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Biomedical subjects

J T Chen

Publications and source records attributed to J T Chen.

At least 109 records · Page 6Linked to original sources

Amino acid polymorphism and rare electrophoretic variants of G6PD from natural populations of Drosophila melanogaster.

Identifying the amino acid changes responsible for electrophoretic variants is essential to understanding the significance of allozyme polymorphism in adaptation. The amino acid mutations responsible for the common G6PD allozyme polymorphisms in Drosophila melanogaster have been recently described. This study characterizes the amino acid changes associated with 11 rare electrophoretic G6PD variants. The 11 rare electrophoretic variants result from six independent amino acid mutations. The in vivo function of the rare variants was determined in an earlier study and most variants fell into one of two function classes. It is shown here that the function of the rare variants reflects the state of the Pro/Leu mutation responsible for the A/B allozyme polymorphism in each variant. Two mutations destabilize quaternary structure resulting in shifts from tetrameric dimeric alleles, and one of these also results in a variant with in vivo function intermediate to A and B. That mutation is an aspartic-acid-to-asparagine change that is two residues away from the Pro/Leu polymorphism responsible for the A/B dimertetramer quaternary shift. Structure-function relationships based on studies of human G6PD deficiency-associated mutations predict that these last two amino acid changes fall within the protein domain responsible for NADP binding.

Amino Acid Sequence↗

Complete structures of three rice sucrose synthase isogenes and differential regulation of their expressions.

By cloning and sequencing cDNA and genomic DNA and transcription initiation site mapping, the total structures including at least 1 kb of putative regulatory sequences upstream of the transcription initiation sites of three genes encoding rice sucrose synthase isoprotomers were either newly established or amended. The third type of SS gene, RSus3, has not been found in other plants. The structures of the three genes and the gene products were compared and their evolutionary sequence was proposed. Specific probes for the three SS mRNA's were developed and used for analyzing their steady state levels at different organs and under some physiological stress conditions. It appears that RSus2 is a house-keeping gene, RSus3 is highly specific to the grain, and the expression of RSus1 shows a tendency to complement that of RSus3. A possible cause of the presence of the third rice SS gene was discussed. We also reported a novel method to synthesize single-stranded DNA for S1 mapping of a transcription initiation site associated with extended secondary structures.

Base Sequence↗

Oesophageal squamous cell carcinoma after gastrectomy for benign ulcer disease.

Of 684 patients treated for squamous cell carcinoma of the oesophagus in 1982-1993, 19 (2.8%) had previously undergone partial gastrectomy for benign ulcer disease. The average interval between gastrectomy and diagnosis of oesophageal carcinoma was 14 years. In six of the 19 (31.6%) cases the carcinoma was in the lower thoracic oesophagus, an incidence not significantly higher than the 25% in the total series. The oesophageal resectability rates were 52.6% in the gastrectomized patients and 44.4% in the total series (intergroup difference not significant). Of the ten gastrectomized patients who underwent oesophageal resection, only one had oesophagitis at the oesophagogastric junction, without significant histologic characteristics. The relationship between oesophageal squamous cell carcinoma and previous gastrectomy for benign ulcer disease may be incidental.

Adult↗

Use of recombinant Epstein-Barr virus early antigen for detection of antibody in patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and Taiwan. Serological studies revealed the close-relationship between NPC and Epstein-Barr virus (EBV). Elevated serum and saliva levels of anti-EBV antibodies are detected in patients with NPC. Therefore, Development Center for Biotechnology prepared the EBV-early antigen (EA-D) by recombinant DNA technique for screening the serum and throat washing samples from patients with head and neck cancers. METHODS: The BMRF1 gene for EBV early antigen (EA-D) was placed into the plasmid pDB18, then transformed into an Escherichia coli strain containing the lambda cI857 temperature-sensitive repressor. Heat treatment of the transformant, at exponential growth phase, inactivated the cI protein and induced an over-expression of the EA-D protein. Next, the EA-D was purified by chromatography and characterized as a protein of molecular weight 47 kDa, by sodium dodecyl sulfate-polyacry lamide gel electrophoresis (SDS-PAGE) and Western blot analysis using monoclonal anti-EA antibody and sera from patients with nasopharyngeal carcinoma (NPC). Enzyme-linked immunosorbent assay (ELISA) with the purified EA-D antigen was used to screen 129 serum and throat washing (TW) samples from patients with head and neck tumors, 24 from patients with a nonmalignant disease and 44 from normal donors. RESULTS: Experimental results indicated significantly higher positive rates of EA-D IgA (69%) and EA-D IgG (91%) in NPC sera than in the sera of patients with other head and neck tumors and normal controls. TW samples from patients with NPC also showed a higher positive rate (34%) than the other groups (7-20%). CONCLUSIONS: Results in this study demonstrate that the bacterially expressed EA-D antigen could be recognized by sera from patients with NPC and monoclonal anti-EA antibody. Thus, it has potential use in ELISA for screening EBV-related diseases such as NPC.

Antibodies, Viral↗

Intradural metastasis to the cauda equina from carcinoma of the anus.

STUDY DESIGN: This is a report of a man with carcinoma of the anus and intradural metastasis to the cauda equina. OBJECTIVE: To perform a laminectomy with tumor removal for relief of pain. SUMMARY OF BACKGROUND DATA: Only 25 cases of intradural spinal metastasis have been reported in the English literature. This is the first report of a metastatic case, moving from the carcinoma of the anus to the cauda equina. METHODS: Magnetic resonance imaging showed an ill-defined mass, with central necrosis, to the cauda equina. The possibility of intradural metastasis to the cauda equina was indicated by unique pain symptoms. RESULTS: The patient's back pain subsided after total laminectomy of L3-L5 with subtotal removal of the tumor. The residual tumor became smaller with postoperative radiation. CONCLUSION: Magnetic resonance imaging is a good diagnostic choice in this situation. The cause of the metastasis was unclear, but it was presumed to have occurred through the perineural lymphatic ducts. Laminectomy with tumor removal is feasible for relieving pain and demonstrating pathology.

Anal Canal↗

Overexpression or mutation of the p53 tumor suppressor gene does not occur in malignant ovarian germ cell tumors.

BACKGROUND: The p53 tumor suppressor gene has been well studied in epithelial ovarian cancers. However, little is known of the expression of this gene in ovarian germ cell tumors. The authors attempted to investigate whether p53 alterations occurred in this group of tumors. METHODS: Twenty-two patients with malignant ovarian germ cell tumors were included in this study. Immunohistochemical staining for p53 was performed on paraffin embedded tissue of each case. Single-strand conformation polymorphism analysis of exons 4-9 of the p53 gene was performed on 9 of the 22 tumors where genomic DNAs were obtained from the frozen tissue samples. Three tumors that revealed focal p53 positivity by immunostaining were studied further with direct DNA sequencing. RESULTS: Overexpression of p53 was not observed in all of the 22 ovarian germ cell tumors; only 3 were found to have nuclear staining in a small fraction of the malignant cells (< 5% in 1 immature teratoma, 5-10% in 2 yolk-sac tumors). Among the nine frozen tumors subjected to single-strand conformation polymorphism analysis, none revealed p53 mutation in exons 4-9. There was no p53 mutation detected by DNA sequencing of the three tumors with focal immunoreactivity. CONCLUSIONS: Alterations of the p53 tumor suppressor gene may not be associated with the pathogenesis of ovarian germ cell tumors. Instead, genetic changes such as inactivation of other tumor suppressor genes and/or activation of some protooncogenes need to be studied to determine the genetic mechanisms of the tumor development.

Adolescent↗

Serum responsiveness of the rat PCNA promoter.

Expression of proliferating cell nuclear antigen (PCNA) gene is growth-regulated. The growth dependence of the rat PCNA gene promoter activity was investigated. Cultured cells were transfected with the promoter containing plasmid and recovered for 48 h in serum-free medium to become quiescent. Cells were then cultured in serum-containing medium and harvested at certain intervals after serum-stimulation, and the promoter-directed chloramphenicol acetyltransferase activities in cell extracts were measured. The promoter used in this study contained sequences between -693 and +125 in relation to the transcription initiation site. The promoter activity was found to be serum-responsive. However, the serum-responsiveness of the promoter became less obvious when the amount of the promoter increased; meanwhile, the promoter became active in the control unstimulated (or quiescent) cells. It was suspected that the dosage effect was due to the titration of the negative regulatory factor in quiescent cells. The titration experiment with a reporterless construct as competitor for regulatory factors showed that the excess of promoter molecules reduced the promoter activity in serum-stimulated cells, while causing a transiently increase of promoter activity in quiescent cells. Based on these results, it is postulated that the serum-responsiveness of the rat PCNA promoter is controlled by both negative and positive regulatory factors. Consistent with this proposition, promoter binding proteins of 105 and 114 kDa were identified only in serum-stimulated and quiescent cells, respectively, in addition to several other promoter binding proteins (ranging from 76 to 110 kDa) which were seen in both serum-stimulated and quiescent cells.

Animals↗

Rapid detection of hemoglobin variants by mutagenically separated polymerase chain reaction (MS-PCR).

The detection of molecular defects of hemoglobin variants using mutagenically separated polymerase chain reaction (MS-PCR) was applied in this study. Using different lengths of allele-specific mutagenic primers, normal and mutant alleles of hemoglobin genes were amplified in the same reaction tube. Subsequent gel electrophoresis showed at least one of the two allelic products at the same loci or at least two of the several allelic products at different loci. We employed MS-PCR to test the following hemoglobin variants: Hb Constant Spring (Hb CS), Hb E, Hb G-Taichung, Hb J-Meinung, and Hb Kaohsiung. The results were the same as those obtained by amplified created reaction sites (ACRS) or direct sequencing. We conclude that the MS-PCR provides a rapid and simple alternative to other techniques for mutation detection in hemoglobin variants. Moreover, the principle can be extended to other genetic diseases.

Alleles↗

Isolated lateropulsion of the trunk in cerebellar infarct.

MRI in a 63-year-old male with isolated lateropulsion of the trunk disclosed an infarct in the inferior portion of the right cerebellar hemisphere, suggesting an end-zone type infarct in the lateral branch of the right posterior inferior cerebellar artery (1PICA) or a borderzone infarct between 1PICA and superior cerebellar artery. A close clinico-topographical relationship between isolated lateropulsion of the trunk and lesion in the territory of 1PICA was demonstrated.

Cerebellum↗

Rapid diagnosis of beta-thalassaemia by mutagenically separated polymerase chain reaction (MS-PCR) and its application to prenatal diagnosis.

We have developed a rapid and simple PCR-based method which is modified from the mutagenically separated polymerase chain reaction (MS-PCR) to detect the molecular defects of beta-thalassaemia. We can use this technique to amplify normal and mutant alleles of the beta-globin gene in the same reaction tube, using different-sized allele-specific primers. This mutagenesis separates the amplification reactions of alleles performed in the same tube. Subsequent gel electrophoresis shows at least one of the two allelic products at the same locus or at least two of the several allelic products at different loci. Therefore, in addition to simple handling, MS-PCR provides a within-assay quality control for the exclusion of false negative results. The five most common mutations of beta-thalassaemia and haemoglobin E which occur in the Taiwanese population were tested, and 14 prenatal samples were checked with accurate results. This method is simple, rapid and accurate, and can be used routinely in prenatal diagnosis. The principle used here can also be applied to other genetic diseases.

Base Sequence↗

Basal tail skin temperature elevation and augmented response to calcitonin gene-related peptide in ovariectomized rats.

Hyper-release of calcitonin gene-related peptide (CGRP) plays a direct and pivotal role in the induction of menopausal hot flushes (HFs), in which a drastic increase in skin temperature occurs. However, it is not possible to investigate whether CGRP induces skin temperature increase and whether skin temperature response to CGRP changes and contributes to the occurrence of HFs in postmenopausal women who are in oestrogen deficiency. By using rats' tail skin temperature (TST), a good marker to evaluate skin temperature regulation, we examined the effects of CGRP and calcitonin (3, 10 and 30 micrograms/kg, i.v.) on TST in female rats and further investigated the TST change induced by CGRP (10 micrograms/kg, i.v.) in ovariectomized (OVX) rats compared with that in sham-operated (Sham) rats. We found that CGRP, but not calcitonin, induced a TST increase in a dose-dependent manner and that the TST change induced by CGRP (0.6 +/- 0.2 degrees C for OVX rats vs 0.3 +/- 0.1 degree C for Sham rats, P < 0.05) and also the basal TST (26.0 +/- 0.2 degrees C for OVX rats vs 25.5 +/- 0.1 degree C for Sham rats) were significantly greater in OVX rats (P < 0.05). Furthermore, treatment with oestradiol (30 micrograms/kg, s.c.) for 8 days partially inhibited the augmented TST response to CGRP in OVX rats and almost completely inhibited (P < 0.05) the basal TST elevation, with the concomitant recovery of the serum oestradiol level to that in Sham rats. These results suggest that the augmented skin temperature response to CGRP and the elevation of basal skin temperature that are found in OVX rats, animals which are oestradiol deficient, may also occur in menopausal women and contribute to their HFs.

Animals↗

[Endometrial carcinoma without myometrial invasion].

Between 1974 and 1991, 621 patients with endometrial cancer were treated with hysterectomy without any preoperative treatment. Subsequent pathological examinations revealed that 92 cases had no myometrial invasion. Clinicopathological analysis was carried out in the 92 patients. The results are as follows: 1. Complete surgery was carried out in all cases except one case with intraperitoneal dissemination. The relapse rate in the 91 cases was 2.2% (2/91). The 2 cases with recurrence had grade 1 (G1) and grade 2 (G2) adenocarcinoma and both cases manifested local recurrence. 2. Of 70 cases treated with pelvic lymphadenectomy, two cases (2.9%) with G1 adenocarcinoma exhibited a single node metastasis. The metastatic site was an external iliac lymph node in both cases. Despite the lymph node metastasis, the 2 cases have exhibited no relapse. 3. None of the 92 cases showed any evidence of adnexal metastasis. The positive rate of peritoneal cytology was 13.4% (9/67). Except for one case with peritoneal dissemination who also had positive peritoneal cytology, 8 cases with positive peritoneal cytology have not developed recurrence. This study showed that some endometrial cancer patients without myometrial invasion manifest recurrence, peritoneal dissemination or lymph node metastasis. It is therefore considered that lymphadenectomy and careful follow-up are necessary in every case of endometrial cancer, even in G1 cases without myometrial invasion.

Adenocarcinoma↗

Isolated resection of proper caudate lobe for hepatocellular carcinoma in cirrhotic liver: a case report.

The caudate lobe of the liver is located between the hepatic hilum and the inferior vena cava. Resection of the caudate lobe alone, without sacrificing other parts of the liver, is a surgical challenge. An isolated resection of proper caudate lobe was accomplished here in a 64-year-old man with hepatocellular carcinoma complicated by liver cirrhosis. The post-operative course was uneventful. The patient remains free of disease two years after operation. The technique used is described to advocate isolated caudate lobectomy for a patient with cirrhosis with a caudate lobe hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Epidemiological study of head injuries in central Taiwan.

BACKGROUND: Head injury plays a major role in emergency neurosurgery and is the leading cause of neurosurgical mortality at Taichung Veterans General Hospital. Statistical data show that a similar condition exists in other teaching hospitals in the central Taiwan area, which includes more than one-quarter of the entire population and has more than one-third of the total land of Taiwan. A clinical statistical survey of head injuries in this area may provide a better understanding of the realistic situation in Taiwan. Reports on head injuries in Taipei City, Taipei area, and Hualian County are also cited for comparison. METHODS: The present study is based on a cooperative investigation of head injuries by 18 teaching hospitals in central Taiwan from July 1991 to June 1993. All patients received a neurological examination including the Glasgow coma scale (GCS), with recording by 20 Board-certified neurosurgeons. RESULTS: The 7050 cases collected included 5322 hospitalized cases, 1694 cases seen in the Emergency Room, and 34 deaths on arrival. The leading cause of head injuries was traffic accidents (5354 cases, 76.3%). Motorcycles contributed to the highest number of cases (3661, 68.4%); and trains contributed to the lowest number (8, 0.1%). Helmets were used in only 5.2% of 3503 motorcycle accidents. Based on the patients' or families' description in 4835 cases, the leading cause of the accident was careless driving (1180 cases, 24.4%). The 1088 cases of severe head injury were classified with a score less than 8 by the GCS; 498 of them died, or an 86.6% mortality (575 cases). CONCLUSIONS: Traffic accidents are the leading cause of head injuries, and motorcycles contribute to the major part of it in central Taiwan. Similar conclusions can be drawn for other areas including Taipei City, Taipei area, and Hualian County.

Accidents, Traffic↗

[Pharmacokinetic analysis of platinum in the continuous CDDP-CBDCA treatment; its relation to the changes of blood biochemistry].

Seven patients with recurrent gynecological malignancies (2 cervical, 2 endometrial, 3 ovarian) treated with CDDP at the initial chemotherapy were studied for the pharmacokinetic analysis of platinum (Pt) and changes of blood biochemistry in the continuous CDDP-CBDCA infusion therapy. All the patients were indwelled of the total parenteral nutrition catheter. A balloon type infuser (Baxter Inc., multiday type) was connected with the catheter and the drugs were infused continuously through it. CBDCA was infused continuously from day 1 through day 5 at a daily dose of 60 mg/m2, followed by continuous CDDP infusion from day 6 through day 30 at a daily dose of 2.5 mg/m2. All the patients received 3 courses of the treatment. The area under the [Pt]-time curve (AUC) of filterable Pt was as high as 60.98 +/- 8.20 mg.hr/ml (mean +/- SE), and that of total Pt 691.48 +/- 93.61 mg.hr/ml. However, the Cmax of filterable Pt was as low as around 400 ng/ml during day 1 to 6, and around 20 ng/ml during day 7 to day 30. As to the toxicity, only slight myelosuppression but no renal and gastrointestinal toxicity were observed in this therapy. The quality of life of the patients received this treatment were maintained well throughout of the therapy. Responders were evaluated as 1 CR, 2 PR, 2 NC and 1 PD. These data indicated that high AUC but low Cmax of filterable Pt by continuous CDDP-CBDCA therapy resulted in less toxicity. Further investigation was warranted to evaluate the efficacy of continuous CDDP-CBDCA therapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Time course changes in bone metabolic markers after menopause--a cross-sectional study].

To clarify the clinical significance of the measurement of bone metabolic markers in postmenopausal subjects, a cross-sectional study of 546 healthy women (215 premenopausal, 164 bilateral oophorectomized and 167 natural menopausal) was conducted. All the subjects had their lumbar bone (L2-4 mineral density measured by means of DEXA. Bone metabolic markers (bone formation markers: serum alkaline phosphatase, osteocalcin and intact osteocalcin; bone resorption markers: urine excretion of hydroxyproline, pyridinoline and deoxypyridinoline) were also evaluated. After dividing the subjects according to the length of time after menopause, the time course changes in the Z-score values for bone metabolic markers were calculated. A triphasic pattern of lumbar bone loss was seen: there was a rapid phase in the first 5 years after menopause, a plateau phase in the second 5 years and a slow phase beginning 10 years menopause. The changes in bone metabolic markers coincided closely with the rapid phase of bone loss. In the plateau and slow phases, there were no markers which significant changed greatly. One possible clinical application of bone metabolic markers is in assessing the results of treatment for postmenopausal osteoporosis.

Adult↗

Combined assay of serum levels of CA125 and CA19-9 in endometrial carcinoma.

Serum levels of CA125 and CA19-9 were examined in 225 cases with endometrial carcinoma before treatment and 32 cases with recurrent endometrial carcinoma. The positive rates in the 225 cases were 27.1% for CA125, 24.0% for CA19-9, and 38.7% for the combined assay. The serum levels of both CA125 and CA19-9 significantly increased with surgical staging. The presence of lymph node metastasis and extrauterine spread exhibited a marked influence on the serum levels of both CA125 and CA19-9. Myometrial invasion and vessel permeation also increased serum levels of CA125, whereas peritoneal cytology and adnexal metastasis exhibited no influence on CA125 levels or CA19-9 levels. Twenty-five of 33 cases who showed either more than 100 U/ml of CA125 level or more than 100 U/ml of CA19-9 level were classified as surgical stage III or IV. The combined assay demonstrated a 71.9% positive rate at the time of detection of the recurrence (65.6% for CA125, 43.7% for CA19-9). In 34.4% of the 32 recurrent cases, elevated levels of the tumor markers were the first sign of recurrence. These data indicate that the use of CA19-9 in combination with CA125 is noteworthy in the management of patients with endometrial carcinoma.

Adult↗