Biomedical subjects

M Fu

Publications and source records attributed to M Fu.

At least 73 records · Page 4Linked to original sources

PubMed2000

Effects of a mandibular repositioner on obstructive sleep apnea.

The purpose of this study was to investigate the effects of a mandibular repositioner on airway, sleep, and respiratory variables in patients with obstructive sleep apnea. Twenty-two patients selected for this study were confirmed with a diagnosis of obstructive sleep apnea based on initial nocturnal polysomnography. The patients were fitted with a mandibular repositioner designed to hold the mandible anteroinferiorly. Six months later, an outcome polysomnographic study was undertaken for each patient with the appliance in place. Lateral cephalometric radiographs in the upright position were also obtained before and after 6 months of treatment. The respiratory disturbance index decreased in 21 of the 22 patients with the appliance in place. The mean respiratory disturbance index of the 22 patients decreased significantly from 40.3 to 11.7 events per hour (P <.01). Some 59.1% of subjects were considered a treatment success with follow-up respiratory disturbance index < 10 events per hour. The mean minimum blood oxygen saturation level during sleep also improved significantly from 73.4% to 81.3% (P <. 01). The mandibular repositioner was constructed to position the mandible at 75% of the maximal mandibular advancement and with a 7 mm opening between the upper and lower incisors, and no aberrant effect on temporomandibular joint was noted. The retropalatal airway space increased and the cross-sectional area of the soft palate and the vertical distance of the hyoid bone to the mandibular plane decreased significantly. The tongue posture became significantly flatter. A significant linear correlation was found between the reduction in apnea index and specific craniofacial skeletal structures (length of anterior cranial base, mandibular plane angle, and upper to lower facial height ratios, P <.05). Subjects with a smaller reduction in apnea index tended to have shorter anterior cranial bases, steeper mandibular planes, and smaller upper to lower facial height ratios. We conclude that a mandibular repositioner may be an effective treatment alternative for obstructive sleep apnea and that a reduction in the frequency of apneic episodes is mainly attributed to the effects of the appliance on oropharyngeal structures.

Adult↗

PubMed2000

A monoclonal antibody directed against an autoimmune epitope on the human beta1-adrenergic receptor recognized in idiopathic dilated cardiomyopathy.

A monoclonal antibody (MAb M16) was obtained by immunizing Balb/C mice with free peptide H26R, corresponding to the second extracellular loop of the human beta1-adrenergic receptor (beta1AR), against which functional autoantibodies have been detected in patients with idiopathic dilated cardiomyopathy. The MAb was found to be of IgG2b type and directed against a conformational epitope, encompassing the sequence recognized by the human autoantibodies. BIAcore measurements yielded an equilibrium constant of 6.5 X 10(7) M1 with an association rate constant (kon) of 6.5 X 10(4) M(-1) sec(-1) and a dissociation rate constant (koff) of 1.0 X 10(-3) sec(-1). It immunoprecipitated only poorly the solubilized beta1AR of Sf9 cell membranes. Functionally, the MAb was capable of not only reducing the number of the maximal binding sites to the beta1-adrenergic receptor of transfected Sf9 cell membranes, but also of displaying a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These properties, which the MAb shares with the human autoantibodies, makes it an interesting tool for passive transfer studies in mice.

Amino Acid Sequence↗

PubMed2000

Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice.

The ability to regulate temporal- and spatial-specific expression of target genes in transgenic mice will facilitate analysis of gene function and enable the generation of murine models of human diseases. The genetic analysis of mammary gland tumorigenesis requires the development of mammary gland-specific transgenics, which are tightly regulated throughout the adult mammary epithelium. Analysis of genes implicated in mammary gland tumorigenesis has been hampered by mosaic transgene expression and the findings that homozygous deletion of several candidate genes (cyclin D1, Stat5A, prolactin receptor) abrogates normal mammary gland development. We describe the development of transgenic mouse lines in which sustained transgene expression was inducibly regulated, both specifically and homogeneously, in the adult mammary gland epithelium. Transgenes encoding RXRalpha and a chimeric ecdysone receptor under control of a modified MMTV-LTR, which targets mammary gland expression, were used. These transgenic 'receptor' lines were crossed with transgenic 'enhancer' lines in which the ecdysone/RXR binding site induced ligand-dependent expression of transgenic beta-galactosidase. Pharmacokinetic analysis of a highly bioactive ligand (ponasterone A), identified through screening ecdysteroids from local plants, demonstrated sustained release and transgene expression in vivo. This transgenic model with both tightly regulated and homogeneous transgene expression, which was sustained in vivo using ligands readily extracted from local flora, has broad practical applicability for genetic analysis of mammary gland disease.

Animals↗

PubMed2000

Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against beta1-adrenoceptor.

We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1-peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor.

Amino Acid Sequence↗

PubMed2000

Cyclooxygenase 2 (COX-2) gene activation is regulated by cyclic adenosine monophosphate.

Prostaglandin E2 production by tissue-fixed macrophages (Mphi) after severe injury contributes to an enhanced susceptibility to infection and sepsis. The purpose of this study was to investigate the effect of cyclic adenosine monophosphate (cAMP) on prostaglandin (PGE2) production and cyclooxygenase II (COX-2) gene activation in LPS-stimulated macrophages (Mphi). RAW264.7 cells, a mouse Mphi cell line, were exposed to various concentrations of dibutyryl cAMP +/- lipopolysaccharide (10 microg/mL) stimulation. Total Mphi ribonucleic acid (RNA) was harvested for the determination of COX-2 messenger RNA (mRNA) with mouse complementary deoxyribonucleic acid (cDNA) by Northern blot assay. Mphi supernatant was collected for the measurement of tumor necrosis factor (TNF) by L929 bioassay and PGE2 by enzyme-linked immunosorbent assay (ELISA), respectively. Mphi NFkappaB activity was determined by electrophoretic mobility shift assays (EMSA). Dibutyryl cAMP significantly inhibited TNF production by LPS-stimulated Mphi. Dibutyryl cAMP (1 mM) alone induced PGE2 production. Dibutyryl cAMP (100 microM and 1 mM) also augmented PGE2 production by LPS-stimulated Mphi. Dibutyryl cAMP had similar effect on Mphi COX-2 mRNA expression and NFkappaB activity. Our data demonstrate that cAMP modulates Mphi TNF production and upregulates COX-2 gene and PGE2 production.

Animals↗

PubMed2000

Unexpected loss of bipolar pacing with implanted dual chamber pacemakers.

Bipolar leads are most commonly used in the current practice of pacemaker therapy. In our study of 124 patients implanted with Guidant/Cardiac Pacemakers (CPI) Vigor dual chamber pacemakers, 5 patients had unexpectedly abrupt increases in bipolar lead impedance and pacing threshold 2 weeks to 18 months postimplantation without changes in sensing function. With the lead configuration reprogrammed to unipolar, the lead impedance and pacing threshold were restored to appropriate ranges. The changes in bipolar lead parameters can be caused by the CPI's "Quick Connect" (QC1) header lead system incorporated in these pacemakers.

Aged↗

PubMed2000

Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway.

The neu (c-erbB-2) proto-oncogene encodes a tyrosine kinase receptor that is overexpressed in 20 to 30% of human breast tumors. Herein, cyclin D1 protein levels were increased in mammary tumors induced by overexpression of wild-type Neu or activating mutants of Neu in transgenic mice and in MCF7 cells overexpressing transforming Neu. Analyses of 12 Neu mutants in MCF7 cells indicated important roles for specific C-terminal autophosphorylation sites and the extracellular domain in cyclin D1 promoter activation. Induction of cyclin D1 by NeuT involved Ras, Rac, Rho, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, but not phosphatidylinositol 3-kinase. NeuT induction of the cyclin D1 promoter required the E2F and Sp1 DNA binding sites and was inhibited by dominant negative E2F-1 or DP-1. Neu-induced transformation was inhibited by a cyclin D1 antisense or dominant negative E2F-1 construct in Rat-1 cells. Growth of NeuT-transformed mammary adenocarcinoma cells in nude mice was blocked by the cyclin D1 antisense construct. These results demonstrate that E2F-1 mediates a Neu-signaling cascade to cyclin D1 and identify cyclin D1 as a critical downstream target of neu-induced transformation.

Animals↗

PubMed2000

Ral GTPases contribute to regulation of cyclin D1 through activation of NF-kappaB.

Ral GTPases have been implicated as mediators of Ras-induced signal transduction from observations that Ral-specific guanine nucleotide exchange factors associate with Ras and are activated by Ras. The cellular role of Ral family proteins is unclear, as is the contribution that Ral may make to Ras-dependent signaling. Here we show that expression of activated Ral in quiescent rodent fibroblasts is sufficient to induce activation of NF-kappaB-dependent gene expression and cyclin D1 transcription, two key convergence points for mitogenic and survival signaling. The regulation of cyclin D1 transcription by Ral is dependent on NF-kappaB activation and is mediated through an NF-kappaB binding site in the cyclin D1 promoter. Ral activation of these responses is likely through an as yet uncharacterized effector pathway, as we find activation of NF-kappaB and the cyclin D1 promoter by Ral is independent of association of Ral with active phospholipase D1 or Ral-binding protein 1, two proteins proposed to mediate Ral function in cells.

3T3 Cells↗

PubMed2000

Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle.

Although the beta(1)-adrenergic agent dobutamine is used clinically to provide inotropic support to the failing myocardium, it could jeopardize the myocardium by depleting energy reserves. This investigation delineated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular (RV) myocardium. The right coronary artery (RCA) of anesthetized dogs was cannulated for controlled perfusion with arterial blood, and regional RV contractile function was measured. RCA perfusion pressure was lowered from 100 mmHg baseline to 40 mmHg, and flow fell by 54%. At 15-min hypoperfusion, dobutamine was infused into the RCA at either 0.01 (low-dose dobutamine) or 0.06 microgram. kg(-1). min(-1) (high-dose dobutamine) for 15 min. Regional power (systolic segment shortening x isometric developed force x heart rate) stabilized at 63% of baseline during hypoperfusion. Low-dose dobutamine restored power to baseline but did not increase RV myocardial O(2) consumption (MVO(2)) and thus increased myocardial O(2) utilization efficiency (O(2)UE:power/MVO(2)). At 5 min, high-dose dobutamine enhancement of power was similar to that of low-dose dobutamine, but by 15 min, power and O(2)UE fell to untreated levels. Remarkably, low-dose dobutamine tripled cytosolic phosphorylation potential; in contrast, high-dose dobutamine lowered phosphorylation potential to 45% of the untreated value. Analyses of glucose uptake and glycolytic intermediates revealed sustained enhancement of glycolysis by low-dose dobutamine, but glycolysis became limited at glyceraldehyde 3-phosphate dehydrogenase during high-dose dobutamine treatment. In summary, low-dose dobutamine improved mechanical performance and efficiency of the hypoperfused RV myocardium while increasing myocardial energy reserves, but high-dose dobutamine failed to sustain improved function and depleted energy reserves. Dobutamine is capable of improving both contractile function and cellular energetics in the hypoperfused RV myocardium, but dosage should be carefully selected.

Animals↗

PubMed2000

Growth hormone improves bioenergetics and decreases catecholamines in postinfarct rat hearts.

The aims of this study were to examine, in vivo, the effects of GH treatment on myocardial energy metabolism, function, morphology, and neurohormonal status in rats during the early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague Dawley rats. Three different groups were studied: MI rats treated with saline (n = 7), MI rats treated with GH (MI + GH; n = 11; 3 mg/kg x day), and sham-operated rats (sham; n = 8). All rats were investigated with 31P magnetic resonance spectroscopy and echocardiography at 3 days after MI and 3 weeks later. After 3 weeks treatment with GH, the phosphocreatine/ATP ratio increased significantly, compared with the control group (MI = 1.69 +/- 0.09 vs. MI + GH = 2.42 +/- 0.05, P < 0.001; sham = 2.34 +/- 0.08). Treatment with GH significantly attenuated an increase in left ventricular end systolic volume and end diastolic volume. A decrease in ejection fraction was prevented in GH-treated rats (P < 0.05 vs. MI). Myocardial and plasma noradrenaline levels were significantly lower in MI rats treated with GH. These effects were accompanied by normalization of plasma brain natriuretic peptide levels (sham = 124.1 +/- 8.4; MI = 203.9 +/- 34.7; MI + GH = 118.3 +/- 8.4 ng/ml; P < 0.05 vs. MI). In conclusion, GH improves myocardial energy reserve, preserves left ventricular function, and attenuates pathologic postinfarct remodeling in the absence of induction of left ventricular hypertrophy in postinfarct rats. The marked decrease in myocardial content of noradrenaline, after GH treatment, may protect myocardium from adverse effects of catecholamines during postinfarct remodeling.

Animals↗

PubMed2000

Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy.

Growing evidence suggests that autoimmune mechanisms play an important role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The aim of the study was to evaluate the effects of transfer of lymphocytes from patients with DCM into severe combined immunodeficiency (SCID) mice on the heart structure and function. Thirty CB-17 SCID (6-8 weeks old) mice were used and divided into 3 groups (n = 10). Mice were injected intraperitoneally with up to 25 x 10(6) peripheral blood lymphocytes (PBL) from either patients with DCM which contain human autoantibodies against cardiac beta1-adrenergic receptors and M2-muscarinic receptors (DCM group) or PBL from healthy controls (control-H group). Ten mice did not receive any injections and were used as baseline controls (control-N group). Echocardiography and morphological studies were performed seventy five days after the transfer. Results showed that in DCM group, left ventricle dimensions (LVD) in diastole were increased (4.2 +/- 0.1mm) as compared to both control-H group (3.8 +/- 0.1mm) and control-N group (3.6 +/- 0.1 mm) (p < 0.01). Further, there was a trend for increased LVD in systole. Fractional shortening was not different between groups. Histological evaluation revealed accumulation of human lymphocytes in the capillaries and scarce infiltration of the lymphocytes in the hearts from DCM group. Diffuse fibrosis was significant increased in DCM mice as compared to mice receiving PBL from normal subjects (2.2 +/- 0.3% vs. 0.8 +/- 0.1%, p < 0.01). In conclusion, transfer of the PBL from the patients with DCM was able to induce early stage of heart dilatation in SCID mice. These data provide for the first time the direct evidence supporting that the autoimmune mechanism is important in the pathogenesis of human DCM.

Animals↗

PubMed2000

The effects of recombinant RA538 and antisense c-myc adenovirus on tumor cells and the molecular mechanism concerned.

OBJECTIVE: Compare the biological effects of recombinant RA538 and antisense c-myc adenovirus on human gastric cancer cell line (SGC7901) and explore the molecular mechanism in vitro and in vivo. METHODS: SGC7901 cells were treated with Ad-RA538, Ad-AS c-myc or Ad-LacZ. MTT, DNA ladder, TUNEL and FCM, RT-PCR, Western blot analysis, the tumorigenicity in nude mice and experimental therapy of the nude mice were used. RESULTS: Ad-RA538 and Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis of SGC7901 cells. The growth of the Ad-RA538- and Ad-ASc-myc-infected SGC7901 cells were inhibited by 76.3% and 44.1% respectively. The over expression of RA538 and ASc-myc could down-regulate expression of c-myc, bcl-2 and cyclinD1 gene and up-regulate expression of bax gene, but it could not regulate expression of p53, p16, TGase, and ras gene. The tumorigenicity of Ad-RA538 or Ad-ASc-myc in nude mice showed that three of three mice failed to form tumor, compared with Ad-LacZ and parent SGC7901 cells from 7 to 30 days. Experimental therapy of the nude mice bearing subcutaneous tumor of SGC7901 cells showed that intratumor instillation of Ad-RA538 and Ad-ASc-myc inhibited the growth of the tumors. Ad-RA538- and Ad-ASc-myc-treated tumors were inhibited by 60.7% or 68.9% respectively, compared with the tumor injected with Ad-LacZ and mock. CONCLUSION: The expression of Ad-RA538 and Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cell in vitro and in vivo. RA538 and ASc-myc relate to c-myc, bcl-2, cyclinD1 and bax gene closely and have noticeable biologic effects on gastric cancer cells.

Adenoviridae↗

PubMed2000

Direct angioplasty of totally occluded left main coronary artery in acute myocardial infarction complicated by cardiogenic shock: report of two cases and literature review.

Acute total occlusion of the left main coronary artery is usually characterized by a rapid course of deterioration that challenges therapeutic intervention. Unlike subtotal occlusion of the left main coronary artery, acute total occlusion of the left main coronary artery is extremely rare and has a grave prognosis. Most patients with this problem die suddenly or go into cardiogenic shock. Direct percutaneous transluminal coronary angioplasty (PTCA) was performed on 2 patients, both suffering from cardiogenic shock due to acute total occlusion of the left main coronary artery. Both patients underwent coronary artery bypass surgery subsequently. One patient, who had substantial intercoronary collaterals, remained asymptomatic at 31 months of follow-up. The other, who had no intercoronary collateral circulation, expired 3 days after coronary artery bypass surgery. We conclude that direct PTCA to the acutely occluded unprotected left main coronary artery in cardiogenic shock patients is a potentially life-saving procedure, and the presence or absence of collaterals from the dominant right coronary artery will influence the clinical outcome.

Angioplasty, Balloon, Coronary↗

PubMed2000

Extensive dissection to the right sinus of Valsalva in coronary angioplasty: case report.

Percutaneous transluminal coronary angioplasty was first introduced in 1977 by Gruentzig and now provides the option of nonsurgical revascularization for up to 1/2 of patients who undergo diagnostic catheterization for coronary artery disease. Today, although there have been great improvements in technology and operator experience, complications still occur during coronary angiography and revascularization. Coronary dissection, one of the most frequently occurring complications during angiography and angioplasty, occurs in various forms. However, right coronary dissection and retrograde extension to the aortic sinus of Valsalva is extremely unusual during an interventional procedure. We report such an unusual complication which occurred during balloon angioplasty and which was successfully managed by coronary stenting. This unusual complication may have potential risk of quickly involving the entire aorta, causing acute severe aortic regurgitation, acute myocardial infarction, requiring emergency surgery, and even resulting in death. Therefore, prompt diagnosis and management of this complication are very important.

Angioplasty, Balloon, Coronary↗

PubMed2000

Ischaemic myelopathy presenting as Guillain-Barré syndrome.

Spinal cord stroke is uncommon. We report a woman presenting with paraesthesia followed by tetraparesis and respiratory failure who was initially diagnosed as having Guillain-Barré syndrome. Subsequent clinical and imaging features supported the diagnosis of an anterior spinal cord infarction. We describe the main clinical and imaging features of this condition.

Adult↗

PubMed2000

Rationale for directional atherectomy and adjunctive stenting in a patient with non-Q wave myocardial infarction.

The development of percutaneous transluminal balloon angioplasty (PTCA) is the greatest revolution in the management of stenotic coronary artery disease. However, PTCA is limited in its application to some specific subgroups of complex lesions such as bifurcational, ostial and plaque burden lesions. For this reason, some new strategies including directional atherectomy (DCA) have been developed as advanced modalities in the treatment of these complex lesions, which if treated by PTCA would certainly yield poor outcomes. We report a case of non-Q wave myocardial infarction resulting from obstruction of the ostium of left anterior descending artery. DCA and adjunctive stenting to the lesion were successfully performed and the patient was discharged uneventfully after the procedure. We suggest that DCA is a striking method and has much merit in the treatment of complex lesions with a high rate of success. In view of consideration of restenosis remains an importantly unresolved problem in percutaneous coronary intervention in specific subgroups of complex lesions. In the future, adequate debulking by mean of DCA in combination with adjunctive stenting which recently emerges as a promising treatment in the prevention of restenosis may provide a more consistent and attractive method for prevention of restenosis in these complex lesions.

Aged↗

PubMed2000

The practice of evidence-based medicine in an acute medical ward: retrospective study.

OBJECTIVE: To review the practice of evidence-based medicine with respect to drug treatment given to medical in-patients. DESIGN: Retrospective study. SETTING: Teaching hospital, Hong Kong. PATIENTS: Medical records of 129 consecutive patients who were admitted to the acute adult general medical ward from 1 September 1998 to 30 September 1998 were reviewed. MAIN OUTCOME MEASURES: Primary diagnoses, drug treatments prescribed, and the level of evidence (based on a literature search of randomised controlled trials and relevant studies) that supported the treatment given. RESULTS: For the 129 patients studied, 91 drug interventions had been prescribed on 312 occasions. Treatment that was supported by randomised controlled trials was prescribed in 162 (52.9%) cases. In 121 (38.8%) cases, patients were given standard and commonly used drugs that were not supported by evidence from clinical trials, and in 29 (9.3%) cases, the treatments given had no substantial supporting evidence. The management of some frequently encountered medical conditions was not based on trial data, because the relevant studies had not been conducted. CONCLUSION: Basing treatment on comparative efficacy results is a worthwhile goal, but there are limitations in conducting literature searches to identify relevant trials and studies. Evidence-based medical practice is not applicable in a large number of commonly encountered conditions.

Adult↗

PubMed2000

Three-dimensional echocardiographic image of atrial septal aneurysm: report of two cases.

Atrial septal aneurysm (ASA) is a rare congenital anomaly. It may occur as an isolated pathology or in association with other cardiovascular lesions such as mitral valve disease, atrial septal defect, and others. The diagnosis of ASA became more widely recognized with the use of 2-dimensional echocardiography. Three-dimensional echocardiography is a recently developed imaging technique. It can be used as an adjunct to conventional transesophageal echocardiography. Images of different aspects of cardiac chambers and valves can be obtained with 3-dimensional echocardiography. This paper reports on 2 cases of different types of ASA imaged by 3-dimensional echocardiography. The images were obtained from the left and right atriums, respectively. The 3-dimensional image taken from the left atrium showed the ASA to be a localized concave structure, and the 3-dimensional image taken from the right atrium showed the ASA to be a localized bulging structure. Our pictures are the first reported 3-dimensional echocardiographic images of ASA. We hope this report will allow for a more comprehensive understanding of its pathology.

Aged↗