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Biomedical subjects

T C Chen

Publications and source records attributed to T C Chen.

At least 145 records · Page 8Linked to original sources
PubMed1996

Induction of vitamin D receptor mRNA expression in psoriatic plaques correlates with clinical response to 1,25-dihydroxyvitamin D3.

Psoriasis is a skin disorder characterized by hyperproliferation of epidermal keratinocytes. 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) and its analogs have been shown to inhibit keratinocyte proliferation in vitro and to be therapeutically effective for the treatment of psoriasis. Some patients with psoriasis, however, do not have a favorable response to 1 alpha,25 (OH)2D3 therapy. To evaluate the differential responsiveness to 1 alpha (OH)2D3 treatment, we examined the expression of vitamin D receptor mRNA in psoriatic lesions by reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase as an internal control. In this double-blind clinical trial, we recruited 18 patients who received topical treatment of 1 alpha,25(OH)2D3 (15 microgram/g Vaseline) or placebo on separated psoriatic lesions for 8 weeks. In patients who showed >90% clinical improvements of their psoriatic lesions with 1 alpha,25(OH)2D3 (n=9), an increase of 130+/-37% in vitamin D receptor mRNA level was observed in 1 alpha,25(OH)2D3-treated lesions when compared with the corresponding placebo controls. There was no increase in vitamin D receptor mRNA level in the lesions treated with this drug in patients who did not respond to the treatment. These data suggest that the antiproliferative activity of 1 alpha,25(OH)2D3 is closely associated with the expression of its cognate receptor.

Base Sequence↗
PubMed1996

Gamma unit facility: concept genesis, architectural design and practical realization.

The physical creation of a gamma unit facility requires the development of a broad-perspective multidisciplinary plan. The primary goal is radiosurgical treatment of intracranial lesions in a functional environment. The practical realization of a facility optimally designed for patient treatment is dependent on factors which include the facility setting, architectural goals, radiation safety requirements, and patient and medical team needs. This necessitates combined intellectual resources from neurosurgery, radiation oncology and physics, anesthesia, radiology, nursing, administration, and architectural and engineering teams. We undertook the development of a gamma unit facility which optimized the ergonomics and efficiency of patient evaluation, care and treatment, given the instrument requirements. This general plan based on our experience can be used for the development of other gamma unit facilities.

Clinical Protocols↗
PubMed1996

Efficacy and safety of topical calcitriol (1,25-dihydroxyvitamin d3) for the treatment of psoriasis.

Plaque-type psoriasis has been successfully treated with topical calcitriol, but there has been no long-term follow-up study of the safety and efficacy of this calciotropic hormone. In a single-centre study, patients with plaque or erythrodermic psoriasis were enrolled in a double-blind, right/left comparison, placebo-controlled study, and received 1.5 micrograms of calcitriol (15 micrograms/g of Vaseline) per day, or a placebo consisting of Vaseline alone. A subset of these patients (n = 22), with at least 25% involvement, applied 0.1 g of calcitriol ointment/50 cm2 on an area of from 2,500 to 5,000 cm2. Of the 84 patients enrolled in the double-blind control study, 96.5% responded to topical calcitriol therapy, compared with 15.5% whose lesions improved with Vaseline alone, after 2.4 months. After completion of the double-blind study, 22 patients applied calcitriol ointment (15 micrograms/g Vaseline) to all of their lesions (up to 10 g of calcitriol ointment; 150 micrograms calcitriol lesions showed either excellent or moderate clearing in 90.9% of all cases. The remaining 9.1% of cases showed slight improvement of their lesions. No abnormalities in calcium metabolism were noted in any of the patients using topical calcitriol. None of the patients experienced any local cutaneous side-effects, including six patients who applied calcitriol ointment to the face. Topical calcitriol is safe and effective for the treatment of psoriasis.

Administration, Cutaneous↗
PubMed1996

Safety and efficacy of oral calcitriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis.

Plaque-type psoriasis has been successfully treated with oral calcitriol, but there has been no long-term follow-up on the safety and efficacy of this calciotropic hormone for psoriasis. In a single centre study, patients were enrolled in an open trial to evaluate the efficacy and safety of oral calcitriol for psoriasis. Of the 85 patients who received oral calcitriol, 88.0% had some improvement in their disease; 26.5, 36.2 and 25.3%, had complete, moderate and slight improvement in their disease, respectively. The mean baseline psoriasis area severity index score (PASI) of 18.4 +/- 1.0 was reduced to 9.7 +/- 0.8 and 7.8 +/- 1.3 after 6 and 24 months on oral calcitriol therapy. Serum calcium concentrations and 24 h urinary calcium excretion increased by 3.9% and 148.2%, respectively, but were not outside the normal range. Bone mineral density remained unchanged. The clearance of creatinine decreased by 13.4% from baseline during the first 6 months of treatment, and thereafter, remained unchanged after 3 years of follow up. An evaluation of creatinine, inulin and paraaminohypurate (PAH) clearance was performed in eight patients. After 6 months on oral calcitriol, there was a 22.5% decline in creatinine clearance but no significant changes were observed in either inulin or PAH clearance, suggesting that calcitriol alters creatinine metabolism or secretion but does not affect renal function. Oral calcitriol is effective and safe for the treatment of psoriasis.

Administration, Oral↗
PubMed1996

Hypoxemia in a cirrhotic patient caused by hepatopulmonary syndrome: a case report.

Hepatopulmonary syndrome (HPS) is the triad of liver disease, pulmonary vascular dilatation, and abnormal arterial oxygenation. We report a case with progressive orthodeoxia and platypnea who was proven to have HPS after serial investigations, including autopsy. This 61-year-old male is a case of alcoholic liver cirrhosis without any documented cardiopulmonary disorders before. However, he suffered from progressive dyspnea in his last one-year life. During that period, progressive severe hypoxemia, orthodeoxia and platypnea were detected. Serial non-invasive diagnostic approaches, including two-dimensional contrast enhanced echocardiography and technetium-99m labeled macroaggregated albumin (MAA) lung perfusion scanning, were performed and showed positive evidence of intrapulmonary shunting. Direct evidence of intrapulmonary vascular dilatation was finally proven by autopsy. Although this syndrome is not rare, clinical awareness of the association between liver disease and arterial oxygen desaturation is still inadequate. We report a case proved by typical clinical manifestation and complete investigation and review the literature to emphasize this important disorder.

Cyanosis↗
PubMed1996

Squamous cell carcinoma of the ampulla of Vater: a case report.

A wide variety of neoplastic lesions may involve the ampulla of Vater, but squamous cell carcinoma has not been reported. Here we report a case of squamous cell carcinoma of papilla Vater. A 72-year-old Chinese female was manifested by obstructive jaundice and biliary tract infection. Duodenoscopic study revealed a polypoid mass with deep and broad ulcer on the ampulla of Vater. Histological examination revealed a metastatic squamous cell carcinoma. The gynecologist had examined the patient carefully and revealed a negative tumor survey. Other sources were also intensively studied but which revealed nothing. The patient developed biliary tree infection after endoscopic retrograde cholangiopancreatic study so that percutaneous transhepatic cholangiography & drainage was performed. Pseudomonas aeruginosa and Enterococcus were cultured from the drainaged bile. Radiotherapy was used and the bleeding was halted temporarily but the patient later expired due to persistent bleeding.

Aged↗
PubMed1996

Malakoplakia of urinary tract: report of two cases with emphasizing the histologic spectrum and the morphogenesis of Michaelis-Gutmann bodies.

Two cases of urinary tract malakoplakia, one in right kidney and the other one in urinary bladder, were reported. Both cases affected middle-aged female patients with long-term urinary tract infection. Their clinical presentation simulated a neoplasm. The diagnosis entirely depended on pathologic examination. The former case also extensively involved the retroperitoneum, liver and duodenum. The latter case was unusually associated with Pseudomonas infection. Electron microscopy showed that the morphogenesis of Michaelis-Gutmann bodies occurred within the phagolysosomes. Initially, small myelin-like figures-containing phagolysosomes were undergoing to fuse to form a large one. Then, the membranous fragments and myelin-like figures served as nucleation sites. The nucleation sites could be multiple in the same phagolysosome. Needle shaped crystalline material began to deposit by unknown mechanism. Finally, mature Michaelis-Gutmann bodies were well formed. But no bacteria were identified. The two cases were successfully managed with surgical resection then sulfamethoxazole-trimethoprim treatment. Finally, it was emphasized that frozen section of tumor biopsy avoided unnecessary radical surgery in the latter case.

Female↗
PubMed1995

Identification of soluble protein phosphatases that dephosphorylate voltage-sensitive sodium channels in rat brain.

Rat brain sodium channels are phosphorylated at multiple serine residues by cAMP-dependent protein kinase. We have identified soluble rat brain phosphatases that dephosphorylate purified sodium channels. Five separable forms of sodium channel phosphatase activity were observed. Three forms (two, approximately 234 kDa and one, 192 kDa) are identical or related to phosphatase 2A, since they were 85-100% inhibited by 10 nM okadaic acid and contained a 36-kDa polypeptide recognized by a monoclonal antibody directed against the catalytic subunit of phosphatase 2A. Immunoblots performed using antibodies specific for isoforms of the B subunit of phosphatase 2A indicate that the two major peaks of phosphatase 2A-like activity, A1 and B1, are enriched in either B' or B alpha. The remaining two activities (approximately 100 kDa each) probably represent calcineurin. Each was relatively insensitive to okadaic acid, was active only in the presence of CaCl2 and calmodulin, and contained a 19-kDa polypeptide recognized by a monoclonal antibody raised against the B subunit of calcinerurin. Treatment of synaptosomes with okadaic acid to inhibit phosphatase 2A or cyclosporin A to inhibit calcineurin increased apparent phosphorylation of sodium channels at cAMP-dependent phosphorylation sites, as assayed by back phosphorylation. These results indicate that phosphatase 2A and calcineurin dephosphorylate sodium channels in brain, and thus may counteract the effect of cAMP-dependent phosphorylation on sodium channel activity.

Animals↗
PubMed1995

1,25-dihydroxyvitamin D3: a novel agent for enhancing wound healing.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), has diverse effects in a variety of tissues and cell types, including skin. Since 1,25(OH)2D3 affects both fibroblast and keratinocytes, we evaluated the effect of 1,25(OH)2D3 on wound healing. We investigated the effect of the topically applied 1,25(OH)2D3 or vehicle on the healing of cutaneous wounds in rats in a blinded manner. Wound areas were measured by planimetry technique. Healing was expressed as the percentage of the original wound area that was healed. 1,25(OH)2D3 at concentrations between 5 and 50 ng/day caused a dose-dependent acceleration of healing. Time course and specificity studies indicated that 1,25(OH)2D3 specifically promoted healing between 1-5 days after wounding as compared with vitamin D (0.5 microgram/day), which showed no significant improvement over control. Our results suggest that 1,25(OH)2D3 and its analogues may be a new class of compounds that could be developed to enhance wound healing.

Animals↗
PubMed1995

Pharmacokinetics of promazine in patients with hepatic cirrhosis--correlation with a novel galactose single point method.

We examined promazine pharmacokinetics in nine patients with hepatic cirrhosis and in six healthy subjects. A specific and sensitive HPLC method was used to measure promazine concentrations in plasma, plasma water (free drug), red blood cells, and urine after oral administration of promazine (2 x 50 mg tablet). There were highly significant reductions in total plasma clearance (p < 0.01), free drug total plasma clearance (p < 0.01), metabolic clearance (p < 0.01), metabolic clearance of free drug (p < 0.01), and fraction bound (p < 0.01) in the cirrhotic patients. The elimination half-life and the area under the plasma concentration-time curve were significantly increased (p < 0.001 and p < 0.05, respectively) in the cirrhotic patients. However, the overall excreted promazine in urine, time to the promazine peak concentration, distribution half-life, renal clearance, apparent volume of distribution, and the promazine concentration ratio between plasma and red blood cells were not different. Thus caution is needed in using promazine for patients with hepatic cirrhosis. A newly developed galactose single point (GSP) method was applied to quantitatively measure the residual liver function in cirrhosis patients and successfully correlated it with promazine elimination half-life (r = 0.770, p < 0.01), total plasma clearance of free drug (r = 0.899, p < 0.005), metabolic clearance of free drug (r = 0.902, p < 0.005), and plasma protein binding (r = 0.822, p < 0.005). GSP may be a convenient index for promazine routine dosage adjustment in patients with liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Absence of p53 gene mutation and infrequent overexpression of p53 protein in hepatoblastoma.

Ten cases of hepatoblastoma were studied for overexpression of p53 protein by immunohistochemistry and for possible p53 gene mutation by single strand conformation polymorphism (SSCP) analysis and direct DNA sequencing of the polymerase chain reaction products. Only one case of the macrotrabecular type at stage IV showed overexpression of p53 protein. No DNA mobility shift was found in any of these cases studied by SSCP analysis. DNA sequencing performed on the case showing overexpression of p53 protein revealed no mutation within exons 5 to 8. The associated adrenal cortical carcinoma of the same case also showed overexpression of p53 protein, but no mutation of the p53 gene. These results indicate that mutation of the p53 gene is infrequent in hepatoblastoma. This observation supports the view that mutation of the p53 gene is not as important in the oncogenesis of childhood neoplasms as in adult cancers.

Base Sequence↗
PubMed1995

New anastomotic gun for biofragmentable anastomotic ring in low anterior resection.

PURPOSE: The biofragmentable anastomotic ring remains difficult to use for low rectal anastomosis. The authors report their experience of clinical application of the biofragmentable ring in low anterior resection with a newly designed instrument. METHODS: In this series, 31 patients underwent sphincter-preserving low anterior resections for rectal tumors from May 1993 to November 1994. With the assistance of a self-developed anastomotic instrument (biofragmentable anastomotic ring gun), biofragmentable ring anastomoses were performed following low anterior resection. RESULTS: There was no operative mortality. One patient had clinical evidence of anastomotic leakage. In postoperative follow-up, there was no anastomotic stenosis or incontinence. CONCLUSION: Therefore, we believe biofragmentable ring rectal anastomosis is a safe and reliable alternative to other anastomotic methods in rectal surgery.

Adult↗
PubMed1995

Endocardial mapping of ventricular tachycardia in the intact human ventricle. III. Evidence of multiuse reentry with spontaneous and induced block in portions of reentrant path complex.

OBJECTIVES: This study was conducted to characterize the functional nature of the reentrant tract responsible for ventricular tachycardia due to ischemic heart disease. BACKGROUND: A zone of slow conduction forming the return path is though to form a critical component of the reentrant mechanism in ventricular tachycardia. Despite its importance, detailed knowledge of the return path is rare in clinical studies. METHODS: Multielectrode arrays were used intraoperatively to obtain unipolar and high gain bipolar recordings of left ventricular endocardium in patients undergoing map-directed surgical ablation of ventricular tachycardia. A total of 224 local electrograms were analyzed for each tachycardia. RESULTS: Of 10 consecutive patients undergoing intraoperative cardiac mapping, detailed recording of the return tracts of eight ventricular tachycardias were obtained in three patients. The recordings demonstrated that return tracts can be complex and extensive, with multiple paths of entry and exit. Potential and actual alternate paths were observed. Spontaneous and induced block occurred within portions of the complex. Intermittent block in one of two paths of entry resulted in intermittent cycle length changes of the tachycardia without a change in configuration. Block in one exit path resulted in a shift to alternative exit paths, with dramatic changes in ventricular activation and tachycardia configuration. Termination of the tachycardia could result from block close to the entrant or exit portion of the return tract. Different tachycardias were seen to share common portions of a return tract. CONCLUSIONS: These observations enlarge and extend our knowledge of the functional repertoire of complex reentrant tracts that occur in infarct-related ventricular tachycardia. The use of common portions of a reentrant tract by several tachycardias is confirmed. Utilization of alternate pathways can account for changes in configuration and cycle length. Spontaneous and induced block can occur at points of entry and exit in a reentrant tract and may identify optimal targets for ablation attempts. Further advances will require greater emphasis on diastolic activation mapping.

Cardiac Pacing, Artificial↗
PubMed1995

Cultured human fibroblasts and not cultured human keratinocytes express a PTH/PTHrP receptor mRNA.

There is increasing evidence that parathyroid hormone (PTH) and PTH-related peptides (PTHrP) are involved in normal skin cell growth; therefore, we investigated whether the PTH/PTHrP receptor was expressed in cultured human keratinocytes and dermal fibroblasts. Northern analyses of poly (A)+ RNA isolated from cultured fibroblasts revealed two PTH/PTHrP receptor transcripts with one major band at 2.5 kb and one minor band at 2.3 kb. These transcripts were consistent with those found in human osteosarcoma cells, which are known to express PTH/PTHrP-R mRNAs. In contrast, after repeated Northern analyses no PTH/PTHrP receptor transcripts were found in poly (A)+ RNA isolated from cultured keratinocytes. Reverse-transcriptase/nested polymerase chain reaction analyses of total RNA isolated from cultured keratinocytes and fibroblasts confirmed the Northern analyses data that the PTH/PTHrP receptor was expressed in cultured fibroblasts but not in cultured keratinocytes. When cultured fibroblasts and keratinocytes were exposed to 10(-7) M PTH (1-34) there was a twofold increase in cAMP levels in the fibroblasts and no demonstrable increase was noted in keratinocytes. These results suggest that skin fibroblasts possess the classical PTH/PTHrP receptor and are target cells for PTH and PTHrP whereas keratinocytes do not have the receptor and are unresponsive to its N-terminal agonist in the stimulation of cAMP formation.

Base Sequence↗
PubMed1995

The antiproliferative and differentiative activities of 1,25-dihydroxyvitamin D3 are potentiated by epidermal growth factor and attenuated by insulin in cultured human keratinocytes.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a potent inhibitor of keratinocyte proliferation, as well as a stimulator of epidermal terminal differentiation. In the present studies, we investigated the influence of epidermal growth factor (EGF) and insulin on the antiproliferative and differentiation activities of 1,25(OH)2D3. Our results indicate the following: (1) EGF caused a dramatic potentiation of the 1,25(OH)2 D3-induced inhibition of 3H-thymidine incorporation into keratinocytes in a dose-dependent manner; (2) insulin acted antagonistically on the EGF-dependent potentiation of the 1,25(OH)2D3-induced antiproliferative activity; (3) transforming growth factor-alpha potentiated 1,25(OH)2D3-induced antiproliferative activity similar to EGF; (4) the EGF effect was not dependent upon 1,25(OH)2D3 receptor mRNA up-regulation; and (5) removal of insulin from medium supplemented with growth factors significantly potentiated the 1,25(OH)2D3-induced inhibition on the number of basal cells and the 1,25(OH)2D3-dependent cornified envelope formation. In conclusion, the antiproliferative activity of 1,25(OH)2D3 in cultured normal human keratinocytes is greatly enhanced by EGF or transforming growth factor-alpha and reduced by insulin. Insulin also inhibits 1,25(OH)2D3-induced terminal differentiation of cultured normal human keratinocytes.

Calcitriol↗
PubMed1995

Acute transverse myelopathy and cutaneous vasculopathy in primary Sjögren's syndrome.

Neurologic complications of primary Sjögren's syndrome (SS) may be under-estimated. Here, we report a patient with primary SS, who developed acute transverse myelopathy (ATM) and skin purpuric lesions simultaneously. In the first episode of myelopathy, the patient's neurologic deficits improved after steroid therapy. However, she died of recurrent myelopathy with systemic complications 4 months later. Review of the English-language literature revealed only 3 cases of primary SS associated with ATM, none of the 3 patients had skin lesions. Anti-Ro(SS-A) antibodies, and ATM in our patient suggests that immune-mediated vasculopathy may play a role in the pathogenesis of acute myelopathy in primary SS.

Acute Disease↗
PubMed1995

Markedly inhibited 7-dehydrocholesterol-delta 7-reductase activity in liver microsomes from Smith-Lemli-Opitz homozygotes.

We investigated the enzyme defect in late cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome, a recessively inherited developmental disorder characterized by facial dysmorphism, mental retardation, and multiple organ congenital anomalies. Reduced plasma and tissue cholesterol with increased 7-dehydrocholesterol concentrations are biochemical features diagnostic of the inherited enzyme defect. Using isotope incorporation assays, we measured the transformation of the precursors, [3 alpha- 3H]lathosterol and [1,2-3H]7-dehydrocholesterol into cholesterol by liver microsomes from seven controls and four Smith-Lemli-Opitz homozygous subjects. The introduction of the double bond in lathosterol at C-5[6] to form 7-dehydrocholesterol that is catalyzed by lathosterol-5-dehydrogenase was equally rapid in controls and homozygotes liver microsomes (120 +/- 8 vs 100 +/- 7 pmol/mg protein per min, P = NS). In distinction, the reduction of the double bond at C-7 [8] in 7-dehydrocholesterol to yield cholesterol catalyzed by 7-dehydrocholesterol-delta 7-reductase was nine times greater in controls than homozygotes microsomes (365 +/- 23 vs 40 +/- 4 pmol/mg protein per min, P < 0.0001). These results demonstrate that the pathway of lathosterol to cholesterol in human liver includes 7-dehydrocholesterol as a key intermediate. In Smith-Lemli-Opitz homozygotes, the transformation of 7-dehydrocholesterol to cholesterol by hepatic microsomes was blocked although 7-dehydrocholesterol was produced abundantly from lathosterol. Thus, lathosterol 5-dehydrogenase is equally active which indicates that homozygotes liver microsomes are viable. Accordingly, microsomal 7-dehydrocholesterol-delta 7-reductase is inherited abnormally in Smith-Lemli-Opitz homozygotes.

Cholesterol↗