Biomedical subjects

Tjin-Shing Jap

Publications and source records attributed to Tjin-Shing Jap.

12 recordsLinked to original sources

PubMed2006

Decrease heart rate variability but preserve postural blood pressure change in type 2 diabetes with microalbuminuria.

BACKGROUND: This study compares the cardiovascular autonomic function in type 2 diabetes with and without microalbuminuria, in order to identify the possible links between early nephropathy and diabetic autonomic neuropathy (DAN). METHODS: Cardiovascular reflex tests were performed to determine the cardiovascular autonomic function. Thirty cases of type 2 diabetes with microalbuminuria were studied for evidence of DAN to compare with a normoalbuminuric group of 56 diabetic patients. RESULTS: There was an increased prevalence of autonomic dysfunction in patients with microalbuminuria (63.3% in the microalbuminuria group vs. 40.0% in the normoalbuminuric controls, p = 0.001). These patients had lower heart rate variability during single breathing tests (6.9 +/- 4.3 vs. 9.6 +/- 3.6 beats/minute, p = 0.005), during 6 consecutive breathings (5.8 +/- 3.6 vs. 8.2 +/- 3.3 beats/minute, p = 0.005), after standing up (12.2 +/- 4.6 vs. 15.0 +/- 5.2 beats/ minute, p = 0.012), and during the Valsalva maneuver (11.3 +/- 3.5 vs. 13.2 +/- 3.6 beats/minute, p = 0.022). The heart rate variability with these stresses was revealed to be less favorable in subjects with microalbuminuria. However, blood pressure (BP) changes from the sitting to standing position were not significantly different for systolic BP (11.5 +/- 10.7 vs. 10.7 +/- 7.8 mmHg, p = 0.741) and diastolic BP (5.2 +/- 4.4 vs. 5.9 +/- 4.0 mmHg, p = 0.451) between the 2 groups. CONCLUSION: Type 2 diabetic patients with microalbuminuria have diminished heart rate variability in response to deep breathing, change of position and the Valsalva maneuver, but they preserve BP response to postural change. Therefore, microalbuminuria seems to be associated with early DAN, but not with advanced DAN.

Aged↗

PubMed2006

Clinical features and morphological characterization of 10 patients with noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS).

OBJECTIVE: Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease. PATIENTS: Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study. Six of the 10 received a gradient-guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests. RESULTS: All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of beta-cells nor an abnormal synthesis and/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX-1 and Nkx-6.1, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis-associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of beta-cell peptides to meal stimulation. CONCLUSIONS: Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from beta-cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying beta-cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral/paracrine factor(s) other than proinsulin, amylin, PDX-1, Nkx-6.1 and possibly glucagon-like peptide-1 (GLP-1) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient-guided subtotal or distal pancreatectomy be attempted.

Adult↗

PubMed2005

Insulin-like growth factor-1 increases endothelin receptor A levels and action in cultured rat aortic smooth muscle cells.

Insulin is known to cause an increase in endothelin-1 (ET-1) receptors in vascular smooth muscle cells (SMCs), but the effect of insulin-like growth factor 1 (IGF-1) on ET-1 receptor expression is not known. We therefore carried out the present study to determine the effect of IGF-1 on the binding of ET-1 to, and ET type A receptor (ETAR) expression and ET-1-induced 3H-thymidine incorporation in, vascular SMCs. In serum-free medium, IGF-1 treatment increased the binding of 125I-ET-1 to SMC cell surface ET receptors from a specific binding of 20.1%+/-3.1% per mg of protein in control cells to 45.1%+/-8.6% per mg of protein in cells treated with IGF-1 (10 nM). The effect of IGF-1 was dose-related, with a significant effect (1.4-fold) being seen at 1 nM. The minimal time for IGF-1 treatment to be effective was 30 min and the maximal effect was reached at 6 h. Immunoblotting analysis showed that ETAR expression in IGF-1-treated cells was increased by 1.7-fold compared to controls. Levels of ETAR mRNA measured by the RT-PCR method and Northern blotting were also increased by 2-fold in IGF-1-treated SMCs. These effects of IGF-1 were abolished by cycloheximide or genistein. Finally, ET-1-stimulated thymidine uptake and cell proliferation were enhanced by IGF-1 treatment, with a maximal increase of 3.2-fold compared to controls. In conclusion, in vascular SMCs, IGF-1 increases the expression of the ET-1 receptor in a dose- and time-related manner. This effect is associated with increased thymidine uptake and involves tyrosine kinase activation and new protein synthesis. These findings support the role of IGF-1 in the development of atherosclerotic, hypertensive, and diabetic vascular complications.

Animals↗

PubMed2005

Mutations in low-density lipoprotein receptor gene as a cause of hypercholesterolemia in Taiwan.

Familial hypercholesterolemia (FH) is inherited as an autosomal dominant trait that has been associated with more than 920 different mutations in the low-density lipoprotein receptor (LDLR) gene. To characterize LDLR gene mutations in the Chinese of Han descent with FH, we isolated genomic DNA from peripheral blood samples of 20 affected subjects and 50 healthy subjects with no family history of hypercholesterolemia. We used polymerase chain reaction and long polymerase chain reaction to amplify the 18 coding exons and the minimal promoter of the LDLR gene, and subjected amplicons to direct sequence analysis. We identified 6 mutations in LDLR gene, including heterozygous missense mutations I420T (ATC-->ACC), C660W (TGC-->TGG), H562Y (CAC-->TAC), and A606T (GCC-->ACC), and a heterozygous and a homozygous mutation in codon P664L (CCG-->CTG) as well as a homozygous large deletion of exons 6 to 8. The FH homozygotes manifested generalized xanthomatosis. One of the mutations we identified (C660W) was novel. In conclusion, we identified 5 missense mutations and 1 large deletion in LDLR gene, including 1 novel mutation in Han Chinese with FH in Taiwan.

Adult↗

PubMed2005

Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.

OBJECTIVE: To identify MEN1 gene mutations and characterize clinical manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1) in Taiwan. PATIENTS AND METHODS: Eight unrelated subjects (one male and seven females, age range 26-70 years) with clinical manifestations of MEN1 were analysed. In addition, 45 relatives that included 10 affected (three males and seven females, age range 32-53 years) and 35 unaffected (17 males and 18 females, age range 15-80 years) subjects were evaluated. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis were performed according to standard procedures. RESULTS: We identified heterozygous MEN1 gene mutations in all eight probands and 10 affected subjects as well as in 13 clinically asymptomatic relatives. Novel mutations included a missense mutation in a heterozygous mutation in exon 9 (GAC --> CAC) resulting in a substitution of aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon 556 of exon 10 (GAG --> TAG) resulting in a stop codon and termination (family 2); a missense mutation in exon 2 (GGG --> GAG) causing the substitution of glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion mutation in nucleotide 1200 of exon 8 resulting in frameshift and early termination (family 4). Affected subjects in families 5-7 shared the same C insertion at nucleotide 1650 of exon 10, similar to that previously described as a hotspot for mutation, and proband 8 had a previously described mutation in intron 4 of the MEN1 gene (IVS4-9 G --> A). We also found that 18 (58%) of our 31 MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical abnormalities without clinical symptoms, and nine (29%) were unaffected both clinically and biochemically. CONCLUSIONS: We have identified four novel mutations in the MEN1 gene in patients with MEN1 in Taiwan.

Adolescent↗

PubMed2004

A prospective study of glycemic control during holiday time in type 2 diabetic patients.

OBJECTIVE: In the U.K. Prospective Diabetes Study, A1C increased from 1.2 to 1.7% and fasting plasma glucose from 1.0 to 2.8 mmol/l over 10 years in type 2 diabetic patients. It is not known whether the blood glucose increase observed in long-term studies of type 2 diabetes results from small, steady increases throughout the year or from increases during discrete periods. RESEARCH DESIGN AND METHODS: To estimate the variation of actual glycemic control and its relation to holiday times, we measured A1C and fructosamine in 110 patients with type 2 diabetes. These measurements were performed four times at intervals of 4-6 weeks; therefore, glycemic change was determined for three periods: preholiday period (from between November 13 and December 20 to between December 20 and January 20), holiday period (from between December 20 and January 20 to between January 28 and February 28), and postholiday period (from between January 28 and February 28 to between March 1 and April 10). A final measurement of A1C was obtained from 90 subjects in the following December or January. RESULTS: The mean A1C increased, but not significantly, during the preholiday (increase 0.135 +/- 0.723%, P = 0.055) and holiday (increase 0.094 +/- 0.828%, P = 0.239) periods. The mean A1C decreased, but not significantly, during the postholiday period (decrease 0.022 +/- 0.588%, P = 0.695). Altogether, the A1C change during these three periods increased significantly (increase 0.207 +/- 0.943%, P = 0.024). The mean fructosamine increased significantly during the preholiday period (increase 0.151 +/- 0.460 mmol/l, P = 0.001), but there was no significant change during the holiday period (increase 0.057 +/- 0.593 mmol/l, P = 0.321). However, fructosamine decreased significantly during the postholiday period (decrease 0.178 +/- 0.448 mmol/l, P < 0.001). Altogether, the fructosamine changes during the study periods showed no significant difference (increase 0.030 +/- 0.566 mmol/l, P = 0.579). Between March or early April and the following December or January, there was no additional change in A1C (decrease 0.009 +/- 1.039%, P = 0.935) for the 90 participants who returned for follow-up treatment. CONCLUSIONS: The present study demonstrates an influence of winter holidays on the glycemic control of patients who have type 2 diabetes, and this poor glycemic control might not be reversed during the summer and autumn months. Therefore, the cumulative effects of the yearly A1C gain during the winter holidays are likely to contribute to the substantial increase in A1C that occurs every year among type 2 diabetic individuals.

Adult↗

PubMed2003

Intra-arterial calcium stimulation test for detection of insulinomas: detection rate, responses of pancreatic peptides, and its relationship to differentiation of tumor cells.

The selective intra-arterial calcium stimulation test has greatly facilitated the precise regionalization of insulinomas smaller than 2 cm, which noninvasive techniques (ultrasound [US], computed tomography [CT], magnetic resonance imaging [MRI]) often fail to localize. This study examined not only the role of the test in the localization of insulinomas, but also the responsiveness of 3 beta-cell peptides (insulin, C peptide, and proinsulin) and their relationship to the degree of differentiation of the tumor cells, using percentage decrease of both proinsulin/insulin (P/I) and proinsulin/C peptide (P/C) ratios after stimulation as indices. Ten consecutive surgically proven insulinoma patients each received an injection of calcium into the arteries supplying the pancreas after standard selective angiography and beta-cell peptide levels were measured in samples taken from the right hepatic vein before and 30, 60, 90, 120, and 180 seconds after each injection prior to operation. After surgery, the expressions of the calcium sensing receptor (CaSR) on the resected tumors were assessed by immunohistochemistry. Intra-arterial calcium stimulation with sampling either for insulin or for C peptide correctly predicted the site of insulinoma in 8 of 9 patients or in 7 of 8 patients if the 2 big malignant insulinomas were excluded; thus, the detection rate of this test was 89% and 88%, respectively. Calcium administration stimulated a marked and prompt release of insulin and C peptide simultaneously. Both peaked within 30 to 60 seconds, then declined gradually thereafter, remaining above the baseline at 180 seconds. The magnitude of increase correlated well with the corresponding percentage decrease of P/I and P/C ratios. The response of proinsulin was much less. Immunohistochemistry demonstrated variable membraneous staining for CaSR in normal pancreatic islets and in about 9% of the total normal beta cells, whereas staining in tumor cells was only minimally detectable. We conclude that selective intra-arterial calcium stimulation with hepatic venous sampling either for insulin or for C peptide is a highly sensitive method for the preoperative localization of small insulinomas. Calcium injection stimulates a brisk response of insulin, C peptide, and proinsulin simultaneously and the magnitude of increase of both insulin and C peptide appears to be correlated well with the degree of differentiation of the tumor cells. The exact mechanism by which calcium provokes the release of beta-cell peptides is less clear and whether the CaSR is involved in the mechanism of its action requires further study.

Adult↗

PubMed2003

Two novel mutations in the gene encoding thyroxine-binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan.

OBJECTIVE: Thyroxine-binding globulin (TBG) encoded by the TBG gene on chromosome Xq22 is the major transport protein, carrying approximately 75% of circulating T4. Inherited defects in TBG are associated with three phenotypes based on the level of TBG in serum of affected hemizygous males: complete TBG deficiency (TBG-CD), partial TBG deficiency (TBG-PD) and TBG excess (TBG-E). In this study, we report two unrelated Han Chinese males with complete TBG deficiency who carry different mutations in the TBG gene. PATIENTS: Two index cases of Han males who were diagnosed as having TBG deficiency on the basis of undetectable serum TBG and an additional 75 (50 males and 25 females) normal Han Chinese. MEASUREMENT: Serum thyroid hormones were measured by chemiluminescent immunoassay, thyroid autoantibodies by an agglutination test, and TSH receptor antibody and TBG by radioimmunoassay. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis of the TBG gene were performed with standard methods. RESULTS: One index case had one missense mutation in his copy of the gene, a G --> A transition in codon 52 that results in the replacement of serine by asparagine, and a known polymorphism in codon 283 (TTG --> TTt) that results in the replacement of leucine by phenylalanine. The allelic frequency of TBG-Poly allele in 75 normal Han Chinese (100 chromosomes) was 31%. A second index case was hemizygous for a nonsense mutation in codon 280 of exon 3 (TGG --> TGa). This mutation, located in the C-terminal of TBG, predicts a markedly truncated protein. CONCLUSIONS: This is the first report of complete thyroxine-binding globulin deficiency (TBG-CDT1 and TBG-CDT2) due to TBG gene mutations in Taiwan.

Case-Control Studies↗

PubMed2003

Mutations in the lipoprotein lipase gene as a cause of hypertriglyceridemia and pancreatitis in Taiwan.

INTRODUCTION: Familial lipoprotein lipase (LPL) deficiency is inherited as an autosomal recessive trait and is characterized by chylomicronemia, eruptive xanthoma, hepatosplenomegaly, and recurrent pancreatitis. AIMS AND METHODOLOGY: Two unrelated Chinese of Han descent with hypertriglyceridemia were enrolled in this study, and another six Han Chinese with no family history of hypertriglyceridemia and diabetes were recruited as normal controls. LPL activity was determined with use of an artificial substrate of 14C-trioleine and Arabic gum, and release of 14C free fatty acid was determined by the liquid-liquid partitioning system. LPL mass was measured by enzyme immunoassay. Genomic DNA was extracted from EDTA-preserved whole blood, and PCR was used to amplify the nine coding exons and the minimal promoter of the LPL gene. RESULTS: DNA sequence analysis revealed that mutations were identified in both patients; one patient had compound heterozygous mutations in codon 252 [CTG(Leu) --> GTG(Val)] and in codon 264 [TGC(Cys) --> TGa(Ter)] of exon 6, and the other patient had homozygous L252V mutation. These subjects had > or =90% reduction in LPL mass and > or =60% reduction in LPL activity. CONCLUSION: The mutated and truncated LPLs caused hypertriglyceridemia in these patients in Taiwan with hypertriglyceridemia and pancreatitis.

Adult↗

PubMed2003

Primary adrenal lymphoma manifestating as adrenal incidentaloma.

Although involvement of the adrenals by malignant lymphoma is common, primary adrenal lymphoma is extremely rare. Herein, we report a case of a 59-year-old woman with bilateral adrenal glands enlargement found incidentally on abdominal imaging. Despite of the huge size of the tumor, her adrenal function was intact. Ultrasound-guided biopsy disclosed a picture of malignant lymphoma, diffuse large B cell type. The patient received bilateral adrenalectomy and adjuvant chemotherapy, but succumbed 6 months later. We suggest that, although rare, primary adrenal lymphoma should be considered as a possible cause of bilateral adrenal incidentalomas.

Adrenal Gland Neoplasms↗

PubMed2002

A novel mutation in the intron 1 splice donor site of the cholesterol ester transfer protein (CETP) gene as a cause of hyperalphalipoproteinemia.

The exchange of cholesterol ester (CE) between lipoproteins occurs through the action of cholesterol ester transfer protein (CETP). The human CETP gene is composed of 16 exons encompassing 25 kbp on chromosome 16q13. The objective of this study was to determine whether a mutation in the CETP gene accounted for severe hyperalphalipoproteinemia in an 80-year-old subject. As a secondary objective, we also investigated the allelic frequency of D442G and Int14A mutation in 224 random Han Chinese subjects. DNA sequence analysis of the CETP gene in the patient revealed a peculiar nucleotide pattern in intron 1. To determine whether this peculiarity results in abnormally spliced mRNA, we used reverse-transcriptase polymerase chain reaction (RT-PCR) to amplify and sequence the patient's cDNA using CETP-specific primers that spanned this splice junction. Both the wild-type and mutant cDNA were detected, and the mutant cDNA showed that its 5'-splice site shifted 4 nucleotides upstream. This change results in a frame-shift and premature termination at amino acid residue 22, and thus predicts a markedly truncated protein product. Although this patient did not have either the D442G or Int14A allele, we found that the allelic frequency of D442G in 224 subjects was 4.46%. No subjects had the Int14A allele. In conclusion, a novel intron 1 splice site mutation in the CETP gene in 1 patient with hyperalphalipoproteinemia and D442G allelic frequency of 4.46% was found among a normal population in Taiwan.

Aged↗

PubMed2002

A reappraisal of the ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of Cushing's syndrome: a comparison with the standard high-dose dexamethasone suppression test.

BACKGROUND: We evaluated the diagnostic efficacy of the ovine corticotropin-releasing hormone (oCRH) stimulation test in the differential diagnosis of Cushing's syndrome and compared it with the standard high-dose dexamethasone suppression test. METHODS: Twelve healthy volunteers and 30 with Cushing's syndrome (12 Cushing's disease and 18 adrenal Cushing's syndrome) were enrolled. Plasma ACTH and cortisol levels were measured before and after an intravenous bolus of 100 microg oCRH. Plasma and urinary free cortisol were determined after standard 2-day high-dose dexamethasone suppression. RESULTS: Basal cortisol in 12 patients with Cushing's disease and 18 with adrenal Cushing's syndrome were higher than the control group (21.4 +/- 0.1 microg/dl vs. 22.3 +/- 0.5 microg/dl vs. 9.1 +/- 1.5 microg/dl; p < 0.01). In Cushing's disease, basal plasma ACTH value was significantly higher than those with adrenal disease (61.1 +/- 1.4 pg/ml vs. 6.2 +/- 4.5 pg/ml; p < 0.01). After oCRH, plasma ACTH and cortisol significantly increased, with a mean of 2.0 +/- 0.2-fold (range 1.0-2.4) and 1.6 +/- 0.1-fold (range 1.1-2.1), respectively over the basal values in patients with Cushing's disease, and 11 (90%) attained a significant ACTH (1.5-fold) or cortisol (1.2-fold) response. All except 2 (89%) with adrenal Cushing's showed no apparent change in response to oCRH. Dexamethsone suppressed urinary free cortisol by 90% in 8 (67%) with Cushing's disease, but all (100%) with adrenal Cushing's syndrome were resistant. No patient with Cushing's disease was refractory to oCRH and dexamethasone, while none with adrenal Cushing's syndrome was responsive to both. Combination of both tests could achieved a specificity of 100% for Cushing's disease and adrenal Cushing's, when these 2 tests gave concomitant positive or negative results, respectively. CONCLUSIONS: The oCRH test is a reliable examination in the differential diagnosis of Cushing's syndrome and is comparable to the high-dose dexamethasone test. A highest discrimination could be achieved when both are used.

ACTH Syndrome, Ectopic↗