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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 217 records · Page 12Linked to original sources
PubMed1995

Adsorption of botulinum toxin to activated charcoal with a mouse bioassay.

STUDY OBJECTIVE: We evaluated the effectiveness of activated charcoal (AC) in adsorbing Clostridium botulinum type A toxin using a mouse bioassay. DESIGN: Prospective, blinded, randomized, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: One hundred forty Swiss/Webster ND-4 strain mice. INTERVENTION: Food contaminated with type A botulinum toxin was homogenized in a phosphate/gel buffer (pH 6.2). The concentrate was diluted by factors of 1:10, 1:50, and 1:100. AC was added to aliquots of the dilutions to a 20% final concentration. The samples were centrifuged, supernatant was removed, and separate groups of mice were injected intraperitoneally with .5 mL of each dilution (those treated with AC and controls untreated with AC). The animals were then observed over 5 days for signs of botulism. RESULTS: None of the 60 animals injected intraperitoneally with dilutions treated with AC was observed to have any signs of botulism. In contrast, deaths were observed in 10 of 20, 9 of 20 and 4 of 20 mice injected with untreated dilutions of 1:100, 1:50, and 1:10, respectively (P < .004). CONCLUSION: In this model, treatment of botulinum toxin with AC before administration resulted in greatly reduced morbidity and mortality.

Adsorption↗
PubMed1995

Comparison of simulated and in-vivo plasma levels of cilastatin following intravenous in-line drug administration.

The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.

Animals↗
PubMed1995

Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis.

Psoriasis is a hyperproliferative and inflammatory skin disorder of unknown aetiology. A fusion protein composed of human interleukin-2 and fragments of diphtheria toxin (DAB389IL-2), which selectively blocks the growth of activated lymphocytes but not keratinocytes, was administered systemically to ten patients to gauge the contribution of activated T cells to the disease. Four patients showed striking clinical improvement and four moderate improvement, after two cycle of low dose IL-2-toxin. The reversal of several molecular markers of epidermal dysfunction was associated with a marked reduction in intraepidermal CD3+ and CD8+ T cells, suggesting a primary immunological basis for this widespread disorder.

Adult↗
PubMed1995

How should zoster trials be conducted?

In 1994, an international group of interested clinicians and biostatisticians met to discuss the design of clinical trials in herpes zoster. They agreed that trials in herpes zoster should have prospectively agreed definitions of all outcome measures and plans for data analysis. In immunocompetent individuals, in whom pain is the major outcome measure, trials should only include patients over the age of 50 years, and for those recruited within 72 h of rash onset, should be designed to demonstrate superiority of any new therapy over existing antivirals. The primary endpoint should be time to cessation of pain for at least 4 weeks and, for the purposes of statistical analysis of its duration, the pain associated with herpes zoster ought to be considered as a continuum. All other variables, including the incidence of post-herpetic neuralgia and effects upon quality of life should be considered as secondary end-points. Evaluation of treatment effects on primary endpoints should be based upon an intent-to-treat (ITT) analysis and subgroup analysis should be used only to support the findings of the ITT analysis. These elements of good study design should be borne in mind in the evaluation of current and future trails of antiviral drugs in herpes zoster.

Clinical Trials as Topic↗
PubMed1995

An analysis of interobserver reliability and representativeness of data from the Veterans Affairs Cooperative Study on Processes, Structures, and Outcomes in Cardiac Surgery.

The authors made some preliminary judgments regarding the reliability and representativeness of the data in the early stages of the Veterans Affairs Cooperative Study entitled Processes, Structures, and Outcomes of Care in Cardiac Surgery (PSOCS). Preliminary PSOCS interobserver reliability and potential patient and site selection bias reported were based on comparisons with identical risk, procedure, and outcome data items collected independently in the Continuous Improvement in Cardiac Surgery Study. PSOCS interobserver reliability for this limited set of variables was good to excellent. At the six pilot centers, there were few important differences between patients entered into PSOCS and those not entered. The 14 Veterans Affairs medical centers that will participate in the full-scale PSOCS study and the 29 nonparticipating centers exhibited similar patient populations. will be valuable.

Cardiac Surgical Procedures↗
PubMed1995

Working memory and preparation elicit different patterns of slow wave event-related brain potentials.

Some event-related brain potential (ERP) studies of working memory have used delayed match-to-sample designs in which a stimulus (S1) is held in memory for comparison with a subsequent stimulus (S2). During the S1-S2 interval, ERP slow negatives varied with both the type and amount of material held in working memory. One interpretation is that these slow waves index working memory operations. An alternative explanation is that they only reflect general preparatory processing for the response to S2. To decide between these explanations, we used two visual processing tasks that required similar preparation for S2. In one task, visual memory rehearsal operations were required. During the S1-S2 interval, there were clear differences between the amplitudes, topographies, and the effect of information load on the slow waves in two tasks, thus ruling out preparation only as an explanation.

Adult↗
PubMed1995

Isolation and characterization of a novel mitogenic regulatory gene, 322, which is transcriptionally suppressed in cells transformed by src and ras.

In an attempt to isolate novel regulatory and/or tumor suppressor genes, we identified cDNAs whose abundance is low in NIH 3T3 cells and further decreased following the expression of the activated oncogene, v-src. The transcription of one such gene, 322, is suppressed at least 15-fold in src-, ras-, and fos-transformed cells and 3-fold in myc-transformed cells but is unaffected in raf-, mos-, or neu-transformed cells. Activation of a ts-v-src allele in confluent 3Y1 fibroblasts resulted in an initial increase in 322 mRNA levels after 1 to 2 h followed by a rapid decrease to suppressed levels after 4 to 8 h. Morphological transformation was not detected until 12 h later, indicating that the accumulation of 322 transcripts is regulated by v-src and not as a consequence of transformation. Addition of fetal calf serum to starved subconfluent NIH 3T3 or 3Y1 fibroblasts resulted in a similar biphasic regulation of 322, indicating that 322 transcription is responsive to mitogenic factors. Sequence analysis of a putative full-length 322 cDNA clone (5.4 kb) identified a large open reading frame (ORF) encoding a 148.1-kDa product. In vitro transcription and translation of the 322 cDNA from a T7 promoter resulted in a 207-kDa product whose electrophoretic mobility on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel was unaffected by digestion with endoglycosidase F. The discrepancy in predicted versus measured molecular weights may result from the high percentage of acidic residues (roughly 20% Glu or Asp) in the 322 ORF product. Comparison of the 322 cDNA ORF with sequences in data banks indicates that this gene is novel. The 322 ORF product contains a potential Cys-1-His-3 Zn finger, at least five nuclear localization signals of the adenovirus E1a motif K(R/K)X(R/K), and alternating acidic and basic domains. Overexpression of the 322 cells resulted in the selection of rapidly growing cells which had lost the transduced 322 cDNA. Thus, 322 represent a novel src- and ras-regulated gene which encodes a potential regulator of mitogenesis and/or tumor suppressor.

3T3 Cells↗
PubMed1995

Energy expenditure in children of lean and obese parents.

We evaluated whether children of obese parents have defects in energy expenditure in a study of 73 children (5 +/- 0.9 yr of age) of lean and obese parents. Total energy expenditure (TEE) was measured over 14 days by use of doubly labeled water and physical activity energy expenditure (AEE) derived by subtracting resting energy expenditure (REE) under postprandial conditions. Fat and fat-free mass (FFM) were measured in children and parents with use of bioelectrical resistance. There were no significant correlations between TEE, REE, or AEE in children (after adjustment for FFM) and body fat in children or body fat in mothers or fathers. In three-way analysis of covariance (ANCOVA, with FFM as a covariate), there were no significant effects of gender in children, obesity in mothers, or obesity in fathers on TEE or AEE in children. There was a significant effect of gender and a significant interaction between obesity in mothers and obesity in fathers on REE; relative to children with two nonobese or two obese parents, REE was approximately 6% lower in children when mothers only or fathers only were obese. In conclusion, our data do not support the hypothesis that children of obese parents have major defects in energy expenditure.

Adult↗
PubMed1995

Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy.

We investigated the mechanisms of alphafetoprotein (AFP) transfer across the human placenta by correlating measurements of AFP transfer with cytochemical localization of AFP. Placental cotyledons were dually perfused in vitro with either the fetal or maternal perfusate containing umbilical cord plasma as a source of AFP. Steady state AFP clearance, corrected for release of endogenous AFP, was 0.973 +/- 0.292 microliter/min per gram in the fetal to maternal direction (n = 10), significantly higher (P < 0.02) than that in the maternal to fetal direction (n = 5; 0.022 +/- 0.013 microliter/min per gram). Clearance of a similarly sized protein, horseradish peroxidase was also asymmetric but clearance of the small tracer creatinine was not. Using a monoclonal antibody, we localized AFP to fibrinoid deposits in regions of villi with discontinuities of the syncytiotrophoblast, to cytotrophoblast cells in these deposits, to syncytiotrophoblast on some villi, and to trophoblast cells in the decidua. We conclude that AFP transfer in the placenta is asymmetric and that there are two available pathways for AFP transfer: (a) from the fetal circulation into the villous core and across fibrinoid deposits at discontinuities in the villous syncytiotrophoblast to enter the maternal circulation; and (b) AFP present in the decidua could enter vessels that traverse the basal plate.

Biological Transport↗
PubMed1995

Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate.

The authors investigated the effects of a nontoxic differentiation inducer, phenylacetate (PA), on neuroectodermal tumor-derived cell lines. Treatment of medulloblastoma (Daoy and D283 MED) and glioma (U-251MG, C6, and RG2) cell lines resulted in a dose-dependent decline in DNA synthesis and cell proliferation, associated with accumulation in the G0/G1 phase of the cell cycle. Phenylacetate decreased transforming growth factor (TGF)-beta 2 production by medulloblastoma Daoy cells. Neutralizing antibodies against either TGF beta 2 or TGF beta 1 failed to block the growth arrest observed. This suggests that, unlike other differentiation agents, such as retinoic acid, the effect of PA on medulloblastoma proliferation is not mediated by a TGF beta pathway. In addition to cytostasis, PA induced marked morphological changes in U-251MG and C6 glioma cells associated with increased abundance of glial fibrillary acidic protein-positive processes. Although the morphology of PA-treated medulloblastoma cells was not significantly altered, the D283 MED cells exhibited increased expression of neurofilament proteins and Hu antigen, indicative of differentiation along a neuronal pathway. The effects of PA on the medulloblastoma cell lines were compared to its effects on the human neuroblastoma cell line BE(2)C, which is capable of a bidirectional differentiation toward a neuronal or a glial/schwann cell pathway. In BE(2)C cells, PA induced differentiation toward a schwann/glial cell-like phenotype, suggesting that the choice of differentiation pathway is cell type and agent specific. These in vitro antiproliferative and differentiation inducing effects of PA suggest that this agent warrants further evaluation as a potential therapeutic modality for the treatment of medulloblastoma and malignant glioma in humans.

Animals↗
PubMed1995

Energy expenditure and body fat distribution in Mohawk children.

OBJECTIVE: Epidemiologic studies suggest that Native Americans, including the Mohawk people, have a high prevalence of obesity, diabetes, and cardiovascular risk. However, current information on alterations in related variables such as energy metabolism and body composition in Native Americans is almost exclusively limited to already obese Pima adults living in the Southwest. The aim of this study was to characterize energy metabolism and body composition in young Mohawk children (17 girls, 11 boys; aged 4 to 7 years) as compared to Caucasian children (36 girls, 34 boys; aged 4 to 7 years). Total energy expenditure was measured by doubly labeled water, postprandial resting energy expenditure by indirect calorimetry, and activity energy expenditure was derived from the difference between total and resting energy expenditure. Fat and fat free mass were estimated from bioelectrical resistance, and body fat distribution was estimated from skinfolds and circumferences. RESULTS: There were no significant effects of ethnic background or sex on body weight, height, or body mass index. Fat free mass was significantly higher in boys and fat mass was significantly higher in girls, with no effect of ethnic background. Chest skinfold thickness, the ratio of trunk skinfolds:extremity skinfolds, and the waist:hip ratio were significantly higher in Mohawk children by 2.5 mm, 0.09 units, and 0.03 units, respectively, independent of sex and fat mass. Total energy expenditure was significantly higher in Mohawk children compared to Caucasian (100 kcal/day in girls, 150 kcal/day in boys), independent of fat free mass and sex, due to a significantly higher physical activity-related energy expenditure. CONCLUSION: These data suggest that: 1) body fat is more centrally distributed in Mohawk relative to Caucasian children, and this effect is independent of sex and body fat content; 2) Mohawk children have a greater total energy expenditure than Caucasian children, independent of fat free mass, due to greater physical activity-related energy expenditure.

Adipose Tissue↗
PubMed1995

Spontaneous resolution of retained renal calculi in USAF aviators.

USAF aviators may be granted medical waivers for continued flying duties when diagnosed as having retained renal calculi in parenchymal locations or in portions of the collecting system from which spontaneous passage is unlikely. The USAF Aircrew Medical Waiver File was reviewed in order to determine the proportion of USAF aviators with waivers for retained renal calculi whose calculi subsequently resolved. Of the 60 currently active aviators granted waivers between January 1976 and December 1990, 7 have had their retained calculi resolve following surgical intervention, and 13 (21.7%), 95% CI [11.2%, 32.1%], had "spontaneous" resolution of their retained calculi. Using the Armstrong Laboratory's Aeromedical Consultation Service clinical database, it was possible to determine how the diagnoses of retained stones were established and/or disestablished in 15 of the 60 aviators. Theories on stone formation and resolution, tools employed in diagnosis, and implications of these study findings on flight duties are discussed.

Aerospace Medicine↗