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J Williams

Publications and source records attributed to J Williams.

At least 451 records · Page 25Linked to original sources
PubMed1996

Correlation of ELISA-detected IgG and IgA anti-HLA antibodies in pretransplant sera with renal allograft rejection.

The present study compared the occurrence of rejection episodes during the first twelve posttransplant (Tx) months and the 1-, 2-, and 3-year graft survivals among recipients stratified by the percent panel reactive antibody (% PRA) of pre-Tx sera as detected using either an antihuman globulin determined PRA (AHG-% PRA) or an ELISA methodology detecting IgG reactive against soluble HLA class I antigens (% PRA-STAT). There was a significant correlation between AHG-PRA greater than or equal to 10% and a PRA-STAT greater than or equal to 10% (P<0.001). However, among 200 sera displaying an AHG-PRA greater than or equal to 10% (mean 57 +/- 2l%), only 69% (138/200) displayed a PRA-STAT greater than or equal to 10%. With further study the discrepant finding, of 62 sera that were AHG-PRA greater than or equal to 10% but PRA-STAT <10%, was due to the presence of IgM and/or IgG non-MHC reactivity. In contrast, among 293 sera displaying an AHG-PRA < 100% (mean 3 +/- 2%), 15% (43/293) displayed a PRA-STAT greater than or equal to 10%. There was no correlation between AHG-% PRA and rejection episodes occurring during the first twelve post Tx months. In contrast, however, there was a highly significant correlation between PRA-STAT greater than or equal to 10% and the occurrence of rejection episodes during the first twelve post-Tx months (P < 0.001). Patients with PRA-STAT greater than of equal to 10% experienced a 70% rejection frequency compared with the 35% rejection frequency for patients with PRA-STAT sera < 10% (P<0.001). A significant correlation was observed between the presence of IgG-1 and rejection (P<0.01) but not IgG-subclasses 2, 3, or 4. Of particular interest was the observation in 11 patients that the presence of ELISA-detected IgA anti-HLA class I antigen (ELISA-IgA PRA greater than or equal to 10%) was associated with a significantly reduced rejection risk compared with sera where only PRA-STAT greater than or equal to 10% was present (27% vs. 70% incidence of rejection episodes, P<0.01). Finally, patients displaying pretransplant PRA-STAT results < 10% experienced significantly improved l-, 2-, and 3- year graft survivals of 85% vs. 74%, 82% vs. 70% and 81% vs. 67%, respectively (P<0.01 for each time point), compared with patients displaying PRA-STAT results greater than or equal to 10%. These data suggest that the use of the ELISA methodology to detect IgG reactivity against soluble HLA class I antigens (PRA-STAT) may allow for the determination of a more clinically informative % PRA than the AHG-% PRA. Moreover, the presence of ELISA-detected IgA anti-HLA may act to inhibit rejection mechanisms associated with ELISA-detected IgG anti-HLA greater than or equal to 10%.

Enzyme-Linked Immunosorbent Assay↗
PubMed1996

Delayed xenograft rejection in the concordant hamster heart into Lewis rat model.

The inability to provide an adequate supply of human organs for clinical transplantation has created a strong interest in the use of nonhuman, especially nonprimate, organs. The first biological obstacle confronting such discordant transplantations is a series of violent reactions that result in hyperacute rejection of the xenograft. Significant advances in controlling hyperacute rejection have been achieved recently through the generation of transgenic pig donors bearing human complement regulatory proteins. However, when hyperacute rejection is averted, the xenografts are rejected in 2-70 days in spite of high-dose immunosuppression, by a process collectively termed delayed xenograft rejection. Delayed xenograft rejection is characterized by a refractoriness to conventional immunosuppression, extensive xenoreactive antibody deposition, and cellular infiltration that is dominated by macrophages. We have examined the features of extended host and graft response in the concordant hamster-to-rat xenotransplant model, where such features have historically been obscured by early graft destruction. Hamster hearts transplanted into rats do not encounter hyperacute rejection but are rejected within 3-4 days when xenoreactive antibody titers rise exponentially to levels that elicit a classical antibody- and complement-mediated acute xenograft rejection. We have successfully blocked acute xenograft rejection by a combination of immunosuppressive agents, leflunomide, and cyclosporine. Stopping the immunosuppression resulted in graft rejection that is histologically characterized by extensive xenoreactive antibody deposition and cellular infiltration that is predominantly composed of macrophages. We have noted the similarities between the histopathology of rejection of long-surviving concordant xenografts and that described for discordant xenografts and refer to the process of rejection of concordant grafts that have escaped acute xenograft rejection, delayed xenograft rejection.

Acute Disease↗
PubMed1996

Structure of diferric duck ovotransferrin at 2.35 A resolution.

The structure of diferric duck ovotransferrin (DOT) has been determined and refined at a resolution of 2.35 A. The DOT structure, which contains two iron binding sites, is similar to the known transferrin and lactoferrin structures. The two iron-binding sites, one in the N-terminal lobe and one in the C-terminal lobe of the molecule, are similar but not identical. The main differences between the three known structures lie in the relative orientations of the N- and C-lobes with respect to each other. In the DOT structure the large aromatic side chain of Phe322 in the N-lobe packs against the conserved residue Gly387 in the C-lobe. This interaction is at the centre of the interface between the two lobes and could play a crucial role in determining their relative orientation. Other differences between the structures occur in the surface loops and in the peptide connecting the two lobes. The final crystallographic model consists of 5309 protein atoms (686 residues), two Fe(3+) ions, two (bi)carbonate ions and three carbohydrate moities. 318 water molecules have been added to the model. The final R factor is 0.22 for 25 400 observed reflections between 10 and 2.35 A resolution.

Journal Article↗
PubMed1996

Evidence that a combined activator-repressor protein regulates Dictyostelium stalk cell differentiation.

The ecmA gene is expressed in Dictyostelium prestalk cells and is inducible by differentiation-inducing factor (DIF), a low-molecular-weight lipophilic substance. The ecmB gene is expressed in stalk cells and is under negative control by two repressor elements. Each repressor element contains two copies of the sequence TTGA in an inverted relative orientation. There are activator elements in the ecmA promoter that also contain two TTGA sequences, but in the same relative orientation. Gel retardation assays suggest that the same protein binds to the ecmB repressor and the ecmA activator. We propose that DIF induces prestalk cell differentiation by activating this protein and that the protein also binds to the promoters of stalk-specific genes, acting as a repressor that holds cells in the prestalk state until culmination is triggered.

Animals↗
PubMed1996

Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group.

BACKGROUND: An association between schizophrenia and the T102C polymorphism of the gene for 5-hydroxytryptamine type 2a (5-HT2a) receptor has been reported; the proportion of allele 2 of this polymorphism is higher than expected among schizophrenic patients. We looked for an association between schizophrenia and this variant of the 5-HT2a-receptor gene in a large multicentre study. METHODS: Seven countries recruited 1210 participants: 571 white schizophrenic patients and 639 ethnically matched controls. All patients had a diagnosis of schizophrenia or schizoaffective disorder. High-molecular-weight DNA was isolated from lymphocytes. PCR amplification and restriction enzyme digestion was used to examine sequence variation of the 5-HT2a-receptor gene. Genotypes 1/1, 1/2, and 2/2 were assigned. Woolf's method was used to look for an association between schizophrenia and allele 2 and the 2/2 genotype. FINDINGS: We found a significant overall association between schizophrenia and allele 2 with an odds ratio of 1.3 (95% Cl 1.1-1.53, p = 0.003). No evidence for heterogeneity was observed between samples. We found a highly significant excess of the 1-2/2-2 genotypes in schizophrenia (p = 0.008) with a relative risk of 1.7 (1.22-2.36) and an attributable fraction of 0.35. INTERPRETATION: Our findings suggest that the gene for 5-HT2a-receptor, or a locus in linkage disequilibrium with it, confers susceptibility to schizophrenia. Allele 2 is common in the population and it is, therefore, likely that this variant, or a nearby polymorphism, may affect a significant proportion of schizophrenic patients.

Alleles↗
PubMed1996

Do splanchnic viscera contribute to liver preservation reperfusion injury?

Preservation-reperfusion injury of hepatic allografts is thought to be associated with Kupffer cell activation and TNF release from the transplanted organ. Confirmation that the allograft is the source of this TNF in an in vivo model is difficult because of rapid equilibration of this cytokine into all compartments. A novel experimental design was devised to aid in accurate localization of the site of TNF release following a orthotopic liver transplant (OLT). In the first group (anhepatic), livers were removed from rats and splanchnic and systemic venous returns were then reestablished using a conduit of donor IVC and portal vein with a portasystemic shunt. In the second group (asplanchnic), the liver, stomach, pancreas, and intestine of the recipient were removed and a donor liver was reimplanted using the recipient IVC as the source of portal blood. The third (OLT-16) and fourth (OLT 8) groups underwent standard OLT with preservation times of 16 and 8 hr in 4 degrees C Euro-Collins solution, respectively. TNF levels were significantly increased in the OLT-16 group compared with the OLT-8 group. There were modest elevations of TNF in the anhepatic model, but the TNF in the asplanchnic model approached baseline. Absence of TNF in the asplanchnic group and a rise in TNF levels in the anhepatic group to that not significantly different from OLT-16 or OLT-8 suggest that a major source of TNF following preservation reperfusion may be the intestine.

Animals↗
PubMed1996

A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine.

OBJECTIVE: To stop an epidemic of hepatitis A in rural Alaska by mass immunization of susceptible persons with 1 dose of an inactivated hepatitis A vaccine. DESIGN: Nonrandomized, uncontrolled trial. Hepatitis A vaccine was offered to all persons in susceptible age groups in villages with documented cases of hepatitis A. Immune globulin was not offered at the time of vaccination. SETTING: Twenty-five rural communities located in interior Alaska and along the northwest coast of the Bering Sea and Arctic Ocean. PARTICIPANTS: Persons without a history of acute hepatitis A in age groups selected by applying results of a previous serosurvey conducted on serum collected before the epidemic. INTERVENTION: One dose of a formalin-inactivated hepatitis A vaccine was given to each participant. Adults 20 years of age and older received 1440 enzyme-linked immunosorbent assay units and persons younger than 20 years received 720 enzyme-linked immunosorbent assay units. Prevaccination and postvaccination levels of antibody to hepatitis A IgG were obtained from 136 participants. MAIN OUTCOME MEASURES: An active surveillance system was established to detect persons with symptomatic illnesses compatible with hepatitis A; persons who met the illness criteria were tested for antibody to hepatitis A IgM. One area (the Kotzebue region), where all communities were offered vaccine, was selected for intensive surveillance and analysis. RESULTS: During the 12-month period before the vaccine trial, 529 cases of icteric hepatitis A were reported, and 443 were confirmed to be positive for antibody to hepatitis A IgM. Hepatitis A vaccine was administered to 4930 persons, 3517 of whom were younger than 20 years. After vaccination began, 237 persons positive for antibody to hepatitis A IgM were identified during a 60-week surveillance period; 46 were vaccines and 191 were unvaccinated susceptible persons. In the Kotzebue region, in communities in which more than 80% of persons considered susceptible were vaccinated, the outbreak ceased in 4 to 8 weeks, whereas in 1 large community in which less than 50% of susceptible persons were vaccinated, the outbreak continued for more than 50 weeks. More than 90% of seronegative persons developed antibody to hepatitis A IgG 3 to 4 weeks after vaccination. CONCLUSION: This trial suggested that by providing both short-term and long-term protection, hepatitis A vaccine used without immune globulin halted an established epidemic of hepatitis A in rural Alaska.

Adolescent↗
PubMed1996

Bone mass, areal, and volumetric bone density are equally accurate, sensitive, and specific surrogates of the breaking strength of the vertebral body: an in vitro study.

The validity of the bone mineral density (BMD) measurement depends on its accuracy as a predictor of the breaking strength of bone. As the breaking strength is proportional to the square of the apparent density, a small error in the calculation of BMD may result in a larger error in the predicted bone strength. The aims of this study were (i) to determine whether inaccuracies in the measurement of the dimensions, projected area, and volume of the vertebral body (used to derive the areal and volumetric BMD) result in errors in the predicted breaking strength and (ii) to compare the accuracy, sensitivity, and specificity of bone mineral content (BMC), areal BMD, volumetric BMD, and volumetric bone mineral apparent density (BMAD) as surrogates of bone strength. We measured the BMC (by densitometry), dimensions and volume (using calipers, densitometry, the Carter et al. and Peel and Eastell methods), and breaking strength (using the Instron 1114 apparatus, Newtons, N) of 22 vertebral body specimens. All methods resulted in errors in height, width, and depth between -11.3 +/- 1.0 and 30.4 +/- 1.8% relative to the "gold" standard caliper method. The vertebral body volume (of 38.0 +/- 1.2 cm3) measured by submersion was used as the gold standard to derive the volumetric BMD gold standard (of 0.162 +/- 0.01 g/cm3). All methods, except the Peel and Eastell method, resulted in errors ranging between -10.7 +/- 1.5 and 56.9 +/- 3.4% in vertebral body volume and -35.6 +/- 1.5 to 12.6 +/- 1.8% in volumetric BMD (all p < 0.0005). The same absolute value for volumetric BMD predicted a breaking strength that differed according to the method used to derive BMD. For example, a volumetric BMD of 0.162 g/cm3 predicted a breaking strength of 6208 N (submersion method), 5473 N (caliper method), 6095 N (Peel and Eastell method), 7697 N (DXA method), and 9470 N (Carter et al. method). The mean volumetric BMD derived by each method differed (0.181, 0.165, 0.133, and 0.104 g/cm3, respectively). However, all were accurate; each predicted a similar breaking strength (6177, 6217, 6209, and 6221 N respectively). Likewise, breaking strengths predicted by the mean BMC, areal BMD by calipers, and areal BMD by dual-energy X-ray absorptiometry (DXA) were 6267, 6214, and 6244 N, respectively. The methods were equally sensitive; a 1 standard deviation (SD) decrease in volumetric BMD resulted in a similar decrease in the breaking strength of 1818 (caliper), 2080 (Peel and Eastell), 2001 (DXA), and 1625 N (BMAD by Carter et al). A 1 SD decrease in BMC, areal BMD (using calipers) and areal BMD (using DXA) predicted a decrease in the breaking strength of 2019, 1738, and 1825 N, respectively. All methods were equally specific; the variance in bone strength explained by bone mass did not differ for volumetric BMD (38-61% depending on the method), BMC (58%), or areal BMD (48%). In conclusion, despite errors in the measurement of the dimensions of the vertebral body, bone mass, areal, and volumetric bone density are equally accurate, sensitive, and specific surrogates of the breaking strength of bone in vitro.

Absorptiometry, Photon↗
PubMed1996

Seasonal variation of LH, sex steroids, body mass, molt, display, and laying in two subspecies of Houbara bustard, Chlamydotis undulata macqueenii and Chlamydotis undulata undulata, housed in outdoor cages under natural conditions.

Subspecies of the Houbara bustard are resident in North Africa (Chlamydotis undulata undulata) or are partial latitudinal migrants in Asia (Chlamydotis undulata macqueenii). Houbara breed in arid or semiarid zones, and the reproductive biology of wild Houbara is largely unknown. Body mass, molt, courtship display, laying, and plasma concentrations of LH, testosterone, and progesterone were measured in captive-bred birds of both subspecies, housed in outdoor cages under natural conditions, over a period of 1 year and 6 months, at Taif, Saudi Arabia (21 degrees 15' N). Captive Houbara bustards show a seasonal breeding pattern with a laying period from January to July. Males began displaying well in advance of any eggs laid and display long after the termination of laying. In females, gonadal activity and molt were mutually exclusive; however, in males, slight overlap between sexual display and molt was observed. In females, seasonal variation of LH and progesterone was synchronous with laying activity. In males both testosterone and LH plasma concentrations were highest in January (testosterone approximately 8 ng/ml; LH approximately 3 ng/ml) at the beginning display period. This could correspond, in the wild, to the establishment of territories. Levels dropped significantly before the females started laying but stayed at an intermediate level throughout the breeding season (testosterone approximately 3 ng/ml; LH approximately 1.5 ng/ml). In the middle of August, during molt, and following heavy rainfall, LH and testosterone peaked (testosterone approximately 2.3 ng/ml; LH approximately 1.8 ng/ml), suggesting a possible impact of rainfall on Houbara gonadal activity. Houbara stopped laying before the maximum ambient temperature reached 32 degrees, indicating that high temperature could be a factor terminating laying activity. No major differences were found between the two subspecies in the timing or duration of the reproductive period; only the annual variation of the body mass varied slightly between the subspecies.

Animals↗
PubMed1996

A multirater validation study to assess the reliability of acne lesion counting.

BACKGROUND: Despite widespread use of acne lesion counting, little has been published on its reliability, particularly for multiple raters. OBJECTIVE: Our purpose was to assess reliability of acne lesion counting with the use of a five-segment facial template. METHODS: After training, 12 raters each evaluated 12 patients in randomized order, in the morning and again in the afternoon, and recorded counts for different types of lesions on a five-segment facial template. RESULTS: Individual raters could reproduce their total lesion counts (reliability estimates, 0.81 to 0.97). Variability between raters was high, and overall reliability estimated across raters was 0.61. For a subgroup of commonly trained raters, overall reliability was higher (0.80). CONCLUSION: The reliability of acne lesion counting is excellent when performed by the same trained rater over time. The high variability between raters appears to be reduced by standardized training. Because fewer lesions are counted with less variation, use of a template may have contributed to the high within-rater reliability.

Acne Vulgaris↗
PubMed1996

Nurses referred to a peer assistance program for alcohol and drug problems.

Investigation into nurses referred to peer assistance programs for substance abuse is essential to program development and the development of primary prevention strategies. The purpose of this study was to (1) describe the characteristics, substance use, and program participation of 221 nurses referred to a state nursing organization peer assistance program, and (2) identify factors associated with program participation. The highest percentage of nurses (63%) used narcotics; 36% had diverted drugs from patients for their own use. Sixty-four percent of the referred nurses successfully completed the program. This model was found to be effective in addressing substance abuse in nursing.

Adult↗
PubMed1996

Feasibility of using a swine portal vein containing a metallic stent for creating a portacaval shunt.

RATIONALE AND OBJECTIVES: We evaluated the feasibility of using a metallic stented portal vein as a conduit for portacaval shunt in pigs. METHODS: A metallic self-expanding stent was placed in the portal vein of five pigs under combined ultrasound and fluoroscopic guidance via a percutaneous transhepatic approach. After 6 weeks, a portacaval shunt was performed using the stented portal vein as a conduit. A single angiogram followed immediately by sacrifice and histologic examination was performed on each pig at a varying time interval postshunt. RESULTS: One pig died 3 days after the shunt procedure because of a presumed surgical technical failure and a consequent thrombosed portal vein. Angiographic patency of the portacaval shunt was confirmed in the four remaining pigs. Postmortem histologic evaluation showed more complete endothelialization and subintimal organization in the more chronic stents. Thrombus occurred only in the stent of the pig that died. There was no significant luminal obstruction in the other four stents. CONCLUSION: Our results suggest that a stented portal vein can be used successfully as a conduit for portacaval shunt in pigs.

Angiography↗