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Biomedical subjects

K King

Publications and source records attributed to K King.

At least 19 recordsLinked to original sources
PubMed2006

Sequence variation, linkage disequilibrium and association with Crohn's disease on chromosome 5q31.

Chromosome 5q31 contains a cluster of genes involved in immune response, including a 250 kb risk haplotype associated with Crohn's disease (CD) susceptibility. Recently, two functional variants in SLC22A4 and SLC22A5 (L503F and G-207C), encoding the cation transporters OCTN1 and OCTN2, were proposed as causal variants for CD, but with conflicting genetic evidence regarding their contribution. We investigated this locus by resequencing the coding regions of 10 genes in 24 CD cases and deriving a linkage disequilibrium (LD) map of the 27 single nucleotide polymorphisms (SNPs) detected. Ten SNPs representative of the LD groups observed, were tested for CD association. L503F in SLC22A4 was the only nonsynonymous SNP significantly associated with CD (P=0.003), but was not associated with disease in the absence of other markers of the 250 kb risk haplotype. Two other SNPs, rs11242115 in IRF1 and rs17166050 in RAD50, lying outside the 250 kb risk haplotype, also showed CD association (P=0.019 and P=0.0080, respectively). The RAD50 gene contains a locus control region regulating expression of the Th2 cytokine genes at this locus. Other as yet undiscovered SNPs in this region may therefore modulate gene expression and contribute to the risk of CD, and perhaps of other inflammatory phenotypes.

Base Sequence↗
PubMed2004

Regulation of 5alpha-reductase isoforms by oxytocin in the rat ventral prostate.

Oxytocin (OT) is present in the male reproductive tract, where it is known to modulate contractility, cell growth, and steroidogenesis. Little is known about how OT regulates these processes. This study describes the localization of OT receptor in the rat ventral prostate and investigates if OT regulates gene expression and/or activity of 5alpha-reductase isoforms I and II. The ventral prostates of adult male Wistar rats were collected following daily sc administration of saline (control), OT, a specific OT antagonist or both OT plus antagonist for 3 d. Expression of the OT receptor was identified in the ventral prostate by RT-PCR and Western blot, and confirmed to be a single active binding site by radioreceptor assay. Immunohistochemistry localized the receptor to the epithelium of prostatic acini and to the stromal tissue. Real-time RT-PCR determined that OT treatment significantly reduced expression of 5alpha-reductase I but significantly increased 5alpha-reductase II expression in the ventral prostate. Activity of both isoforms of 5alpha-reductase was significantly increased by OT, resulting in increased concentration of prostatic dihydrotestosterone. In conclusion, OT is involved in regulating conversion of testosterone to the biologically active dihydrotestosterone in the rat ventral prostate. It does so by differential regulation of 5alpha-reductase isoforms I and II.

Animals↗
PubMed2003

Dietary P regulates phosphate transporter expression, phosphatase activity, and effluent P partitioning in trout culture.

Phosphate utilization by fish is an important issue because of its critical roles in fish growth and aquatic environmental pollution. High dietary phosphorus (P) levels typically decrease the efficiency of P utilization, thereby increasing the amount of P excreted as metabolic waste in effluents emanating from rainbow trout aquaculture. In mammals, vitamin D3 is a known regulator of P utilization but in fish, its regulatory role is unclear. Moreover, the effects of dietary P and vitamin D3 on expression of enzymatic and transport systems potentially involved in phosphate utilization are little known. We therefore monitored production of effluent P, levels of plasma vitamin D3 metabolites, as well as expression of phosphatases and the sodium phosphate cotransporter (NaPi2) in trout fed semipu diets that varied in dietary P and vitamin D3 levels. Mean soluble P concentrations varied markedly with dietary P but not with vitamin D3, and constituted 40-70% of total effluent P production by trout. Particulate P concentrations accounted for 25-50% of effluent P production, but did not vary with dietary P or vitamin D3. P in settleable wastes accounted for <10% of effluent P. The stronger effect of dietary P on effluent P levels is paralleled by its striking effects on phosphatases and NaPi2. The mRNA abundance of the intestinal and renal sodium phosphate transporters increased in fish fed low dietary P; vitamin D3 had no effect. Low-P diets reduced plasma phosphate concentrations. Intracellular phytase activity increased but brushborder alkaline phosphatase activity decreased in the intestine, pyloric caeca, and gills of trout fed diets containing low dietary P. Vitamin D3 had no effect on enzyme activities. Moreover, plasma concentrations of 25-hydroxyvitamin D3 and of 1,25-dihydroxyvitamin D3 were unaffected by dietary P and vitamin D3 levels. The major regulator of P metabolism, and ultimately of levels of P in the effluent from trout culture, is dietary P.

6-Phytase↗
PubMed2003

Genetic variation in the IGSF6 gene and lack of association with inflammatory bowel disease.

The immunoglobulin superfamily 6 gene (IGSF6) on chromosome 16p11-p12 has been investigated as a positional and functional candidate for inflammatory bowel disease (IBD) susceptibility. Screening of the six exons of IGSF6 for single nucleotide polymorphisms (SNPs) detected four novel SNPs, and validated three of six SNPs listed in the international SNP database (dbSNP). The seven SNPs in IGSF6 formed five distinct linkage disequilibrium groups. There was no evidence for association of the common SNPs with disease in a large cohort of patients with IBD. The novel SNPs and the linkage disequilibrium map will be a useful resource for the analysis of IGSF6 in other immune disorders.

CD8 Antigens↗
PubMed2002

Trimetrexate in relapsed T-cell lymphoma with skin involvement.

PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX) enters cells by passive diffusion and is not polyglutamylated, its activity in relapsed T-cell lymphoma was investigated. PATIENTS AND METHODS: Eligible patients had histologically confirmed relapsed T-cell lymphoma involving the skin, had received more than one previous regimen, were older than 16 years, had normal organ function, and had no CNS disease or serious infections, including human immunodeficiency virus. TMTX (200 mg/m(2)) was given intravenously every 14 days without topical or systemic corticosteroids. Patients who responded received up to 12 doses. RESULTS: Twenty patients were assessable for response. Median age was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sézary syndrome (14 with large-cell transformation), and two had peripheral T-cell lymphoma. Serum lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0 mg/L in 35% of patients. The median number of previous regimens was three (range, two to 15) and included MTX in five patients. Disease was refractory to the regimen immediately preceding TMTX in 85% of patients. Responses were complete in one and partial in eight patients (overall response rate, 45%). Two of five patients previously treated with MTX responded. Grade 3 or 4 mucositis was observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils less than 100/microL after 4%, and platelets less than 10,000/microL after 3% of TMTX doses. CONCLUSION: TMTX is active with acceptable toxicity in this population and merits further investigation.

Aged↗
PubMed2001

Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.

Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.

Alleles↗
PubMed2001

Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.

Adult↗
PubMed2001

Single-donor platelets reduce the risk of septic platelet transfusion reactions.

BACKGROUND: Septic platelet transfusion reactions (SPTRs) are the most common, serious risk of transfusion. Because SPTRs result from donor skin flora or asymptomatic bacteremia, the use of single-donor platelets (SDPs) has been proposed to reduce the risk of SPTRs from the risks with pools of platelet concentrates (PCs). STUDY DESIGN AND METHODS: Beginning in 1986, all febrile transfusion reactions were evaluated by culture of the platelet bag. Confirmed SPTRs were identified by isolation of the same bacteria from the bag and the patient's blood or by positive Gram's stain of the bag that confirmed a positive platelet culture. In 1987, a program to minimize PC use in favor of SDP use was initiated as a means of reducing SPTRs. RESULTS: In 12 years, the use of SDPs increased from 51.7 percent to 99.4 percent of all platelet transfusions at one institution. SPTRs fell from three events in 1 year to the current rate of one event per year. The incidence of SPTRs decreased from 1 in 4,818 transfusions to 1 in 15,098 transfusions. The rate of SPTRs due to PCs was 5.39 times higher than that of SPTRs due to SDPs (95% CI, 1.89,12.9). CONCLUSION: The use of SDPs is a simple means of reducing SPTRs. Other measures such as sterilization will be required to eliminate all SPTRs.

Adult↗
PubMed2001

Attitudes of patients toward cardiopulmonary resuscitation in the dialysis unit.

Some dialysis units have a policy of performing cardiopulmonary resuscitation (CPR) on all patients who experience cardiac arrest while undergoing dialysis. However, to perform CPR on patients who do not want it is contrary to ethics and the law. We interviewed hemodialysis patients in 12 units in Missouri, New York, and West Virginia to learn their attitudes about CPR. Four hundred sixty-nine of 830 patients (57%) agreed to be interviewed. Eighty-seven percent of patients wanted to undergo CPR if cardiac arrest were to occur while undergoing dialysis. Patients who had seen CPR on television were more likely to report that they knew what CPR was (94% versus 68%; P < 0.001) and to want CPR (88% versus 78%; P = 0.033). Thirteen percent of patients did not want CPR if cardiac arrest were to occur while undergoing dialysis. Compared with patients who wanted CPR, those who did not were older (69 versus 59 years; P = 0.026), had more comorbid conditions (2.0 versus 1.5 comorbid conditions; P = 0.016), and were more likely to have a living will (61% versus 43%; P = 0.01), be widowed (36% versus 20%; P = 0.026), and live in a nursing home (9% versus 3%; P = 0.017). Blacks were significantly more likely to want CPR than whites (adjusted odds ratio, 6.56; 95% confidence interval, 2.57 to 22.27). Only 20 of 58 patients (35%) who did not want CPR were certain they had a do-not-resuscitate order in their dialysis chart. Ninety-two percent of patients who wanted CPR agreed that patients who did not want CPR should have their wishes respected by the dialysis unit. We conclude that most dialysis patients want to undergo CPR, but also want other patients' preferences not to be resuscitated to be respected. Dialysis units need to do a better job of identifying patients who prefer not to be resuscitated and respecting their wishes in the event of cardiac arrest while undergoing dialysis. Most importantly, nephrologists and dialysis unit staff need to educate dialysis patients about the poor outcomes with CPR so that dialysis patients' decisions about CPR are informed.

Aged↗
PubMed2001

Personality profile and neuropsychological test performance in chronic cocaine-abusers.

Little is known about the association between personality disorders and neuropsychological test performance in chronic cocaine users. The aims of the present study were to (1) pinpoint the specific neuropsychological characteristics of chronic cocaine abusers, (2) analyze their personality profile, and (3) explore the association between personality traits and neuropsychological test performance. A sample of 42 drug-abusers (mean age = 34.15; SD = 6.73; mean educational level = 11.44; SD = 2.01) was selected from a state rehabilitation facility and was compared to a control group (mean age = 34.53; SD = 9.01; mean educational level = 12.29; SD = 1.31). The following information was collected for each subject: (1) A clinical history adapted from Horton (1996). (2) The Personality Assessment Inventory (PAI) (Morey, 1991). (3) A neuropsychological test battery including: Arithmetic and Digits subtests from the WAIS-R, California Verbal Learning Test, Trial Making Test, Verbal Fluency tests, Rey-Osterrieth Complex Figure, Wisconsin Card Sorting Test, Benton Visual Retention Test, Stroop Neurological Screening Test and Hooper Visual Organization. Thirty-seven of the drug-dependent subjects obtained an abnormal score in at least one PAI scale. The personality profile of the drug-dependent subjects found via the PAI pointed to a Borderline/Antisocial personality, frequently associated with mania features. In six of the drug-abusers, a normal personality profile was observed. Neuropsychological test performance scores were within the low average or borderline range. The most abnormal scores were observed in attention, memory, and executive functioning tests. The results did not show any robust association between personality profile and neuropsychological test performance.

Adult↗
PubMed2000

Racial differences in response to acute dosing with hydrochlorothiazide.

Blacks demonstrate a higher response rate to diuretic therapy for hypertension than do whites. This study examined the pharmacokinetic (PK), pharmacodynamic, and neurohumoral effects of hydrochlorothiazide (HCTZ) administration in a matched group of 9 black and 9 white hypertensive patients (mean +/- SD for black and white). After a 4-week washout period and 7-day control diet, subjects received a single dose of HCTZ (25 mg at 8 AM) with serial blood and urine collections for 36 hours. After HCTZ sodium excretion increased comparably in both groups (blacks: 122 +/- 42 pre to 265 +/- 49 mEq/24 hours post; whites: 117 +/- 29 pre to 255 beta 39 mEq/24 hrs post). Potassium excretion tended to be higher at baseline and was significantly higher following HCTZ in whites (blacks: 45 beta 20 pre to 66 beta 13 mEq at 24 hours post; blacks: 57 +/- 9 pre to 86 +/- 14 mEq at 24 hours post) with most of the post-dosing difference being observed in the hours 0 to 12 after HCTZ. There were no between group PK differences for urinary HCTZ. Aldosterone excretion followed a normal circadian pattern in the whites but did not show this pattern in the blacks. Aldosterone excretion (0 to 12 hours) was generally lower post-dosing in blacks. In conclusion, whereas the PK and single-dose natriuretic response for HCTZ were not racially distinct, potassium excretion was notably less in blacks. Aldosterone excretion was also lower in blacks and without its normal circadian pattern which may, in part, explain their altered potassium excretion pattern.

Adult↗
PubMed2000

High dose rate brachytherapy to prevent recurrent benign hyperplasia in lung transplant bronchi: theoretical and clinical considerations.

BACKGROUND: Significant anastomotic stenosis and malacia is reported to affect 7% to 15% of lung transplant recipients. Laser debridement, dilation and stenting can be used effectively to treat the majority of these patients. However, persistent, as well as reactive hyperplastic tissue reaction, will occur in some of these patients, requiring multiple bronchoscopic interventions. The experience of 2 patients who received intraluminal brachytherapy irradiation to prevent recurrence of hyperplastic tissue causing airway obstruction is reported. Both had failed multiple attempts of local control, including wall stent, laser ablation and balloon dilation. They suffered from shortness of breath and progressive decrease in quality of life because of airway obstruction. METHODS: Two patients received intraluminal irradiation immediately following removal of severe post-lung transplant obstruction. Both patients developed airway obstruction 3 to 4 months after left lung transplantation. High Dose Rate (HDR) brachytherapy (192Ir). Afterloader was used to treat Patient 1 on two occasions. Patient 2 required a single treatment. The radiation dose of 3Gy/fraction was calculated at 1 cm from the catheter for all applications. RESULTS: Follow up for both patients included bronchoscopy at 3 weeks, 3 months and 6 months after radiation therapy. Follow up for Patient 1 is 7 months, and patient 2 is 6 months. Each patient had an initial complete response after radiation. There were no treatment-related complications, and both patients experienced significant improvement in respiratory function. CONCLUSIONS: Symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal radiation therapy. Patients who develop recurrent benign granulation tissue after stent and laser therapy may be considered for this type of treatment.

Aged↗
PubMed2000

Probeliatrade mark PCR system for rapid detection of Salmonella in milk powder and ricotta cheese.

The Probeliatrade mark Salmonella sp. PCR amplification and detection kits (Sanofi Diagnostics Pasteur, Marnes La Coquette, France) were evaluated for the rapid and specific detection of Salmonella agona artificially inoculated into skim milk powder and ricotta cheese. The Probeliatrade mark results were compared with those obtained using the Australian Standard Method. Using a pure culture of Salm. agona, the detection limit of Probeliatrade mark was between 8 and 79 cfu ml-1, equivalent to 0.2-2 cfu per PCR reaction. Detection of Salm. agona inoculated in skim milk powder (at 5-10 cfu g-1, stored at 5, 15 or 25 degrees C) and ricotta cheese (at 1-2, 10-20 and 100-200 cfu per 25 g) was effected by using non-selective enrichment prior to the PCR determinations. For all of the 40 milk powder samples and 12 ricotta cheese samples, the Probeliatrade mark results were consistent with those using the Australian Standard Method. Using Probeliatrade mark, Salmonella was detected to genus level in the dairy products within 24-28 h, whereas the cultural technique required 3-4 d for presumptive positive isolates and further time for confirmation.

Animals↗