Biomedical subjects
Publications and source records attributed to T H Liu.
Tay-sachs disease (GM gangliosidosis), which is transmitted as autosomal recessive trait, is rare in China. Two cases of Tay-Sachs disease were diagnosed and treated in PUMC hospital during the past 7 years. The clinical features, blood hexosaminidase A level and autopsy findings are presented.
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Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to analyze c-Ki-ras codon 12 mutation in 27 fine needle aspiration biopsy (FNAB) specimens of the pancreas and its adjacent organs for the diagnosis of pancreatic adenocarcinoma. C-Ki-ras codon 12 mutation was present in 14 out of 15 cases of pancreatic adenocarcinoma, the positive rate was 93.33% (14/15); whereas no mutation was detected in those obtained from 12 patients with chronic pancreatitis, pancreatic cyst, gallbladder carcinoma, carcinoma of ampulla of Vater and gastric lymphoma. The results of this study verifies the PCR-RFLP technique as a practical, sensitive, rapid and reliable method for the detection of c-Ki-ras codon 12 mutation in the diagnosis of pancreatic adenocarcinoma.
The expression of mRNA for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), EGF receptor (EGFR) and c-erbB-2 genes and the immunoreactivity to these gene products were examined in 3 newly established human pancreatic carcinoma cell lines and their corresponding in vivo tumor lines using the Northern blot technique and the immunohistochemical method. All 3 cell lines expressed TGF-alpha, EGFR and 2 of the 3 lines expressed EGF and c-erbB-2 mRNAs. The immunohistochemical study showed immunoreactivity to EGF, TGF-alpha and EGFR in all these 3 cell lines and their corresponding in vivo tumor lines. These results indicate that the autocrine loop of EGF and/or TGF-alpha/EGFR in pancreatic carcinoma cells may be one of the important reasons for the uncontrolled growth of the pancreatic carcinoma. The c-erbB-2 overexpression in some of the cell lines may also contribute to the carcinogenesis or progression of this cancer.
From 1982 to 1992, 9 cases of clinical stage I serous adenocarcinoma of the endometrium were diagnosed and treated surgically in PUMC Hospital. Of these 9 patients, myometrial invasion occurred in 8 patients, lymphatic invasion in the myometrium was demonstrated in 7 patients and 6 patients were found to have extrauterine spread. The tumors studied in this paper confirmed the aggressive behavior of this particular histologic type of endometrial carcinoma. The pathological characteristics and differential diagnosis are presented.
The nucleotide sequences of a portion of the large-subunit mitochondrial rRNA gene of Pneumocystis carinii derived from 12 patients were examined. Five sequences were found to be identical to the prototype sequence reported by Sinclair et al. (K. Sinclair, A. E. Wakefield, S. Banerji, and J. M. Hopkin, Mol. Biochem. Parasitol. 45:183-184, 1991). Six sequences differed from the prototype sequence at one to three positions. The remaining sequence was markedly different from the prototype sequence and appeared to be a hybrid of the human and rat P. carinii sequences. The results of this study indicate the existence of multiple P. carinii strains infecting humans and suggest that coinfections of animal and human P. carinii strains in the same host are possible.
We studied the effects of long-term fish oil (FO) dietary supplementation on brain edema, polymorphonuclear neutrophil (PMN) infiltration, and infarct size in a rat stroke model. Rats were given regular rat chow with or without FO supplement (20% of total calories) for 7 weeks. Body weight did not differ between the two groups. In the FO group, an increase in eicosapentaenoic acid and a decrease in arachidonic acid content in hepatic phospholipids were significant in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine but not in the phosphoinositol fraction. Platelet activity reflected by serum thromboxane B2 levels was reduced in the FO group. Postischemic brain edema and PMN infiltration were not different between the two groups. The infarct volume was significantly greater in the FO group (controls: 96 +/- 7 mm3, n = 49; FO group: 124 +/- 6 mm3, n = 53; p = 0.0036). The greater ischemic brain injury in the FO-supplemented animals is probably related to the intraischemic hyperglycemia, which was worse in the FO group than in the control group (controls: 265 +/- 19 mg/dl, n = 14; FO group: 340 +/- 18 mg/dl, n = 16; p = 0.0079).
In order to study the inhibitory effect of antisense oligodeoxynucleotides on the growth of human pancreatic adenocarcinoma cell lines (PC-2 & PC-3), synthesized c-myc & c-Ki-ras antisense oligodeoxynucleotides (ASODN) and sense oligodeoxynucleotides (SODN) were added to the culture media of PC-2 & PC-3 cell lines. The cell growth activities after 24, 48, 72 hours of culture were estimated by cell count and 3H-TdR incorporation, and the concurrent oncogene expressions were studied by adopting reverse transcription PCR technique. Cell growth was significantly inhibited after exposure to ASODN for 24 & 48 hours. Cell growth in the c-Ki-ras ASODN group approached nearly the same level as in the control groups 72 hours after exposure, whereas cell proliferation in the c-myc ASODN medium was still being inhibited. By reverse transcription PCR technique, marked inhibition of c-myc & c-Ki-ras expression was seen in the groups after 24 & 48 hours treatment of c-myc & c-Ki-ras ASODNs. There was also down-regulation of c-myc & c-Ki-ras expression after 72 hours exposure to both oncogene ASODNs.
During a 5-year period (1986 to 1990), 7 patients with thoracic ectopic ACTH-producing tumors (4 pulmonary and 3 thymic) associated with Cushing's syndrome were diagnosed and treated in PUMC Hospital, Beijing. Among the 7 patients, 4 were male and 3 were female, with a mean age of 35.7 years. The duration of Cushing's syndrome before operation ranged from 6 months to 72 months. Histologically all tumors were typical carcinoids. Various amounts of neurosecretory granules were found in the tumor cells of all tumors by electron microscopy. Immunohistochemically all tumors were strongly positive for chromogranin A and NSE. The immunopositivity for ACTH was variable in different tumors. Some tumors were also positive for S-100, calcitonin, HCG alpha and HCG beta. By in situ hybridization technique, overexpression of chromogranin A mRNA was detected in all tumors.
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.
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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.
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.
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.
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.
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.
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.
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%).