recordsLinked to original sources

Nonfunctioning pancreatic endocrine tumors. An immunohistochemical and electron microscopic analysis of 26 cases.

Twenty-six patients with non-functioning pancreatic endocrine tumor (NFPET) were operated on during a 22-year period (1968-1990) at PUMC Hospital, Beijing. Of these, 19 were female and 7 were male with a mean age of 33 years. All these tumors, including 12 malignant and 14 benign, were solitary, and most of them were well-encapsulated. Immunohistochemical staining showed 23 (88.5%) containing 1-4 kinds of peptide hormone and 18 (69.2%) being multihormonal. In 7 of the 9 tumors subjected to electron microscopic study, various amounts of neurosecretory granules were found. Tumors of this series were clinically silent, but they contained some immunoreactive peptides, although the amount of the peptides varied from tumor to tumor.

Adenoma, Islet Cell

The role of flow cytometry and morphometry in discriminating benign from malignant nonfunctioning pancreatic endocrine tumors.

Nonfunctioning pancreatic endocrine tumor (NFPET) is a kind of tumor with high malignancy but bland in morphological features. It is impossible to predict the malignancy solely by gross and light microscopic pictures of the tumor. For the purpose of assessing the value of flow cytometry and morphometry in predicting the prognosis of NFPET, the DNA content and several morphological parameters of 26 NFPETs were determined by appropriate techniques. The results show that abnormal DNA content has no practical value in discriminating benign from malignant NFPETs; whereas the "score" obtained by combining the morphological measurements of the number of nuclei/mm2 and N/C, is of certain referential significance in predicting the malignancy of NFPET.

Adenoma, Islet Cell

[Gene expression of NGFR, EGFR, CGA, NPY in 4 neuroblastoma cell lines].

Gene expression of nerve growth factor receptor (NGFR), epidermal growth factor receptor(EGFR), chromogranin A (CGA) and neuropeptide Y (NPY) in 4 neuroblastoma cell Lines without N-myc amplification was studied by using Northern blot technique. N type cells expressed more NGFR mRNA than S type cell's and have only little or no EGFR expression. S type cells had stronger expression of EGFR mRNA than that of N type cells accompanying with only less or even no NGFR expression. The results indicated that difference of gene expression of these growth factor receptors might be due to the various directions of tumor cell differentiation. Cells differentiating toward neurons gave more NGFR expression and cells prepared to be differentiating toward other direction might give more EGFR gene expression. Various gene expression of CGA and NPY in neuroblastoma cell lines might be due to the presence of different stages of tumor cell differentiation and NGF only induced differentiation of those neuroblastoma cells ready to be differentiating to neurons afterwards.

Blotting, Northern

Detection of cellular ki-ras oncogene and Epstein-Barr viral DNA by polymerase chain reaction in situ.

A newly established technique of polymerase chain reaction (PCR) in situ is reported. The process involved the use of the PCR technique to amplify the target gene and to generate the radiolabelled products which was used as a probe to hybridize the target gene in situ. Ki-ras oncogene in human pancreatic carcinoma cell line (PC-2) and EBV DNA in Raji cell line were detected in situ by this technique with encouraging results. This technique has the advantages of both PCR and in situ hybridization, i.e., high sensitivity, quick amplification and precise localization. It is a rapid, simple, economical and reliable method.

Adenocarcinoma

[Oncogene expression and point mutation in human pancreatic adenocarcinomas].

By nucleic acid hybridization and PCR techniques, oncogene expression in normal human pancreatic tissue as well as 4 human pancreatic adenocarcinoma cell lines were studied. Additionally, c-Ki-ras gene point mutation were also detected in the paraffin embedded sections collected from 34 cases of surgical specimens resected due to pancreatic adenocarcinoma. The results showed that none of the 5 oncogenes described was expressed in the normal human pancreatic tissue, whereas, all the human pancreatic adenocarcinoma cell lines expressed c-myc and c-Ki-ras oncogenes. 28 out of 34 cases (82.4%) of human pancreatic adenocarcinomas had c-Ki-ras gene codon 12 point mutation.

Adenocarcinoma

Role of xanthine dehydrogenase and oxidase in focal cerebral ischemic injury to rat.

The role of xanthine dehydrogenase and oxidase as a source of free radicals contributing to focal cerebral ischemic injury was evaluated in Long-Evans rats after the middle cerebral artery was permanently occluded and both carotid arteries were clamped for 90 min. The fraction of xanthine dehydrogenase present as the free radical producing oxidase increased slightly from 22% in control cortex to 30% in the ischemic right cortex during the first 3 h of reperfusion and then remained relatively unchanged over the next 24 h. This increase may in part be due to entrapped plasma, which contained 4.5 +/- 0.8 nmol.min-1.ml-1 xanthine oxidase entirely in the free radical-producing form. Infarct volume was unaffected by pretreatment with 50 mg allopurinol/kg per day over 3 days before surgery but was decreased by 8% with 100 mg/kg and 24% with 150 mg/kg of allopurinol (P less than 0.05). However, inhibition of xanthine oxidase by dietary depletion of the essential molybdenum cofactor increased infarct volume by 19%, suggesting that protection by allopurinol at higher dosages was independent of xanthine oxidase inhibition. Neither xanthine oxidase present in rat brain nor circulating in plasma appears to be the primary source of oxygen radicals that contributes to infarction in focal cerebral ischemia.

Allopurinol

Brain polyphosphoinositide metabolism during focal ischemia in rat cortex.

Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting 32Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when 32Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury.

Animals

The prevalence of carcinoma in palpable vs impalpable, mammographically detected lesions.

Concern over excessive numbers of false-positive mammograms, leading to unnecessary investigations and surgical interventions, has been cited as a barrier to mammographic screening for breast cancer. We compared the biopsy results from palpable vs impalpable, mammographically detected lesions from one experienced breast surgeon's practice from July 1980 through July 1989. Overall, there were 372 biopsies in 346 women. Of 143 biopsies for palpable abnormalities, 48 (34%) yielded a primary malignant lesion. The length of the palpable cancers averaged 3.7 cm (median, 2.8 cm). Sixteen (33%) of the 48 biopsies were in patients who had positive axillary lymph nodes, and five (10%) were in patients who had distant metastases at the time of biopsy. Of 229 biopsies for impalpable, mammographically detected lesions, 72 (31%) yielded a primary breast carcinoma. Excluding 34 carcinomas that had only calcifications, the length of the mammographically detected tumors averaged 2.0 cm (median, 1.5 cm). Eleven (15%) of the 72 biopsies were in patients who had positive axillary nodes, and none were in patients who had distant metastases at the time of biopsy. The positive predictive values (number of cancers detected divided by the number of biopsies recommended) were not significantly different when comparing biopsies indicated for palpable, clinically detected (34%) vs impalpable, mammographically detected (31%) abnormalities (p = .669). However, the mammographically detected cancers were smaller, more often noninvasive (32% vs 4%), less often associated with axillary metastases (15% vs 33%), and without distant metastases (0% vs 10%).

Biopsy

Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities.

A comparative morphologic study of aortic changes with aging was conducted in different populations in an attempt to separate the effects of hypertension and atherosclerosis. Chinese and the occidental populations were chosen, as they are known to have a high prevalence of hypertension and atherosclerosis, respectively. Aortic tissue was collected from occidental (American and Australian) and Chinese populations from three geographic locations. Postmortem specimens were obtained from four fixed locations: ascending aorta (A), descending thoracic aorta (B), and abdominal aorta (suprarenal [C] and above the aortic bifurcation [D]). Histologic sections were used to measure aortic circumference, medial thickness, intimal thickness, and grade of atherosclerosis. Kidney sections were used to confirm the presence or absence of hypertension. A total of 302 cases (age range, 19 to 104 years; Male-to-female ration, 2:1) were studied: 112 Americans, 80 Australians, and 110 Chinese. Cases were divided into three age groups: 19 to 44; 45 to 64; and 65 years and older. The aortic circumference progressively decreased from sites A to D in all populations and age groups. The aortic circumference increased with age, and the increase was independent of the aortic location. When the populations were separated, however, the greater increase was at location A in the Chinese (P = .008) and locations D in the occidental (P = .13), a population contrast that was significant only in location A. Intimal thickness increased with advancing age and was maximal in the abdominal aorta. The population differences also were significant for intimal thickness and were significantly greater in the occidental population in B, C, and D locations, whereas for atherosclerosis significance was only seen in location D. Hypertension (as defined by the morphologic changes in the kidney) after adjusting for age, height, and weight resulted in no statistical significant effect on aortic circumference or on intimal thickness, but did show a significant increase in atherosclerosis score at locations B, C, and D. Also after adjusting for age, height, and weight, the Chinese had a significantly larger aortic circumference in location A compared with the occidental population, whereas in location D the occidentals with hypertension had a significantly larger circumference compared with Chinese, probably due to an interaction of atherosclerosis and hypertension. After similar adjustments, the medial thickness in locations A and C, the intimal thickness in B, C, and D, and atherosclerosis score in D were significantly greater in occidental than Chinese populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Epidermal growth factor and its receptors in human pancreatic carcinoma.

The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells.

Epidermal Growth Factor

Leukotriene B4 release and polymorphonuclear cell infiltration in spinal cord injury.

Activation of arachidonic acid occurs after spinal cord injury. Leukotriene B4 is a lipoxygenase metabolite of arachidonic acid. In a rat model of experimental spinal cord injury, we found that the leukotriene B4 content was less than the sensitivity of our assay (8 pg/mg of protein) in non-traumatized spinal cord. Leukotriene B4 was detectable in traumatized cord (mean +/- SE, 25 +/- 5 pg/mg of protein; n = 3). Release of leukotriene B4 from spinal cord slices into the incubation medium was also noted after trauma (9 +/- 1 pg/mg of protein; n = 12) and was enhanced by exposure of traumatized spinal cord slices to the calcium ionophore A23187 (375 +/- 43 pg/mg of protein; n = 12). The amount of leukotriene B4 released corresponded to the extent of post-traumatic polymorphonuclear cell infiltration determined by a myeloperoxidase assay. Results from this study suggest that the source of leukotriene B4 in spinal cord injury is infiltrating polymorphonuclear cells.

Animals

Two new human exocrine pancreatic adenocarcinoma cell lines in vitro and in vivo.

Two human pancreatic carcinoma cell lines, PC-1 and PC-2, were established from nude mice xenografts derived from metastatic pancreatic carcinomas of two patients. The two cell lines propagated continuously in vitro over 19 and 19.5 months. The cells grow in a monolayered sheet with doubling times of 47 hours for PC-1 and 58 hours for PC-2. The cells exhibited epithelial morphology and were confirmed to be malignant epithelial cell lines by morphological study, CEA and cytokeratin immunocytochemistry, flow cytometry and Con A test. The tumors caused by inoculation of cultured PC-1 and PC-2 into nude mice retained the histological and ultrastructural features of the original tumors. The findings proved that the two cell lines were human exocrine pancreatic adenocarcinoma cell lines. Chromosomal analysis together with flow cytometry data revealed that the two cell lines had the human aneuploid karyotypic features with model chromosome numbers of 48 and 66.

Adenocarcinoma

Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury.

Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.

Animals