Biomedical subjects
Publications and source records attributed to R Yang.
Bone tumor in distal phalanx of finger is rare. Differential diagnosis includes glomus tumor with bone erosion, enchondroma, osteomyelitis, aneurysmal bone cyst and metastasis. We herein present a case with intraosseous epidermoid cyst in distal phalanx which has rarely been reported.
OBJECTIVE: To observe the biliary copper content of nonhepatolenticular degeneration (HLD) controls and changes in the trace elements in the bile, cerebrospinal fluid, blood and urine of hepatolenticular degeneration patients before and after dimercaptosuccinic acid (DMSA) treatment in order to further explore the etiological mechanism of HLD and prove the therapeutic effect of DMSA on HLD patients. METHODS: A consecutive series of 20 patients with HLD were given DMSA orally for 4 weeks. Adult dosage was 1.5 g/day and child dosage 1.0 g/day. Their bile, cerebrospinal fluid, blood and urine samples were obtained before and after treatment with DMSA through duodenal drainage and lumbar puncture. Biliary samples of 22 non-HLD controls were taken by drainage tube after surgical operation. Hitachi-208 atom absorption spectrophotometer was used to assay the content of copper, zinc and iron of each sample. RESULTS: DMSA could effectively improve the symptoms such as dysphasia, salivation, dysphagia and darkening of the skin; limb trembling and myotonia came second; but it showed no obvious effect on dysstasia, limb contracture and deformity, and hepatosplenomegaly. It was effective for the patients who were younger and had no obvious hepatic damage. No serious side effects were seen through the course of treatment. Laboratory study showed that biliary copper content of HLD patients was evidently lower than that of non-HLD controls (P < 0.01); DMSA could evidently improve biliary copper excretion besides clearly increase urinary copper excretion (P < 0.01) and had nothing to do with biliary zinc excretion (P > 0.05). CONCLUSIONS: Biliary copper excretion disturbance participates directly in the pathophysiology of copper retention of HLD patients. DMSA is a favorable cupruretic drug for patients with HLD.
OBJECTIVE: To investigate the allelic heterogeneity of the ATP7B gene in Chinese patients with Wilson's disease (WD). METHODS: Exons of the ATP7B gene from 141 WD patients' DNA were amplified with polymerase chain reaction (PCR) 887-890. Mutations were then screened by single strand conformation polymorphism (SSCP) analysis and further identified by sequencing. RESULTS: The molecular structure of exon 7 of the ATP7B gene from 141 WD patients was analyzed. The same band shift in electrophoretic pattern of 4 cerebral type patients was identified with SSCP and subsequently sequenced. The results showed missense mutation at the second base of the codon as Ser 662 Cys, which is caused by a C to G transversion. CONCLUSIONS: Mutations of the ATP7B gene were investigated for the first time in China and a novel missense mutation was identified in four cases.
OBJECTIVE: To investigate the allelic heterogeneity of ATP 7 B gene in Chinese patients. METHODS: Exons of ATP7B gene from patient's DNA were amplified with PCR technique. Mutations were screened by single strand conformation polymorphism (SSCP) analysis and further confirmed by sequencing. RESULTS: The molecular structure of exon 7 of the ATP7B gene from 141 WD patients was preliminarily analyzed. A similar band shift of 4 encephalopathy type patients was identified with SSCP and sequencing. There was a missense mutation, Ser 662 Cys, which was caused by a C to G transversion at the second base of the codon. CONCLUSIONS: The mutations of Chinese ATP7B gene were investigated for the first time in China and a novel missense mutation was identified.
Bone sialoprotein is a major noncollagenous protein of bone. Parathyroid hormone (PTH) was shown to cause a 2-4-fold increase in the steady-state levels of bone sialoprotein mRNAs within primary cultures of embryonic osteoblasts. The induction could be mimicked by both forskolin and phorbol 12-myristate 13-acetate and was not inhibited by cycloheximide. Transient expression of a approximately 1200-base pair avian 5' bsp promoter/reporter construct demonstrated similar inductions as mRNA levels. Co-transfection of an expression plasmid encoding heat-stable inhibitor of cAMP-dependent protein kinase, a peptide inhibitor of PKA, decreased both the basal and PTH-induced bsp transcription, while co-expression of the catalytic subunit of PKA-induced bsp expression 3-fold. Protein kinase C activation, on the other hand, did not appear to work through its activation of c-fos, since co-transfection of an expression clone for c-fos had no effect. Interestingly, heat-stable inhibitor of cAMP-dependent protein kinase also inhibited the phorbol 12-myristate 13-acetate induction, suggesting that the protein kinase C acts through some form of interaction with the cAMP/PKA pathway. A half-cAMP response element site in the bsp promoter was identified as the cis-acting element that mediated the PTH response by the transient transfections with reporter constructs containing nested deletions of the promoter or a heterologous promoter containing the cAMP response element. In conclusion, these data indicate that PTH stimulation of bsp gene expression is specific to osteoblasts and mediated by changing cellular cAMP/PKA levels. They further suggest that although protein kinase C is capable of stimulating the gene by itself, it plays a minimal role in mediating the PTH induction of bone sialoprotein.
Rapid access to genetic information is central to the revolution taking place in molecular genetics. The simultaneous analysis of the entire human mitochondrial genome is described here. DNA arrays containing up to 135,000 probes complementary to the 16.6-kilobase human mitochondrial genome were generated by light-directed chemical synthesis. A two-color labeling scheme was developed that allows simultaneous comparison of a polymorphic target to a reference DNA or RNA. Complete hybridization patterns were revealed in a matter of minutes. Sequence polymorphisms were detected with single-base resolution and unprecedented efficiency. The methods described are generic and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability.
Atrial natriuretic peptide (ANP) binds to natriuretic peptide receptor-A (NPR-A), a membrane guanylyl cyclase, and to natriuretic peptide receptor-C (NPR-C), which plays a role in peptide clearance. Rat ANP (rANP) mutants that bind rat NPR-A selectively over rat NPR-C were isolated from randomized libraries of rANP-display phage by differential panning. One variant was identified with reduced NPR-C binding; rANP (G16R, A17E, Q18A) [rANP(REA18)]. Synthetic rANP(REA18) was equipotent with rANP in stimulating cGMP production from cloned rat NPR-A (ED50 = 1.8 nM) and was reduced in NPR-C binding by approximately 200-fold. When infused into conscious rats at 0.325 microg/min for 30 min rANP elicited an identical decrease in blood pressure compared with 0.25 microg/min of rANP(REA18), however the natriuretic (P < 0.05) and diuretic (P = 0.07) responses to rANP(REA18) were greater. These data are consistent with a role for NPR-C as a local decoy receptor attenuating NPR-A effects in the kidney, where these receptors are coexpressed. Improved NPR-A specificity could provide more effective natriuretic peptides for treatment of acute renal failure or heart failure.
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The interaction between cyclin-dependent kinase 4 (CDK4) and its inhibitor p16INK4a (p16) was studied by random mutagenesis and yeast two-hybrid system. The gene encoding p16 was mutagenized randomly and the amino acid changes that affect the binding of p16 to CDK4 were identified. Several amino acid residues were shown to be important for the binding and many of these changes occur at residues conserved in all known human p16 family proteins Most of the mutant p16 proteins that failed to bind to CDK4 contained multiple amino acid changes, and these alterations were observed throughout the entire gene with no apparent mutational patterns or hot spots. Some of the mutations that moderately reduced the binding activity severely affected the kinase-inhibitory activity of p16.
The p53 protein directly regulates the expression of the WAF1 (wild-type p53-activated fragment 1) protein which is a cyclin-dependent kinase inhibitor (CDK1). DNA damaging agents such as ionizing or UV radiation, and some chemical agents induce WAF1 in wild-type p53 containing cells, thereby halting cell cycle progression. WAF1 expression is also induced through a p53-independent pathway. Tumor necrosis factor alpha (TNF alpha) is a cytotoxic/cytostatic compound for some human cancer cells. We examined a series of myeloid leukemic cell lines that expressed either no p53 (HL-60, K562) or mutant inactive p53 (KG-1, KCL22,THP-1, U937). The KG-1, HL-60, K562, and KCL22 myeloid leukemic cells increased their levels of WAF1 mRNA in the presence of TNF alpha. We focused on KG-1 cells to determine how TNF alpha modulated WAF1 expression. WAF1 mRNA increased in a dose-dependent manner in the cells after exposure to increasing concentrations of TNF alpha, and this increase occurred in the absence of new protein synthesis. An increase of WAF1 protein and a concominant decrease of cyclin-dependent kinase 2 activity also was found in KG-1 cells. Flow cytometry using 5-bromo-2'-deoxyuridine showed an increase in the proportion of TNF alpha- treated KG-1 cells in the G0/G1 phase of the cell cycle. TNF alpha enhanced the rate of WAF1 transcription only 1.4 fold in TNF alpha-treated KG-1 cells as compared to untreated cells. Notably, however, the half-life (t 1/2) of WAF1 mRNA in TNF alpha-treated cells was 2.5 hours as compared to 0.5 hours in untreated cells. These results indicate that TNF alpha increases WAF1 levels at least in part via a postttranscriptional stabilization of the mRNA; and TNF alpha may mediate its cytostatic effects through WAF1 in some cell types.
Cardiotrophin-1 (CT-1) is a recently discovered cytokine that was isolated based on its ability to induce cardiac myocyte hypertrophy in vitro. In this study, the effects of chronic administration of CT-1 to mice (0.5 or 2 microg by intraperitoneal injection, twice a day for 14 days) were determined. A dose-dependent increase in both the heart weight and ventricular weight to body ratios was observed in the treated groups. The body weights of the animals were unaffected. These results indicate that CT-1 can induce cardiac hypertrophy in vivo. CT-1 was not specific for the heart, however. It stimulated the growth of the liver, kidney, and spleen, and caused atrophy of the thymus. CT-1 administration also increased the platelet counts by 70%, with no change in mean platelet volume. Red blood cell counts were increased in the treated animals, and there was a concomitant increase in haemoglobin concentration. Thus, CT-1 has a broad spectrum of biological activities in vivo. This observation is consistent with previous in-vitro findings showing that the mRNA for CT-1 is expressed in several tissues, and that CT-1 can function through binding to the leukaemia inhibitory factor (LIF) receptor and signalling through the gp130 pathway.
The aim of present study is to assess the pathological changes of gastric coronary vein in cirrhotic patients (n = 30) by immunohistochemical and morphological observation. The damage to endothelium, hypertrophy and hyperplasia of smooth muscle and increament of ECM were found in gastric coronary vein of cirrhotic patients. The vessel wall hardened and thickened with decrease of elasticity. The results showed that the portal hypertension could accompany with portal hypertensive vascular lesions.
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Reports on the prevalence (or incidence) rates of vertebral fracture have been available, but they are limited concerning non-white populations and men of all races. This study used the radiomorphometric method to survey the prevalence rate of vertebral fracture for ethnic Chinese women 40 years and older and Chinese men 65 and older who were randomly selected from four major cities in Taiwan. Three sets of reference values of the height ratios were used for middle-aged women, elderly women, and elderly men. The results showed that in Chinese women, the prevalence rate of vertebral fracture was low before age 50 and showed a steady increase thereafter. In men, the increase was small until age 80. The overall adjusted prevalence rate of vertebral fracture for women older than 65 was 20% and that for men, 12.5% (95% confidence interval 18-22% and 11-14%, respectively.) If only severe deformity was counted [height ratio lower than normal mean minus 4 standard deviations (SD), or Grade II deformity], the adjusted prevalence rate was 15.5% for elderly women and 9.5% for elderly men (95% confidence interval 14-17%, and 8-11%, respectively.) The overall adjusted prevalence rate for women aged 40 and over was 6.8% (95% confidence interval 5.7-8%), or 4.5% (95% confidence interval 3.6-5. 5%) for Grade II lesions. Moreover, for subjects with fracture, elderly women tended to have more fractured vertebrae per person and more Grade II fractures than elderly men. Thus, Chinese women residing in cities of Taiwan had a relatively high prevalence rate of vertebral fracture, a finding compatible with that for United States or European white women, or for Japanese women residing in America. Elderly Chinese men also have a high prevalence rate of vertebral fracture. The age-specific female-to-male ratio of prevalence rate was about 1.5 to 2.3 between age 65 and 80, and close to unity after age 80.
Organ preservation solutions currently used for cold storage of human donor organs are less effective in preserving small intestinal grafts than other organ grafts. The maximal safe period of cold preservation for human small intestinal graft is only about 6 hours. The pathology of preserved and reperfused small intestinal grafts is characterized by mucosal autolysis and sloughing. The authors speculated that the preservation/reperfusion injury results from a proteinase/proteinase-inhibitor imbalance in the graft that favors tissue degradation. This study evaluates whether the addition of an alpha-1-proteinase inhibitor (alpha-1-PI) to the preservation solution can improve graft survival after small bowel transplantation. Forty small intestinal grafts (20 cm long) were harvested from Lewis rats. The grafts were divided randomly into three groups and were preserved in one of the following solutions: normal saline (NS) (n = 10), alpha-1-PI (25 mg/mL; n = 20), or proteinase-free bovine serum albumin (BSA) (25 mg/mL; n = 10). After 12-hour cold storage in the respective solutions, the grafts were transplanted orthotopically into syngeneic recipients. Full-thickness graft biopsies were performed before and 1 hour after revascularization. The effectiveness of preservation was judged by graft histopathology and recipient survival. Histological studies showed that there was less mucosal autolysis and sloughing of the grafts in the alpha-1-Pl group than in the other two groups. All recipients in the NS and BSA groups died of graft failure within 7 days (NS: median, 4 days; range, 2 to 5 days; BSA: median, 6 days; range, 4 to 7). However, 60% (12 of 20) of the recipients in the alpha-1-PI group survived more than 90 days (median, > 90 days; range, 4 to > 90 days; P < .005 v NS or BSA groups, log-rank method). These data suggest that the inclusion of alpha-1-PI in the preservation solution may enhance graft integrity and improve the surgical outcome after small bowel transplantation.
Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high-density oligonucleotide array sequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV-1 clade B proteases was found to be extremely variable and 47.5% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV-1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors.
Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, has therapeutic benefit in animal models of coronary or limb ischemia. However, the hemodynamic effects of VEGF have not been investigated. We examined the effects of VEGF on hemodynamics and cardiac performance. Mean arterial pressure (MAP), heart rate (HR), cardiac output, stroke volume, left ventricular (LV) dP/dt, and hematocrit were measured before and after intravenous injection of VEGF in conscious, instrumented rats. VEGF caused a dose-dependent reduction in MAP and an associated increase in HR. VEGF (250 micrograms/kg) significantly decreased cardiac output and stroke volume without affecting the inotropic state of the left ventricle, as determined by dP/dt. VEGF significantly increased hematocrit. Furthermore, VEGF did not affect contractility or HR in the isolated rat heart in vitro. The data suggest that the VEGF-induced decrease in cardiac output is due to reduced stroke volume, which may be caused by a decrease in venous return rather than a direct effect on myocardial contractility. In addition, pretreatment with N omega-nitro-L-arginine methyl-ester (L-NAME), a nitric oxide (NO) synthase inhibitor, significantly attenuated the depressor and tachycardic responses to VEGF, suggesting that VEGF-induced hypotension may be mediated by NO.