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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 361 records · Page 20Linked to original sources
PubMed1994

Preliminary characterization of lymphoid hybridoma cell lines derived from the pregnant mouse uterus.

Seven independent cell lines were derived from the fusion of migratory cells recovered from explant cultures of metrial glands to SP 2/0, a non-Ig secreting B cell myeloma. The migrating cells came from a pool of metrial glands from day 6-8 pregnant random bred CD1 mice and were assumed to be cells early in the differentiation pathway to granulated metrial gland (GMG) cells. The fused cells were cloned twice at the limiting dilution. Hybridization was confirmed by quantitation of cellular DNA using propidium iodide staining and by karyotyping. Electron microscopy revealed that each of the hybrid cell lines was composed of cells which were lymphoid in appearance, but lacked the granules found in mature GMG cells. The surface phenotype of all lines is CD45+, LGL-1-, asialo GM-1-, IgG-, IgM-, CD3- and CD25- (p55 of IL-2 receptor). Although the hybridomas lack those phenotypic markers which were used to show that GMG cells are related to the natural killer (NK) cell lineage (ie LGL-1, asialo GM-1), they do express the pan-leukocyte marker CD45 as well as the lytic protein, perforin, at levels intermediate to those of SP 2/0 cells and GMG cells. In addition, the hybridomas were observed to preferentially bind the NK target cell YAC and to be capable of lytic activity at temperatures below 30 degrees C. Because these hybridomas may represent fusion to an early progenitor cell of the NK/GMG cell lineage, their continued characterization is of merit.

Animals↗
PubMed1994

The importance of dose scheduling with mitoxantrone, 5-fluorouracil and leucovorin in metastatic breast cancer.

We have studied a mitoxantrone, 5-fluorouracil (5-FU) and leucovorin chemotherapy regimen in metastatic breast cancer. 8 patients received mitoxantrone 10 mg/m2 on day 1, leucovorin 200 mg/m2 and 5-FU 300 mg/m2 on days 1-5 by intravenous bolus every 28 days in a pilot study. Grades 3-4 granulocytopenia followed 55% of the courses, with 2 patients admitted for febrile neutropenia. Only a 29% objective response rate was seen in a subsequent phase II trial using reduced mitoxantrone doses. Comparison with other trials suggested that 5-day bolus 5-FU administration adversely affects the combination's therapeutic index.

Adenocarcinoma↗
PubMed1994

Instruction in surgical anatomy for gynecology residents using prosected human cadavers.

Prosected human cadavers were used by a team of anatomists and gynecologic surgeons to teach surgical anatomy to gynecology residents. The course was offered at the start of each 8-week gynecologic surgery rotation. Hemisections and other similar prosections were used to demonstrate anatomic relationships and surgical procedures from vantage points unobtainable at the operating table. The initial response from the faculty and residents was encouraging. The residents believed the program to be beneficial and were satisfied with it. Both the anatomy faculty and the gynecology faculty found new insights into teaching issues during the interdisciplinary process of course preparation and teaching.

Anatomy↗
PubMed1994

Hepatitis C virus-associated glomerulonephritis. Effect of alpha-interferon therapy.

Hepatitis C virus (HCV) infection may present as a primary glomerular disease. We report 34 adult patients who presented with proteinuria and had circulating anti-HCV antibodies. Primary risk factors included a history of intravenous drug abuse (56%) or blood transfusion (18%). Patients presented with nephrotic syndrome (71%) or with non-nephrotic proteinuria (29%) and had membranoproliferative or acute proliferative glomerulonephritis on renal biopsy. Signs of clinical liver disease were infrequent (18%), though elevated liver function tests were common (66%) and liver biopsy in 16 of 18 patients showed chronic active hepatitis. Cryoglobulinemia was frequent (59%), but only 44% had extrarenal manifestations. In 100% of cases tested, HCV RNA could be found in the serum or cryoprecipitates. Fourteen patients received interferon alpha for 6 to 12 months with a significant reduction in proteinuria but no improvement in renal function. A good clinical response correlated with disappearance of HCV RNA from the serum during treatment; however, relapse of viremia and renal disease was common after completing therapy. Evidence for HCV infection should be sought in all patients with primary glomerular disease. The optimal treatment strategy, however, remains to be defined.

Adult↗
PubMed1994

Disordered peripheral nerve conduction in DOOR(S) syndrome.

A case of DOOR(S) syndrome is detailed and the neurophysiological abnormalities observed in this patient and in other cases with this rare but recognisable autosomal recessive condition are considered. Particular emphasis is paid to the abnormal peripheral nerve conduction, which has not previously been recorded in the condition.

Brain↗
PubMed1994

Measuring the body composition of elderly subjects: a comparison of methods.

There is a paucity of data on differences between methods for the assessment of body composition in elderly subjects. Studies on younger adults suggest that such differences are of some practical significance at the individual level. In the present study the following methods of estimating percentage body fatness (BF%) were compared in healthy elderly men and women (mean age 70 (SD 6) years: densitometry; skinfold thickness; total body water; bioelectrical impedance (BIA) using an age-specific predictive equation and the manufacturers' equation; body mass index (BMI). Though BF% estimates from the various methods tended to be highly correlated with those from densitometry and with each other, differences between methods at the individual level were marked. In particular, the age-specific equations based on BMI and BIA systematically overestimated BF% relative to the other methods. Biases between BF% estimates derived from densitometry, skinfolds, BIA (manufacturers' equation) and total body water were less marked, indicating little evidence of systematic differences between these methods in elderly subjects. Individual differences between methods were slightly greater than those reported in some studies of younger adults, but this may be of little practical significance, and may be considered inevitable in view of variability between and within subjects in the extent to which the underlying assumptions of these two-component methods are met in elderly subjects.

Aged↗
PubMed1994

Statistical evaluation of relationships between analgesic dose and ordered ratings of pain relief over an eight-hour period.

Statistical considerations are discussed for the application of alternative methods to a clinical trial involving repeated ordinal ratings and multiple dosage levels of active drugs. Analyses included summary measures traditionally employed in studies of acute pain: sum of pain intensity differences from baseline, total pain relief, and total pain half gone. Estimators and confidence intervals of relative potency are developed for univariate and multivariate situations, using weighted least squares analysis with mean response and variances from Taylor series linearizations. The estimates from these methods are compared to those from traditional methods, such as ordinary least squares regression and Fieller's method for confidence intervals, as well as those from more recent developments, such as generalized estimating equations and sample survey data regression. A double-blind, two-center, randomized clinical trial of acute pain relief comparing placebo with two analgesics, each at two dosage levels, over an 8-hr period serves as an illustrative example for these techniques and comparisons.

Adolescent↗
PubMed1994

Assessment of hepatitis C virus RNA levels by quantitative competitive RNA polymerase chain reaction: high-titer viremia correlates with advanced stage of disease.

A quantitative competitive RNA polymerase chain reaction (QC-PCR) assay was developed for measuring absolute levels of hepatitis C virus (HCV) RNA in the sera of 121 viremic persons, including 64 asymptomatic blood donors, 39 symptomatic patients referred for treatment of chronic hepatitis C, and 18 patients with end-stage liver disease referred for liver transplantation. Mean HCV RNA levels (log molecules per milliliter) were lowest among blood donors with normal alanine aminotransferase (ALT) values (5.8 +/- 1.5), higher among blood donors with elevated ALT (6.9 +/- 0.8) and clinic patients with chronic active hepatitis (6.9 +/- 0.7), and highest among patients with cirrhosis (7.1 +/- 0.8) or end-stage liver disease (7.6 +/- 1.0). High-titer viremia ( > or = 7.5 logs/mL) was more frequent among patients with end-stage liver disease (14/18; 78%) than either blood donors (10/64; P < .001) or patients with chronic active hepatitis (7/26; P < .001). Thus, 121 (94.5%) of 128 anti-HCV-positive persons were viremic. QC-PCR may be valuable for monitoring HCV infection status and selecting individuals for therapy.

Base Sequence↗
PubMed1994

Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients.

Epstein-Barr virus (EBV) infection is recognized as the principal aetiological factor in the pathogenesis of post-transplant lymphoproliferative disease (PTLD), particularly when primary EBV infection occurs after transplantation. We analysed, using a time-dependent proportional hazards model, the factors associated with development of PTLD in 40 adult liver transplant recipients who were seronegative for EBV prior to transplantation. Of 40 patients, 13 (33%) had a tissue diagnosis of PTLD at a median time of 126 days after transplantation. The multivariate analysis showed that prior CMV disease, the number of steroid boluses given and the number of units of RBC and FFP transfused were significant risk factors for development of PTLD.

Adult↗
PubMed1994

Immunoglobulin G antibody responses to polyvalent pneumococcal vaccine in children in the highlands of Papua New Guinea.

The immunoglobulin G (IgG) antibody responses to a pneumococcal polysaccharide vaccine were examined for 480 children aged 3 months to 5 years and living in Tari, Southern Highlands Province, Papua New Guinea. Antipneumococcal IgG to the seven serotypes most frequently causing invasive disease (types 2, 5, 6B, 7F, 14, 19F, and 23F) was measured by an enzyme-linked immunosorbent assay in serum collected before vaccination and 1 and 6 months after vaccination. Prevaccination antibody levels fell rapidly after 3 months of age and remained low throughout the first 2 years of life. One month after vaccination, geometric mean titers of antipneumococcal IgG to serotypes 2, 7F, 23F, and 5 were at least twice those of antibodies in nonvaccinated children of the same age from the ages of 5, 6, 9, and 12 months onwards, respectively; postvaccination antibody responses to serotypes 6B, 14, and 19F rose gradually during the second year of life. Elevated antibody titers to serotypes 2 and 7F were maintained 6 months after vaccination. Thus, young Papua New Guinean children are capable of mounting a good immune response to some pneumococcal capsular polysaccharides from a young age, and the antibody responses to capsular polysaccharides are consistent with studies in developed countries. However, in Papua New Guinea, the serogroup distribution of invasive disease matches the immunogenic components of the pneumococcal polysaccharide vaccine more closely than in developed countries, a fact which helps to explain the results of controlled trials in Papua New Guinea, in which this vaccine prevented death and severe morbidity from pneumonia in young children.

Age Factors↗
PubMed1994

Reciprocal regulation of the Epstein-Barr virus BamHI-F promoter by EBNA-1 and an E2F transcription factor.

The Epstein-Barr virus BamHI-F promoter (Fp) is one of three used to transcribe the EBNA latency proteins, in particular, EBNA-1, the only viral gene product needed for episomal replication. Fp is distinguished by possession of the only EBNA-1 binding sites (the Q locus) in the Epstein-Barr virus genome outside oriP. Activity of Fp is negatively autoregulated by interaction of EBNA-1 at two sites in the Q locus, which is situated downstream of the RNA start site. We demonstrate in transient assays that this EBNA-1-mediated repression of Fp can be overcome by an E2F transcription factor which interacts with the DNA at a site centered between the two EBNA-1 binding sites within the Q locus. An E2F-1 fusion protein protects the sequence 5'-GGATGGCGGGTAATA-3' from DNase I digestion, and a DNA probe containing this sequence binds an E2F-specific protein complex from cell extracts, although this region is only loosely homologous with known consensus binding sites for E2F transcription factors. In mobility shift assays, E2F can displace the binding of EBNA-1 from the Q locus but not from oriP, where the E2F binding site is not present. E2F also activates expression of Fp in epithelial cells. These findings identify a potentially new binding site for members of the E2F family of transcription factors and suggest that such a factor is important for expression of EBNA-1 in lymphoid and epithelial cells by displacing EBNA-1 from the Q locus. In addition, the possibility that Fp activity is under cell cycle control is raised. Since the supply of functional E2F varies during the cell cycle and since in these assays overexpression of E2F can overcome repression of Fp by EBNA-1, control of transcription of EBNA-1 mRNA by cell cycle regulatory factors may help to bring about ordered replication of episomes.

Antigens, Viral↗
PubMed1994

Validation of the sensormedics (S2900Z) metabolic cart for pediatric exercise testing.

The accuracy of many microprocessor controlled exercise testing systems has not been established, particularly for testing children. A metabolic cart (Sensormedics S2900Z) was validated against a reference system (Douglas bag) in children. The systems were tested using 10 active, healthy children (age 11.6 +/- 2.3 yrs) during physiological steady state at two exercise intensities, submaximal walking and running. Eight children performed a high ventilatory flow (HVF) protocol, running for 11 min. All 10 performed a low ventilatory flow (LVF) protocol, walking for 11 min. In both, gas samples were measured after 6 to 7 and 10 to 11 min into the Douglas bag, and after 8 to 9 min by the test system. There was minimal evidence of bias for VO2 at either ventilation rate. Greater variability was noted for FeCO2 and VCO2. In conclusion, the Sensormedics S2900Z appears to be adequate for testing children.

Bias↗
PubMed1994

Na(+)-coupled alanine transport in LLC-PK1 cells.

Transport of alanine (Ala) was characterized in LLC-PK1 renal epithelial cells. Transport capability for Ala falls by 75% in postconfluent cultures, while Na(+)-coupled alpha-methylglucoside (AMG) transport rises more than fourfold during the same interval. The kinetics of Ala transport were characterized in ATP-depleted cells to allow experimental imposition of changes in Na+ gradient and control of membrane potential across the plasma membrane. At 100 microM Ala and 135 mM Na+, > 98% of the unidirectional Ala influx is dependent on the presence of Na+ in cells from postconfluent cultures. Li+ is only 1% as effective as Na+, and other monovalent cations are ineffective in supporting Ala uptake. alpha-(Methylamino)isobutyric acid (MeAIB; 5 mM) causes only a small inhibition (approximately 10%) of 100 microM Ala influx. The low selectivity for Li+; low sensitivity to competition by MeAIB or aminoisobutyric acid; pronounced inhibition by serine, homoserine, cysteine, homocysteine and threonine; moderate inhibition by valine, isoleucine, proline and histidine; and lack of inhibition by lysine, arginine, and aspartate are more consistent with those characteristics reported for entry via the ASC amino acid transport system rather than those associated with the A system. Alanine influx exhibits a hyperbolic relationship with increasing Ala or Na+ concentration. Kinetic analysis suggests a single transport pathway with a Michaelis constant (Km) for alanine of 380 microM (when Na+ is 135 mM), apparent Km for Na+ of 32 mM (with 100 microM Ala), and a maximum velocity of 7 nmol.min-1.mg cell protein-1. An interior-negative diffusion potential induces a similar enhancement of [14C]alanine or [14C]tetraphenylphosphonium influx (approximately 40%). In contrast, AMG influx is enhanced by a factor of 2.2 under the same conditions. AMG uptake also shows a sigmoidal relationship with Na+ concentration. Hill coefficients are 1.56 for AMG and 1.0 for alanine. Direct measurement of Na(+)-Ala coupling stoichiometry yields a value of 1.01 +/- 0.07. Under the same conditions, Na(+)-AMG coupling stoichiometry is 2.1 +/- 0.25. The difference in coupling stoichiometries provides an explanation for differences in intensity of interaction between Na(+)-coupled transport systems for sugars and amino acids.

Alanine↗
PubMed1994

Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability.

The efficacy and tolerability of O-(beta-hydroxyethyl)-rutosides (HR) in elderly patients (aged over 65 years) with chronic venous insufficiency or varicose veins was studied in a multicentre, double-blind, randomised, placebo-controlled trial. Of the 104 patients entered into the trial, data from 102 were available for analysis of tolerability and from 86 for efficacy. Treatment was for 6 months, with monthly examinations. Three different dosages were used due to slight differences in the registered dosage in various countries: (1) 250 mg 4 times daily (1 g/day), UK, n = 19 patients; (2) 300 mg 3 times daily (900 mg/day), FRG and Belgium, n = 55, and (3) 300 mg 4 times daily (1,200 mg/day), The Netherlands, n = 30. Each centre had its own placebo control group. The HR-treated group (n = 41) showed a significantly greater reduction in the total symptom score, 5.7 +/- 2.4 to 2.3 +/- 1.8, than in the placebo group, 4.4 +/- 3.0 to 3.0 +/- 2.4 (p < 0.01). Of the 5 studied symptoms there was also a significant (p < 0.05) improvement in leg cramps, heavy legs and restless legs. No significant differences between the two groups were seen for aching pains and paraesthesia. A small reduction was also seen in ankle and calf circumferences, which became significant at the end of the trial (p < 0.05). Pitting oedema of the leg (p < 0.01) and eczema of the leg (p < 0.05) also improved significantly greater than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Outcome of the treatment for sarcoidosis.

The clinical characteristics and pathology of sarcoidosis are well defined; however, the optimal therapy for this disorder remains unclear. Although patients respond, acutely, to corticosteroid therapy, it is not clear that these agents ultimately alter the natural history of this disease. These observations and that corticosteroids have significant side effects suggest that only patients who will clearly benefit from corticosteroid therapy should be treated. In a prospective study of patients' with sarcoidosis (n = 98), we limited our use of corticosteroids to those patients who had objective evidence of recent deterioration in lung function or serious extrapulmonary disease. All patients with sarcoidosis fulfilling these criteria were treated with corticosteroids. Patients were tapered off corticosteroids after they were treated for 1 yr. Of the 98 study subjects, 91 had not received therapy for the disease and 7 were on therapy before entry into the study. Of the 91 previously untreated patients, 55 were observed without therapy and 36 were treated with corticosteroids. Of those who were observed off therapy, only eight deteriorated. Of these latter patients, six responded and stabilized with the administration of corticosteroids for treatment of the underlying disease, to antibiotics for an associated bronchiectasis, or to diuretics for treatment for congestive heart failure; two were lost to follow-up. None of these six patients deteriorated while receiving corticosteroids. Of the 36 patients who deteriorated and were treated with corticosteroids, 20 remained stable and 16 improved clinically. Of the 37 patients who were eventually tapered off corticosteroids, five deteriorated and required reinitiation of corticosteroid therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer.

PURPOSE: This phase II study was designed to assess the effects of mitoxantrone with prednisone in patients with metastatic prostate cancer who had progressed on hormonal therapy. The methods of assessment included quality-of-life analyses, pain indices, analgesic scores, and the National Prostatic Cancer Project (NPCP) criteria. PATIENTS AND METHODS: Patients received mitoxantrone 12 mg/m2 intravenously every 3 weeks plus prednisone 10 mg orally daily. All had a castrate serum testosterone and Eastern Cooperation Oncology Group (ECOG) performance status < or = 3, and had not received prior chemotherapy. Every 3 weeks, analgesic intake was scored, and a present pain intensity (PPI) record and visual analog scale (VAS) describing pain were collected. Every 6 weeks, the European Organization for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire plus a prostate-specific module were completed. A palliative response was defined as a decrease in analgesic score by > or = 50% or a decrease in PPI by > or = two integers without any increase in the other. RESULTS: Twenty-seven patients were entered onto the study. Nine of 25 (36%) assessable patients achieved a palliative response maintained for > or = two cycles (range, two to eight or more). Improvements in mean PPI and VAS pain scores after each cycle of therapy (P < .05) were seen. Quality-of-life analysis showed improvements in social and emotional functioning, and in pain and anorexia. Using NPCP criteria, one patient achieved a partial response (PR) and 12 had stable disease; one of seven patients with measurable disease had a PR. No serious nonhematologic toxicity was experienced, and there were no episodes of febrile neutropenia. CONCLUSION: Mitoxantrone with low-dose prednisone is a well-tolerated treatment regimen that has some beneficial effects on disease-related symptoms and quality of life for patients with advanced prostate cancer.

Aged↗
PubMed1994

Empathy and adolescent male sex-offenders.

This study provides data on empathy for 82 adolescent male sex-offenders and 108 male nonoffenders. No statistically significant association was found between scores on a 4-item measure of empathy and sex-offender status.

Adolescent↗