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Biomedical subjects

M Ho

Publications and source records attributed to M Ho.

At least 55 records · Page 3Linked to original sources
PubMed2000

Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelial cells under flow.

Plasmodium falciparum-infected erythrocytes (IRBCs) have been shown to interact with a number of endothelial adhesion molecules expressed on transfectants, on cell lines, and as immobilized purified receptor proteins under flow conditions. However, the experiments were designed in such a way that maximal numbers of adhesion molecules were provided as substratum. Whether the interactive events actually occur on microvascular endothelium, where the distribution and expression of adhesion molecules may be less, remains undetermined. In this study, the cytoadherance of IRBCs on human dermal microvascular endothelial cells (HDMECs) as a model of human microvasculature was examined. IRBCs were observed to tether, roll, and adhere on resting HDMECs, which constitutively expressed CD36 and intercellular adhesion molecule-1 (ICAM-1) at an optimal shear stress of 1 dyne/cm(2). Stimulation of HDMECs with tumor necrosis factor-alpha for 5 and 24 hours, which resulted in up-regulation of ICAM-1 and induction of vascular cell adhesion molecule-1 expression, significantly increased the percentage of rolling cells that adhered without affecting the rolling flux. In contrast, P-selectin expression on HDMECs induced by oncostatin M led to an increase in both rolling flux and adhesion. Inhibition studies with receptor-specific monoclonal antibodies revealed that adhesion of IRBCs on HDMECs was largely CD36 dependent, whereas rolling could be mediated by any of the adhesion molecules studied. Collectively, these findings indicate that IRBCs interact synergistically with multiple adhesion molecules on vascular endothelium. The rolling of IRBCs may be the rate-limiting step in cytoadherance, since it can be modulated by cytokines to enhance CD36-mediated IRBC adhesion.

Animals↗
PubMed2000

Dopamine uptake by mouse neuroblastoma N1E-115 cells stably expressing human dopamine transporter is differentially inhibited by anti-idiotypic ab2beta antibodies mimicking the configuration of cocaine.

We have successfully constructed a mouse neuronal N1E-115 cell line stably expressing a fully functional human dopamine transporter (hDAT). Previous studies in our laboratory have produced several anti-idiotypic Ab2beta antibodies that mimic the configuration of the cocaine molecule at their antigen-combining site. In the present study, we observed that some anti-idiotypic Ab2beta antibodies inhibited dopamine uptake by the hDAT-transfected line. Each antibody showed a different level of inhibition (between 40% and 90%). These findings suggest that the internal images of these antibodies can be used as analog peptides that may compete with cocaine for its binding site on the transporter but not impair dopamine uptake as much as cocaine does.

Animals↗
PubMed2000

A 5-year study of the seroepidemiology of Klebsiella pneumoniae: high prevalence of capsular serotype K1 in Taiwan and implication for vaccine efficacy.

Seroepidemiology of Klebsiella pneumoniae was determined for 1000 nonrepetitive K. pneumoniae isolates collected by a medical center in Taiwan during 1993-1997. Of these, 630 isolates (63%) were from community-acquired infections; the rest were from hospital-acquired infections. The isolates were serotyped according to capsular antigen by countercurrent immunoelectrophoresis. About 77% were typeable. Serotypes K1 and K2 accounted for 21.7% and 9.3% of the isolates, respectively, followed by K57 (5.1%), K54 (4.2%), K21 (3. 3%), and K16 (3%). The frequency of serotype K1 among bacteremic isolates (30.8%) far exceeded that reported by other investigators worldwide. Molecular typing of random K1 isolates by pulsed-field gel electrophoresis revealed several different pulsotypes, suggesting a nonclonal spread. This study indicates that a Klebsiella vaccine developed in Europe is not optimal for use in Taiwan because it does not contain the most predominant serotypes-K1, K54, and K57.

Antibodies, Bacterial↗
PubMed2000

Risk factors for acquired myasthenia gravis in cats: 105 cases (1986-1998).

OBJECTIVE: To determine prevalence of initial clinical signs and risk factors for acquired myasthenia gravis (MG) in cats. DESIGN: Retrospective case-control study. ANIMALS: 105 cats from the United States, Canada; and the United Kingdom with a confirmed diagnosis of acquired MG and 510 cats with other neuromuscular disorders, including generalized weakness, megaesophagus, and dysphagia (control group). PROCEDURES: Records were retrieved from a data-base containing results of serum samples tested for acetylcholine receptor antibodies. Signalment, including breed, age, and state or country of origin, month of onset, and initial clinical signs were obtained. An acetylcholine receptor antibody titer > 0.3 nmol/L was diagnostic for acquired MG. Unconditional logistic regression was used for statistical analysis. RESULTS: Compared with mixed-breed cats, the breed with the highest relative risk of acquired MG was the Abyssinian (including Somali). Significant differences between sexes were not detected. There was no compelling evidence for a difference in risk of developing MG between states or countries. Relative risk increased after 3 years of age. The most common clinical signs were generalized weakness without megaesophagus and weakness associated with a cranial mediastinal mass. Focal signs, including megaesophagus and dysphagia without signs of generalized weakness, were also evident. CONCLUSIONS AND CLINICAL RELEVANCE: A breed predisposition for acquired MG in Abyssinians (and related Somalis) was observed. Clinical signs were variable and included generalized weakness, megaesophagus, and dysphagia. A cranial mediastinal mass was commonly associated with MG in cats.

Age Factors↗
PubMed2000

Physiological functions of protein kinase inhibitors.

Protein kinases are key regulatory enzymes involved in a multitude of biochemical pathways. This chapter will describe the current research on targeting specific protein kinases with inhibitors in attempts to disrupt flux through specific pathways. Targeting specific kinases presents a distinct challenge as there are hundreds of individual kinase enzymes that use ATP as a substrate to phosphorylate specific target molecules. The challenge clearly lies in obtaining specificity for a given kinase, thus allowing inhibition or activation of a specific pathway. This chapter will focus on two areas of kinase inhibitors, those that target the MAP kinase pathway and those directed against the phosphatidylinositol-3 kinase (PI-3K) related kinase family. The cellular and physiological effects of inhibition of the various pathways controlled by these kinases will be reviewed.

Androstadienes↗
PubMed2000

The mouse Kell blood group gene (Kel): cDNA sequence, genomic organization, expression, and enzymatic function.

The human Kell blood group system is important in transfusion medicine, since Kell is a polymorphic protein and some of its antigens can cause severe reactions if mismatched blood is transfused, while maternal alloimmunization may lead to fetal and neonatal anemia. In humans, Kell is an Mr 93,000 type II membrane glycoprotein with endothelin-3-converting enzyme activity that is linked by a single disulfide bond to another protein, XK, that spans the membrane ten times. An absence of XK leads to clinical symptoms termed the McLeod syndrome. We determined the cDNA sequence of the mouse Kell homologue, the organization of the gene, expression of the protein and its enzymatic function on red cells. Comparison of human and mouse Kell cDNA showed 80% nucleotide and 74% amino acid sequence identity. Notable differences are that the mouse Kell protein has eight probable N-linked carbohydrate side chains, compared to five for human Kell, and that the mouse homologue has one more extracellular cysteine than human Kell protein. The mouse Kell gene (Kel), like its human counterpart, is similarly organized into 19 exons. Kel was located to proximal Chromosome 6. Northern blot analysis showed high expression in spleen and weaker levels in testis and heart. Western blot analysis of red cell membrane proteins demonstrated that mouse Kell glycoprotein has an apparent Mr of 110,000 and, on removal of N-linked sugars, 80,000. As in human red cells, Kell is disulfide-linked to XK and mouse red cells have endothelin-3-converting enzyme activity.

Amino Acid Sequence↗
PubMed2000

Effect of adult microsurgical varicocelectomy on testicular volume.

OBJECTIVES: To re-examine the potential influence of varicocelectomy on testicular volume using scrotal ultrasonography, because it has been reported that total testicular volume (assessed by physical examination) increases after adult varicocele ligation. METHODS: A retrospective review of the testicular volume and semen parameters of 61 men who underwent microsurgical varicocelectomy between 1996 and 1998 was performed. Ultrasound-derived testicular volumes and total motile sperm counts were compared before varicocelectomy and at a mean of 7.2 months postoperatively. RESULTS: Bilateral varicocelectomy was performed in 22 men; 39 men underwent a left-sided procedure only. Overall, no significant change was found in the mean total testicular volume after varicocelectomy compared with preoperatively (24.0 versus 23.9 mL, respectively; P = 0.74). Similarly, the testicular volumes did not change significantly after left or bilateral varicocelectomy (P >0.05). Overall, the mean total motile sperm count increased significantly after varicocelectomy (17. 9 to 25.4, P = 0.05). CONCLUSIONS: This was the first study to examine the effect of adult varicocelectomy on testicular volume using ultrasound-derived measurements of volume. Unlike previous findings, our data suggest that although adult varicocelectomy improves semen quality in most infertile men, it does not result in a significant increase in testicular volume.

Adult↗
PubMed2000

Predictors of adverse events with intramuscular ketamine sedation in children.

STUDY OBJECTIVE: Ketamine is a safe and effective sedative for emergency department procedures in children. However, the use of ketamine sometimes is associated with airway complications, emesis, and recovery agitation. We wished to identify predictors of these adverse events that clinicians might use to risk-stratify children who are candidates for ketamine sedation. METHODS: We analyzed data from 1,021 ED intramuscular ketamine sedations in children 15 years of age or younger at a university medical center and an affiliated county hospital over a 9-year period. Five potential predictor variables (age, gender, American Society of Anesthesiologists' [ASA] risk classification, quantity of first ketamine dose, and number of ketamine doses administered) were compared between children with and without complications. We used multiple logistic regression analyses to determine the association of these 5 variables with emesis and recovery agitation, and validated these analyses with bootstrap resampling techniques. We compared children with and without airway complications using univariate statistics alone, as there were too few patients with airway complications to support a multivariate analysis. RESULTS: No study variables had significant univariate associations with airway complications (all P values >.40). We found emesis to be associated with increasing age in multivariate analysis (odds ratio [OR] 1.25 per year, bias-corrected 95% confidence interval [CI] 1.17 to 1.34, P<.001). The incidence of emesis was 12. 1% in children aged 5 years or older, and 3.5% in those younger than 5 years (Delta8.6%, 95% CI 4.9% to 12.1%). Recovery agitation was associated with the presence of an underlying medical condition (ie, ASA class > or =2, OR 3.05, bias-corrected 95% CI 1.65 to 7.30, P=.004) and inversely associated with increasing age (OR 0.79 per year, bias-corrected 95% CI 0.69 to 0.89, P<.001). The incidence of recovery agitation was 17.9% in ASA class 1 children and 33.3% in children in ASA class 2 or greater (Delta-15.4%, 95% CI 0.0% to -30. 7%). The incidence of recovery agitation was 12.1% in children aged 5 years or older, and 22.5% in those younger than 5 years (Delta-10. 4%, 95% CI -3.0% to -17.7%). Bootstrap resampling techniques validated the importance of the significant variables identified in the regression analyses. CONCLUSION: No study variable was predictive of ketamine-associated airway complications. Emesis that occurred after ketamine administration was modestly associated with increasing age. Recovery agitation was modestly associated with decreasing age and the presence of an underlying medical condition. The discriminatory power of these variables was low enough as to be unlikely to alter clinical decisions regarding patient selection for ketamine administration. No evidence of a significant ketamine dose relationship was noted for airway complications, emesis, or recovery agitation.

Adolescent↗
PubMed2000

Comparison of screening methods for detection of extended-spectrum beta-lactamases and their prevalence among Escherichia coli and Klebsiella species in Hong Kong.

Three tests, the disk diffusion test, the double-disc synergy test and the inhibitor-potentiated disc diffusion test, were compared for their abilities to detect production of extended-spectrum beta-lactamases (ESBL) in 702 Escherichia coli and 472 Klebsiella spp. strains from four hospitals. Eleven percent E. coli and 13% Klebsiella spp. were found to produce ESBL. As an indicator of ESBL activity, the sensitivities of the five extended-spectrum beta-lactams were as follows: cefotaxime (100%), cefpodoxime (99.3%), ceftriaxone (98.6%), aztreonam (93%) and ceftazidime (57.7%) when interpreted using the National Committee for Clinical Laboratory Standards criteria. Their positive predictive values ranged from 67.8-83.8%. Both the inhibitor-potentiated disc diffusion test and the double-disc synergy test (at three inter-disc widths of 20, 25 and 30 mm) were capable of identifying all the ESBL-producers. However, at a single inter-disc width of 30 mm, the double-disc synergy test has limited sensitivity (83.8%). As a second test for confirming ESBL activity in strains with reduced susceptibility to beta-lactams, the inhibitor-potentiated disc diffusion test is therefore a simple and reliable option.

Escherichia coli↗
PubMed2000

[(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors.

Binding of the 5-HT(7) receptor antagonist radioligand [(3)H]-SB-269970 to human 5-HT(7(a)) receptors expressed in HEK293 cell membranes (h5-HT(7(a))/293) and to guinea-pig cerebral cortex membranes, was characterized and compared with [(3)H]-5-CT binding. [(3)H]-SB-269970 (1 nM) showed full association with h5-HT(7(a))/293 membranes after 40 min. Specific binding at equilibrium represented >90% of total binding and was fully reversible by methiothepin (10 microM), full dissociation occurring by 100 min. The association (k(+1)) and dissociation (k(-1)) rate constants were 0.05 nM(-1)min(-1) and 0.05 min(-1) respectively, giving a K(D) (k(-1)/k(+1)) of 1.0 nM. [(3)H]-SB-269970 bound saturably and apparently monophasically to both h5-HT(7(a))/293 and guinea-pig cortex membranes, with K(D) values of 1.25+/-0.05 and 1.7+/-0.3 nM respectively. The B(max) for [(3)H]-SB-269970 to both h5-HT(7(a))/293 and guinea-pig cortex membranes (5780+/-380 and 125+/-8.2 fmoles mg protein(-1) respectively) was similar to that for [(3)H]-5-CT (6190+/-940 and 143+/-19 fmoles mg protein(-1) respectively). These data suggest that, in each tissue, both radioligands labelled the same population of receptors, which appear to be present in an agonist high affinity state. The profile of compound inhibition of [(3)H]-SB-269970 binding to h5-HT(7(a))/293 and guineapig cortex membranes correlated well (corr. coeff. 0.98) with those for [(3)H]-5-CT binding and were consistent with the profiles reported previously for the human 5-HT(7(a)) and guinea-pig cortex 5-HT(7) receptors using [(3)H]-5-CT. Hill slopes for inhibition of [(3)H]-SB-269970 and [(3)H]-5-CT binding were close to 1, consistent with binding to a single receptor population in both tissues. [(3)H]-SB-269970 represents the first selective 5-HT(7) antagonist radioligand, which should aid further characterization of 5-HT(7) receptors in recombinant and native tissues and help establish their role in brain function.

Animals↗
PubMed2000

5-HT(1A) receptor agonist-antagonist binding affinity difference as a measure of intrinsic activity in recombinant and native tissue systems.

1. It has been reported that radiolabelled agonist : antagonist binding affinity ratios can predict functional efficacy at several different receptors. This study investigates whether this prediction is true for recombinant and native tissue 5-HT(1A) receptors. 2. Saturation studies using [(3)H]-8-OH-DPAT and [(3)H]-MPPF revealed a single, high affinity site (K(D)approximately 1 nM) in HEK293 cells expressing human 5-HT(1A) receptors and rat cortex. In recombinant cells, [(3)H]-MPPF labelled 3 - 4 fold more sites than [(3)H]-8-OH-DPAT suggesting the presence of more than one affinity state of the receptor. [(3)H]-Spiperone labelled a single, lower affinity site in HEK293 cells expressing h5-HT(1A) receptors but did not bind to native tissue 5-HT(1A) receptors. These data suggest that, in transfected HEK293 cells, human 5-HT(1A) receptors exist in different affinity states but in native rat cortical tissue the majority of receptors appear to exist in the high agonist affinity state. 3. Receptor agonists inhibited [(3)H]-MPPF binding from recombinant 5-HT(1A) receptors in a biphasic manner, whereas antagonists and partial agonists gave monophasic inhibition curves. All compounds displaced [(3)H]-8-OH-DPAT and [(3)H]-spiperone binding in a monophasic manner. In rat cortex, all compounds displaced [(3)H]-MPPF and [(3)H]-8-OH-DPAT in a monophasic manner. 4. Functional evaluation of compounds, using [(35)S]-GTPgammaS binding, produced a range of intrinsic activities from full agonism, displayed by 5-HT and 5-CT to inverse agonism displayed by spiperone. 5. [(3)H]-8-OH-DPAT : [(3)H]-MPPF pK(i) difference correlated well with functional intrinsic activity (r=0.86) as did [(3)H]-8-OH-DPAT : [(3)H]-spiperone pK(i) difference with functional intrinsic activity (r=0.96). 6. Thus agonist : antagonist binding affinity differences may be used to predict functional efficacy at human 5-HT(1A) receptors expressed in HEK293 cells where both high and low agonist affinity states are present but not at native rat cortical 5-HT(1A) receptors in which only the high agonist affinity state was detectable.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Characterization of the ORL(1) receptor on adrenergic nerves in the rat anococcygeus muscle.

1. Nociceptin, the endogenous ORL(1) receptor agonist inhibited the motor response to electrical-field stimulation in the rat anococcygeus muscle. This effect was characterized using the peptide ligands acetyl-Arg-Tyr-Tyr-Arg-Trp-Lys-NH(2) (Ac-RYYRWK-NH(2)), acetyl-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)) and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) ([F/G]NC(1-13)NH(2)), and the non-selective opioid antagonist naloxone benzoylhydrazone (NalBzOH). 2. Nociceptin produced a concentration-dependent inhibition of the adrenergic motor response to electrical-field stimulation (EC(50) 19 nM, pEC(50) 7.7+/-0.1, n=8), but the response to exogenous noradrenaline (0.2 - 1 microM) was unaffected. The inhibitory nerve response was not affected by up to 1 microM nociceptin. 3. After inhibition of nitric oxide synthase (N(omega)-nitro-L-arginine 100 microM), and in the presence of peptidase inhibitors, nociceptin produced full inhibition of the pure adrenergic motor response (EC(50) 4 nM; pEC(50) 8.4+/-0.1, E(max) 98.3+/-1.2%, n=12). Ac-RYYRWK-NH(2) was a potent partial-agonist (pEC(50) 9.0+/-0.1, E(max) 66.4+/-5.2; n=11) but the efficacy of Ac-RYYRIK-NH(2) (pEC(50) 8.0+/-0.2, E(max) 36.7+/-3.5; n=12) was lower and the peptide could be tested as an antagonist (pA(2) 9.01). 4. [F/G]NC(1-13)NH(2) and NalBzOH had little or no efficacy and were competitive antagonists with pK(B) values of 7.4 (95% c.l. 7.1, 7.7) and 6.9 (95% c.l. 6.7, 7.1) respectively. Both increased the response to field stimulation at high concentrations, suggesting the release of an endogenous agonist for the ORL(1) receptor during stimulation. 5. Rat nocistatin did not affect the response to electrical-field stimulation, nor did it modify the inhibitory action of nociceptin. 6. Our findings suggest there is a significant endowment of ORL(1) receptors on sympathetic terminals of the rat anococcygeus, where nociceptin mediates a powerful inhibitory effect on adrenergic neuromuscular transmission.

Anal Canal↗
PubMed2000

An observer-blinded comparison of supervised and unsupervised aerobic exercise regimens in fibromyalgia.

OBJECTIVE: To compare a supervised 12-week aerobic exercise class with unsupervised home aerobic exercises in the treatment of patients with fibromyalgia. METHODS: This was a 48-week randomized single (observer) blind study in a teaching hospital rheumatology and physiotherapy department. The subjects were 74 patients who fulfilled the American College of Rheumatology criteria for fibromyalgia. Results and conclusions. A 12-week exercise class programme with home exercises demonstrated no benefit over a single physiotherapy session with home exercises in the treatment of pain in patients with fibromyalgia. Neither group (nor the groups combined) showed an improvement in pain compared with baseline. There was some significant benefit in psychological well-being in the exercise class group and perhaps a slowing of functional deterioration in this group.

Exercise↗
PubMed2000

Differential modulation and subsequent blockade of mitogenic signaling and cell cycle progression by Pasteurella multocida toxin.

The intracellularly acting protein toxin of Pasteurella multocida (PMT) causes numerous effects in cells, including activation of inositol 1,4,5-trisphosphate (IP(3)) signaling, Ca(2+) mobilization, protein phosphorylation, morphological changes, and DNA synthesis. The direct intracellular target of PMT responsible for activation of the IP(3) pathway is the G(q/11)alpha-protein, which stimulates phospholipase C (PLC) beta1. The relationship between PMT-mediated activation of the G(q/11)-PLC-IP(3) pathway and its ability to promote mitogenesis and cellular proliferation is not clear. PMT stimulation of p42/p44 mitogen-activated protein kinase occurs upstream via G(q/11)-dependent transactivation of the epidermal growth factor receptor. We have further characterized the effects of PMT on the downstream mitogenic response and cell cycle progression in Swiss 3T3 and Vero cells. PMT treatment caused dramatic morphological changes in both cell lines. In Vero cells, limited multinucleation, nuclear fragmentation, and disruption of cytokinesis were also observed; however, a strong mitogenic response occurred only with Swiss 3T3 cells. Significantly, this mitogenic response was not sustained. Cell cycle analysis revealed that after the initial mitogenic response to PMT, both cell types subsequently arrested primarily in G(1) and became unresponsive to further PMT treatment. In Swiss 3T3 cells, PMT induced up-regulation of c-Myc; cyclins D1, D2, D3, and E; p21; PCNA; and the Rb proteins, p107 and p130. In Vero cells, PMT failed to up-regulate PCNA and cyclins D3 and E. We also found that the initial PMT-mediated up-regulation of several of these signaling proteins was not sustained, supporting the subsequent cell cycle arrest. The consequences of PMT entry thus depend on the differential regulation of signaling pathways within different cell types.

3T3 Cells↗
PubMed2000

Macrovascular disease and systemic sclerosis.

OBJECTIVE: To determine if macrovascular disease is more prevalent in systemic sclerosis (SSc) compared with unaffected subjects. METHODS: 54 patients with SSc (both limited and diffuse disease) and 43 unaffected control subjects of similar age and sex were recruited. All subjects underwent a basic screen for conventional atherosclerotic disease risk factors. All had non-invasive vascular assessments-that is, carotid duplex scanning and measurement of ankle brachial blood pressure index-to identify the presence of asymptomatic peripheral vascular disease. RESULTS: 33 of 52 (64%) patients had carotid artery disease compared with only 15 of 42 (35%) controls (p=0.007). Eleven (21%) of these patients had moderate disease compared with only two (5%) controls (NS). Nine of 53 (17%) SSc patients had evidence of peripheral arterial disease compared with no controls. This result was also statistically significant (p=0.003). There were no significant differences in the basic risk factor profile, which included cigarette smoking, systolic and diastolic blood pressure, cholesterol, trigyceride and glucose concentrations. CONCLUSION: Macrovascular disease is more common in SSc. Screening of these patients may allow identification of "at risk" patients at an early stage and allow the study of treatments to attenuate the high rate of cardiovascular mortality in these patients.

Adult↗
PubMed2000

Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression.

PURPOSE: The CAG repeat polymorphism of the androgen receptor gene has been associated with an increased prostate cancer risk, and the repeat length correlated with cancer stage and grade at presentation. Men with an allele length of </= 18 CAG repeats have a 2-fold increase in risk for high-stage or high-grade prostate cancer, compared with patients with a longer CAG repeat. We examined the significance of the CAG repeat polymorphism of the androgen receptor gene for predicting prostate cancer progression among 318 patients treated by radical prostatectomy for clinically localized prostate cancer between 1987 and 1994. MATERIALS AND METHODS: Leukocyte DNA was collected and genotyping of the CAG repeat polymorphism was performed using a PCR-based direct sequencing method. Risk ratios were calculated for developing biochemical recurrence for patients associated with an allele length of </= 18 CAG repeats, compared with patients with an allele length of >18 CAG repeats, controlling for grade, stage and serum PSA level at diagnosis using Cox proportional hazard modeling. RESULTS: Overall, the CAG repeat allele was not predictive of recurrence; tumor grade, stage and PSA level at diagnosis were the only predictors of recurrence in a multivariate analysis. However, for patients at low risk for recurrence (Gleason score 2 to 6, stage pT2, and PSA </= 10 ng./ml.), the relative risk of recurrence associated with an allele of </= 18 CAG repeats was 8.07 (95% C.I., 2.02 to 32.2, p = 0.004), compared with patients with an allele length of >18 CAG repeats. In contrast, for patients at high risk of recurrence (Gleason score >/= 7, stage pT3/4, or PSA >10 ng./ml.), the relative risk associated with the </= 18 CAG repeat allele was 0.72 (95% C.I., 0.33 to 1.57, p = 0.41), compared with patients with the >18 CAG repeat allele. CONCLUSIONS: The length of the CAG repeat polymorphism of the androgen receptor gene may be important for prostate cancer recurrence among patients who are otherwise at low risk for recurrence after radical prostatectomy. These findings have potential implications for patient selection for adjuvant treatment, and for the development of novel treatments.

Alleles↗
PubMed2000

Efficacy of directional coronary atherectomy before stent implantation for coronary ostial lesions.

We evaluated stent implantation following directional coronary atherectomy (DCA) for coronary ostial lesions. The subjects were 27 patients (27 lesions) who underwent stent deployment after DCA, and 47 patients (47 lesions) who underwent stent deployment alone as the control group. There were no differences in numbers of lesions with multi-vessel disease, left anterior descending artery lesions, de novo lesions or reference vessel diameters in the two groups. The percent diameter stenosis after stent implantation was lower in the DCA-stent group than in the stent-alone group (9 +/- 10% versus 17 +/- 14%, respectively; p < 0.01). The initial procedural success rate was 92.6% in the DCA-stent group and 91.4% in the stent-alone group. The initial clinical success rate was 100% in the DCA-stent group and 95.7% in the stent-alone group. The restenosis rate was lower in the DCA-stent group (20% versus 43% in the stent-alone group). This study showed that debulking by DCA before stenting is more effective compared to stenting alone.

Aged↗