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Biomedical subjects

C N Huang

Publications and source records attributed to C N Huang.

At least 19 recordsLinked to original sources

The anti-tumor effect and mechanisms of action of penta-acetyl geniposide.

Gardenia, the fruit of Gardenia jasminoides Ellis, has been widely used to treat liver and gall bladder disorders in Chinese medicine. It has been shown recently that geniposide, the main ingredient of Gardenia Fructus, exhibits the anti-tumor effect. In this review, we discuss the anti-tumor effect and possible mechanisms of a derivative from Gardenia Fructus, penta-acetyl geniposide ((Ac)5GP). It has been demonstrated that (Ac)5GP plays more potent roles than geniposide in chemoprevention. (Ac)5GP decreased DNA damage and hepatocarcinogenesis induced by aflatoxin B1 (AFB1) by activating the phase II enzymes glutathione S-transferase (GST) and GSH peroxidase (GSH-Px). It reduced the growth and development of inoculated C6 glioma cells especially in pre-treated rats. In addition to the preventive effect, (Ac)5GP exerts its actions on apoptosis and growth arrest. Treatment of (Ac)5GP caused DNA fragmentation of glioma cells. (Ac)5GP induced sub- G1 peak through the activation of apoptotic cascades PKCdelta/JNK/Fas/caspase8 and caspase 3. Besides, p53/Bax signaling was suggested to be involved in (Ac)5GP-induced apoptosis, though its downstream cascades needs further clarified. (Ac)5GP has also been shown to inhibit DNA synthesis of tumor cells. It arrested cell cycle at G0/ G1 by inducing the expression of p21, thus suppressing the cyclin D1/cdk4 complex formation and the phosphorylation of E2F. The phosphorylation status of p53 on serine 392 correlated with the process of growth arrest. Evidences from the in vivo experiments showed that (Ac)5GP is not harmful to liver, heart and kidney. In conclusion, (Ac)5GP is highly suggested to be an anti-tumor agent for development in the future.

Animals↗

The clinical implications of telomerase activity in upper tract urothelial cancer and washings.

OBJECTIVE: To measure telomerase activity in upper tract urothelial carcinomas (as renal pelvic tumours comprise nearly half of all kidney tumours in Taiwan, a much higher percentage than in other countries) and to determine whether telomerase activity could be used as an additional diagnostic marker in exfoliated cancer cells present in upper tract urothelial washing fluids, thus providing earlier diagnosis and treatment. Materials and methods Telomerase activity was assessed using the telomeric repeat amplification protocol assay in tissue samples from 31 upper tract urothelial carcinomas (from 29 patients). The feasibility of identifying cancer using telomerase activity in exfoliated cancer cells in 17 upper tract urothelial washing samples was also investigated. RESULTS: Telomerase activity was found in 30 (97%) of the 31 upper tract urothelial cancer tissue samples; telomerase activity was detectable in 95% of superficial cancers and in all 11 invasive tumours. The sensitivity of measuring telomerase activity was 100% for grade 1, 93% for grade 2 and 100% for grade 3 tumours. In contrast, telomerase activity was detected in only two (8%) of 26 normal adjacent tissue samples. When the telomerase activity of urothelial washing fluid was compared with that in the corresponding tumours, there was compatible telomerase activity in 15 of the 17 samples. Telomerase activity was more sensitive than voided urine cytology (15%) and washing fluid cytology (53%). In addition, the telomerase activity was high in metastatic lesions. CONCLUSION: Telomerase activity is present in most upper tract urothelial cancer tissues and may be present at an early stage of carcinogenesis. Telomerase activity can be detected in exfoliated cells in urothelial washing fluids in a high proportion of patients with upper tract urothelial cancer. These results suggest that measuring telomerase activity in the exfoliated cancer cells obtained from urothelial washing could be a potentially useful addition to the conventional diagnostic tools used to identify patients with upper tract urothelial carcinoma.

Biomarkers, Tumor↗

Quantitative sensory testing and risk factors of diabetic sensory neuropathy.

The goal of this study was to identify risk factors for diabetic peripheral sensory neuropathy in type 2 diabetes mellitus in a Chinese population. Peripheral sensory neuropathy was detected by quantitative sensory testing (5.07/10 g monofilament, neurometer and 128-Hz Riedel Seiffert graduated tuning fork). Those who had two or more abnormal quantitative sensory testings were defined as having diabetic sensory neuropathy. Of the 558 non-insulin dependent diabetes mellitits subjects, 62 (11.1%) had peripheral neuropathy. In 59 (10.6%) detection was by monofilament testing, 45 (8.1%) by graduated tuning fork, and 189 (33.9%) by neurometer. In a multivariate logistic regression model, age and insulin therapy were significantly associated with peripheral neuropathy. Age, serum triglyceride, height, and fasting plasma glucose were independently associated with large fiber neuropathy. Our results confirm the previously identified multiple risk factors of diabetic neuropathy. Different quantitative sensory testings detect different nerve fiber defects. The weak correlation between these tests indicates the need to use more than one test in screening for diabetic neuropathy.

Aged↗

Screening for the Gly40Ser mutation in the glucagon receptor gene among patients with type 2 diabetes or essential hypertension in Taiwan.

As a major counterregulatory hormone of insulin, glucagon plays an important role in regulating glucose homeostasis through its binding to the glucagon receptor. Recently a missense mutation in the glucagon-receptor gene (Gly40Ser) was found to be associated with type 2 diabetes in France and Sardinia, with a frequency as high as 4.6% and 8.3%, respectively. This mutation was also found to be associated with essential hypertension in the white population with a frequency of 5.4%. To investigate the role of this mutation in the pathogenesis of type 2 diabetes and essential hypertension in Taiwanese population, we screened 121 normal controls, 213 unrelated subjects with type 2 diabetes, and 107 unrelated subjects with essential hypertension by use of polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). None of the Taiwanese subjects recruited in the study had this receptor mutation. Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.

Amino Acid Substitution↗

Emphysematous pyelonephritis: imaging diagnosis and follow-up.

We conducted the study to evaluate the efficacy and roles of different imaging modalities in the diagnosis and follow-up of emphysematous pyelonephritis (EPN) and to correlate imaging findings with clinical outcome. Retrospective analysis of the imaging studies and clinical outcome were performed in 28 consecutive patients with EPN. They were all initially treated with CT-guided percutaneous drainage (PCD). The imaging studies performed included plain abdominal radiography (KUB) (n = 28), sonography (US)(n = 24), intravenous urography (IVU)(n = 5), retrograde pyelography (RP)(n = 20) and computed tomography (CT)(n = 28). Follow-up imaging studies included CT(n = 23) and renal scintigraphy (n = 15). The sensitivities of detecting abnormal gas in EPN on KUB and US were 66% and 88%. The mortality rate was 11%, not associated with different types, stages or renal involvement. On the follow-up CT performed within one month of PCD, type I EPN evolved into type II in 86% of the cases. On the long-term follow-up CT, renal atrophy and focal scarring were revealed in the diffuse and focal renal involvement of EPN. The mean split renal function shown on the follow-up scintigraphy was 30%. We concluded KUB and US were valuable for screening EPN, although CT was the most specific and sensitive. Follow-up CT studies not only demonstrate the response of treatment but also depict the different courses and the results of different types and renal involvement of EPN, although not associated with mortality rate.

Adult↗

Sera from patients with scleroderma inhibit fibroblast micromotions monitored electrically.

OBJECTIVE: To investigate scleroderma fibroblast behavior, and the effect of different human sera on fibroblast behavior, we established a model using the newly developed electrical biosensor, electrical cell-substrate impedance sensing (ECIS). METHODS: Cellular locomotion, defined as cellular micromotion, measured by ECIS indicates the dynamic vertical motion of a given group of cells. The junctional resistance (Rb) between adjacent cells and the average height (h) between basal cell surface and substratum derived from ECIS were quantified for dermal fibroblasts obtained from patients with scleroderma and normal controls. The cellular micromotions of both scleroderma and normal control fibroblasts were compared in the presence of different human sera, including those from patients with scleroderma, systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) and from normal individuals. RESULTS: The Rb and h levels for scleroderma and normal fibroblasts were 2.7 omega.cm2, 150 nm and 0.8 omega.cm2, 303 nm respectively. The micromotions of scleroderma fibroblasts were more active than those of normal fibroblasts. Sera from patients with scleroderma can inhibit the micromotions of normal fibroblasts but not those of scleroderma fibroblasts, while sera from patients with SLE and SS have no inhibitory effect on either normal or scleroderma fibroblast micromotions. CONCLUSION: We have demonstrated the previously unrecognized characteristics of dermal fibroblasts and sera derived from patients with scleroderma. It is possible that in vivo activities cause scleroderma fibroblasts to display active cellular micromotions, while sera from patients with scleroderma inhibit the micromotions of normal fibroblasts. The use of ECIS technology has also provided a new approach to the study of scleroderma.

Aged↗

[Torsion of the appendix testis].

The differential diagnosis of an acute scrotum includes spermatic cord torsion, torsion of a testicular appendage, torsion of spermatocele, epididymitis, orchitis, trauma, hernia, testicular segmental infraction and tumor. Among these, torsion of appendix testis could got dramatic improvement if accurately diagnosed and treated. 5 patients of torsion of appendix testis have been identified in our hospital in the recent 5 years. Ages ranged from 9 to 13 years old (mean age 11). The lesions were on the right side in 2 cases and left side in 3 cases. Duration of scrotal pain ranged from 2 to 7 days (mean of 4 days). The urine analyses were normal in all cases. The white blood counts were all within normal limits with mean of 5.72 x 10(3)/ul. No abnormality in passing urine or other infectious sign could be detected. Doppler ultrasonography or nuclear medicine testicular scan were performed selectively due to clinical availability. The result was equivocal and did not support a definite diagnosis. All 5 cases received surgical treatment. The necrotic testicular appendix was excised and reactive hydrocele treated. All the patients were discharged from the hospital the day after operation and recovered quickly. The pathological report revealed congestion and extensive hemorrhagic necrosis of the testicular appendix. Advances in technology have been helpful in improving the accuracy of diagnosis but technology is not infallible and an over reliance on it can also result in misdiagnosis. Various reports supporting the use of scrotal ultrasound in evaluating cases of acute scrotum pain. Ultrasonography has definitely helped in detecting scrotal pathology but its limitations need to be appreciated. Because of the difficulty of making an accurate diagnosis in acute scrotum, misdiagnosis and delayed operation offer result in disappointment of testis salvage rates. We have supported a policy of early scrotal exploration in any case suspicious of torsion of appendix testis.

Child↗

[Studies on the application of antifreeze proteins in cryopreservation of rice suspension cells].

AFP from winter flounder was utilized in cryopreservation of plant cells. During cryopreservation of rice suspension cells by two-step method, AFP at 0.01 mg/ml damaged the cells extremely. The data obtained at relatively high concentration, however, decreased the variability of survival rate. During vitrification of rice cells, AFP at 0.2 mg/ml enhanced the viability. However, high concentration AFP (> 5 mg/ml) decreased the recovery rate. Studies indicated that the results of application of AFP in cryopreservation were closely related to the concentration of cryoprotectant. The amount of ice crystal in environment, the concentration of AFP and cryoprotectant, and the composition of plasma membrane were several key factors affecting the results of AFP application. In mechanism analysis, the authors suggested that on one hand AFP can interact with ice crystal, which inhibits ice recrystallization and prevent the cells from devitrification. On the other hand, AFP also can interact with cell membrane, resulting in the ice growth around the plasma membrane.

Antifreeze Proteins↗

Autoimmune IDDM in a sporadic MELAS patient with mitochondrial tRNA(Leu(UUR)) mutation.

We report a 28-year-old young male with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) presenting with two previous episodes of stroke-like manifestation, lactic acidosis and mitochondrial cardiomyopathy. He was also affected with insulin-dependent diabetes mellitus (IDDM), as diagnosed by the experience of diabetic ketoacidosis (DKA), and dependence on insulin therapy. On admission, the serum lactate level was found to be increased to 5.4 mmol/l, and plasma glucose level to 7.9 mmol/l with haemoglobin A1c 8.4%, while he was using insulin 26-30 units per day. Physical examination revealed a short stature male of height of 150 cm and weight of 49 kg. Mild mental retardation with bilateral sensorineural hearing impairment was observed. After glucagon stimulation, C-peptide levels rose from 0.46 nmol/l to 0.53 nmol/l, indicative of impaired insulin secretion. Anti-glutamate decarboxylase (anti-GAD) antibody was positive. In addition, human leucocyte associated antigen (HLA) typing showed DR3 and DR4, suggesting the strong contribution of autoimmunity to the pathogenesis of IDDM in this patient. Moreover, the result of a treadmill exercise test was positive due to inferior wall myocardial ischaemia. Cardiac catheterization and endomyocardial biopsy disclosed a normal coronary angiogram and confirmed the diagnosis of mitochondrial cardiomyopathy. Molecular genetic analysis of his family revealed a sporadic occurrence of mitochondrial DNA (mtDNA) mutation at base pair (bp) 3243. The degree of heteroplasmy of mtDNA mutation from a total of 19 passages of skin-derived fibroblasts from this patient showed a slightly downward trend. This extremely rare case of sporadic MELAS syndrome with autoimmune IDDM harbouring mtDNA mutation highlights the possible pathogenetic role of mtDNA mutations in autoimmune disease.

Adult↗

Changes in the activities of mitochondrial enzymes in the progress of tumorigenesis of bladder cancer.

To investigate changes in the activities of mitochondrial enzymes in the progress of tumorigenesis of bladder cancer, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen was administered orally to male Sprague-Dawley rats for eight weeks. The urinary bladders were harvested periodically for the evaluation of tumorigenesis. The activities of NADH cytochrome c reductase (NCCR), succinate cytochrone c reductase (SCCR) and cytochrome c oxidase (CCO) were measured. The NCCR and SCCR activities elevated significantly by the exposure of BBN and decreased rapidly when BBN was withdrawn. However, the CCO activity increased and reached plateau at 18 weeks in spite of the discontinuance of BBN. The results indicated that the NCCR, SCCR and CCO activities were significantly elevated in the tumorigenesis. However, the CCO enzyme may be more related to the progress of tumorigenesis of bladder cancer.

Animals↗

Autoantibodies to thyroid peroxidase in patients with type 1 diabetes in Taiwan.

OBJECTIVE: Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD). Genetic susceptibility to autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about the situation in the Chinese population. We have, therefore, investigated the prevalence of anti-thyroid peroxidase (anti-TPO) in type 1 diabetic patients, and compared the effect of anti-glutamate decarboxylase (anti-GAD) on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Taiwan. SUBJECTS AND METHODS: Two hundred and forty-three subjects with type 1 diabetes mellitus and seventy unrelated normal controls were recruited for the detection of anti-TPO. Two hundred and seventeen sera from two hundred and forty-three type 1 diabetic patients were tested for anti-GAD. RIA and immunoprecipitation were used for anti-TPO and anti-GAD detection respectively. RESULTS: The intra-assay and interassay coefficients of variation of anti-TPO detected by the RIA method ranged from 5.5% to 11.1%. Among 243 type 1 diabetic patients, 53 (21.8%) were positive for anti-TPO. Compared with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female:male, 99:91 vs 37:16 respectively). Among the type 1 diabetic patients with thyroid autoimmunity, anti-TPO tended to occur in those of older age or with long-standing disease. The frequency of anti-GAD was 45.6%, (99 of 217), without gender preponderance (males:females, 18.0% vs 27.61%). Compared with those with negative anti-GAD, no significant difference of anti-TPO positivity for the type 1 diabetic patients with positive anti-GAD was found. CONCLUSION: Our data indicated that the RIA method for anti-TPO detection is sensitive and precise for routine clinical use. The presence of anti-TPO in 21.8% of our type 1 diabetic patients confirmed the strong association of ATD and type 1 diabetes mellitus without ethnic differences. The absence of correlation between anti-TPO and anti-GAD in our type 1 diabetic patients suggested genetic heterogeneity in the role of autoimmunity of type 1 diabetes mellitus and ATD among races.

Adolescent↗

RET protooncogene mutations in patients with apparently sporadic medullary thyroid carcinoma.

We examined RET protooncogene mutations in sporadic medullary thyroid carcinoma (MTC), using polymerase chain reaction (PCR)-based sequencing. DNA was extracted from tumor tissue and peripheral blood leukocytes of seven unrelated individuals with apparently sporadic MTC. Oligonucleotide primers were selected to amplify exons 10, 11, 13, 15, and 16 of the RET protooncogene, to examine the sequences of codons 609, 611, 618, and 620 of exon 10, codon 634 of exon 11, codon 768 of exon 13, codon 883 of exon 15, and codon 918 of exon 16. Direct DNA sequencing from PCR products was then performed. The results showed that one patient had a somatic mutation at codon 918 (ATG-->ACG), causing a Met-->Thr substitution. One patient had a de novo germline mutation at codon 634 (TGC-->CGC), causing a Cys-->Arg substitution. Another patient had a germline mutation at codon 634 (TGC-->TTC), causing a Cys-->Phe substitution. In the remaining four cases, no RET mutations were found. Unexpectedly, two offspring of the patient (a female) with a germline mutation at codon 634 (TGC-->TTC) harbored homozygous alleles for the mutation; because the father did not carry this mutation, the other affected allele was suspected to have resulted from a de novo germline mutation of paternal origin. One of these offspring was subsequently diagnosed as having MTC. Our findings suggest that all patients with apparently sporadic MTC should be screened for the RET protooncogene by molecular analysis to detect occult or de novo multiple endocrine neoplasia 2 (MEN 2) or familial MTC. This would allow early treatment of affected family members.

Adult↗

Germline RET proto-oncogene mutations in two Taiwanese families with multiple endocrine neoplasia type 2A.

To elucidate the germline RET proto-oncogene mutations in Taiwanese families with multiple endocrine neoplasia type 2A (MEN 2A), we extracted DNA from peripheral blood leukocytes of 28 members of two families with MEN 2A. Oligonucleotide primers for exons 10 and 11 were used to analyze the nucleotide sequence of codons 609, 611, 618, and 620 of exon 10, and codon 634 of exon 11 of the RET proto-oncogene. Two fragments of genomic DNA were amplified by polymerase chain reaction (PCR). The amplified PCR products were separated and purified from primers and free nucleotides in agarose gels, and the expected 187-bp and 234-bp bands were cut from the gels and sequenced. Thirteen family members in the two MEN 2A kindreds had mutations in codon 634 of exon 11. In kindred 1 (15 members available for this study), a heterozygous codon 634 mutation in nine members and a homozygous codon 634 mutation in one member led to the substitution of Phe (TTC) for Cys (TGC). Three members of kindred 2 (13 members available for this study) had a heterozygous base pair change in codon 634, which led to the substitution of Arg (CGC) for Cys (TGC). In this study, we found two mutation events occurring in two MEN 2A kindreds and also discovered a homozygous point mutation in one woman that led to heterozygous mutations in all of her children.

Drosophila Proteins↗

Percutaneous drainage in the treatment of emphysematous pyelonephritis: 10-year experience.

PURPOSE: We investigated the effect of percutaneous drainage for the treatment of emphysematous pyelonephritis. MATERIALS AND METHODS: A retrospective analysis was done of 25 patients with emphysematous pyelonephritis who were treated initially with computerized tomography (CT) guided percutaneous drainage during a 10-year period. The patients were concomitantly treated with antibiotics, fluids, and correcting blood glucose and/or ureteral obstruction. We also compared our results of percutaneous drainage to CT findings. RESULTS: CT identified 12 patients with emphysematous pyelonephritis who had gas with little fluid and 13 who had gas with renal or perirenal fluid collections. In 20 of 25 patients (80%) antibiotic therapy combined with percutaneous drainage constituted the only treatment required. Three patients (12%) whose clinical status improved after percutaneous drainage subsequently underwent elective nephrectomy without further complications. Two patients (8%) died of multiple organ failure. There was no correlation between the gas patterns of emphysematous pyelonephritis and initial success with the antibiotics and percutaneous drainage. There were no recurrences and no complications during a followup of 1 to 10 years (mean 5). Mean duration of treatment was 5.54 weeks (range 1 to 12.6). CONCLUSIONS: CT is an efficient imaging method for diagnosis, guiding the drainage procedures and monitoring response to percutaneous drainage of emphysematous pyelonephritis. Antibiotic therapy combined with CT guided percutaneous drainage of emphysematous pyelonephritis is an acceptable alternative to antibiotic therapy with surgical intervention.

Adult↗

SS-A/Ro antibodies in Chinese patients with systemic lupus erythematosus and Sjögren's syndrome.

Serum from 53 patients with systemic lupus erythematosus (SLE) and 23 patients with primary Sjögren's syndrome (SS) were studied for anti-52-kDa SS-A/Ro, anti-60-kDa SS-A/Ro, and anti-SS-B/La antibodies by immunoblotting and enzyme-linked immunosorbent assay (ELISA). By immunoblotting, anti-SS-A/Ro was detected in 16 (30%) patients with SLE and 17 (74%) patients with SS. Anti-SS-B/La was detected in 22 (41%) patients with SLE and 15 (65%) patients with SS. Serum from 14 of the 16 SLE patients with anti-SS-A/Ro reacted with the 60-kDa protein and 15 serum samples from these patients recognized the 52-kDa protein. Serum with anti-60-kDa SS-A/Ro alone was not found. Serum from all of the 17 SS patients with anti-SS-A/Ro reacted with the 52-kDa protein, whereas serum from only two of these patients recognized the 60-kDa protein. By ELISA, the frequency of anti-SS-A/Ro (antibodies to the 60-kDa and/or 52-kDa of SS-A/Ro proteins) in patients with SLE and SS was 43/53 (81%) and 15/23 (65%), respectively. Anti-48-kDa SS-B/La was found in 28% and 48% of SLE and SS patients, respectively. Serum from 77% of SLE patients and 48% of SS patients reacted with the 60-kDa SS-A/Ro protein. Serum from 45% of SLE patients and 52% of SS patients reacted with the 52-kDa SS-A/Ro protein. Patients with SLE had significantly higher titers of antibodies to 60-kDa SS-A/Ro compared with patients with SS. Anti-SS-A/Ro and anti-SS-B/La are common in both SLE and SS. The different reactivities of anti-52-kDa and anti-60-kDa antibodies in serum from patients with SLE and SS may represent differences in conformation-dependent epitopes of SS-A/Ro autoantigens.

Adult↗

An unusual testicular metastasis from transitional cell carcinoma of the ureter: a case report.

Testicular tumor metastasis from transitional cell carcinoma (TCC) of the ureter is very rare. Herein, we report a case who presented with a palpable mass of left testis, after he underwent radical nephroureterectomy and bladder cuff excision and adjuvant radiotherapy and chemotherapy for the TCC of left ureter tumor for 5 months. We performed left radical orchiectomy and histology revealed a TCC identical to the original ureteral tumor. In a review of the literature, we found this case was the second case of metastatic testicular tumor from the ureteral TCC. In patients presenting the symptom of a palpable testicular mass, if they are known to have a ureteral TCC, metastatic neoplasm should be considered in the differential diagnosis, even if in the absence of other systemic metastasis.

Carcinoma, Transitional Cell↗