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Biomedical subjects

J J Ryan

Publications and source records attributed to J J Ryan.

At least 19 recordsLinked to original sources

Unusual combinations of verbal and performance IQs in normal and neurologically impaired elderly.

For the WAIS-R old age standardization sample, unusual Verbal-Performance IQ combinations were generated at the .05 and .01 levels of significance. In a preliminary attempt to determine the neurological significance of these unusual test score combinations, the standardization based values were compared to those of a small sample of elderly brain-injured subjects. The frequency of unusual IQ combinations was essentially the same for the normal and brain-damaged elderly. Unusual VIQ-PIQ combinations should not be considered pathognomonic of neurological impairment.

Aged

Human mesangial cells synthesize interleukin 1 alpha but not interleukin 1 beta, interleukin 1 receptor antagonist, or tumour necrosis factor.

There is controversy over whether mesangial cells synthesize and release IL-1 and TNF, and many of the positive experiments were performed before specific reagents and molecular probes were available. Consequently we have stimulated human mesangial cells using protocols known to stimulate the synthesis of other cytokines. No mRNA for IL-1 beta or TNF could be detected in quiescent or proliferating mesangial cells irrespective of whether they had been exposed to cytokines or not. In contrast mRNA for IL-1 alpha was detected in cells stimulated with IL-1 beta 10 ng/ml or with TNF 500 ng/ml; IL-1 alpha was also detected in cell lysates from stimulated mesangial cells. We could not detect mRNA for IL-1 receptor antagonist in any of the cell preparations. These results suggest that mesangial cells are unlikely to be a major source of IL-1 beta or TNF.

Cells, Cultured

Persistent brominated and chlorinated dioxin blood levels in a chemist. 35 years after dioxin exposure.

This is the first report on occupational health hazards to dioxin chemists associated with laboratory exposure to 2,3,7,8-tetrabromodibenzodioxin (TBrDD), and further characterizes the human response to 2,3,7,8 tetrachlorodibenzodioxin (TCDD). In this case study the chemist was exposed on two separate occasions. In March 1956, after synthesizing 10 g of TBrDD, the chemist suffered from mild and transient chloracne of the neck and wrists; in September 1956, after synthesizing 16 g of TCDD, he suffered severe chloracne of the entire body, headaches, backache, and leg pain on exertion. His measured 2,3,7,8-TBrDD in 1991 was 625 parts per trillion (ppt) in whole blood lipid, 35 years after initial exposure and 18 ppt TCDD, an elevated level in comparison with the mean 2,3,7,8-TCDD level of 5 ppt in the US population. This is the first reported detection of a brominated dioxin in human tissue. The total halogenated dioxin body burden in September 1956 is estimated to have been between 13,005 ppt and 146,726 ppt. This amount can be considered to be, at least in this person, a strong chloracnegenic dose, and a dose causing human nervous system and muscular or circulatory system responses. This uptake demonstrates an occupational hazard to chemists and chemical workers, and the usefulness of human tissue dioxin measurements to document absorption.

Adult

Factor analysis of the Chinese WAIS with persons who have mental retardation.

The Chinese revision of the WAIS (designated WAIS-RC) was factor analyzed for a sample of individuals with mental retardation. There were 55 Chinese subjects with a mean Full Scale IQ of 49.13 (SD = 16.46). Results indicated that a two-factor solution comprised of the familiar Verbal Comprehension and Perceptual Organization factors best described the data. Comparison of the Chinese structure with that of a low-IQ Canadian sample tested with the American WAIS-R revealed congruence coefficients of .97 and .98 for Verbal Comprehension and Perceptual Organization, respectively. These findings provide support for further cross-cultural research utilizing the latest editions of the American and Chinese Wechsler scales.

Adolescent

c-myb effects on kinetic events during MEL cell differentiation.

During dimethylsulfoxide (DMSO)-induced differentiation of Friend mouse erythroleukemia (MEL) cells there is a biphasic fall in c-myb mRNA levels. We have previously shown that constitutive expression of c-myb blocks differentiation. To delineate more accurately the point at which Myb blocks differentiation, MEL cells were transfected with a human c-myb construct under the control of the beta-globin promoter and enhancers. In concert with endogenous DMSO-induced globin transcription during MEL cell differentiation, the beta-globin c-myb transcription unit of the transfected plasmid is activated after 3-5 days of culture in media containing DMSO. Here we describe c-myb-transformed MEL clones which undergo delayed expression of the exogenous c-myb following 3-5 days of culture in DMSO. In contrast to wild-type MEL cells, both clones failed to display phenotypic markers of differentiation and continued to proliferate for up to 10 days of culture. These data suggest that the late fall in c-myb levels may be required in order for differentiation to occur. Additionally, we suggest that constitutive expression of c-myb does not block early commitment events such as activation of histone Hl', subsequent chromatin condensation, and alteration of proliferation-related gene expression. Taken together, these results show that c-myb acts very late in the process of differentiation.

Animals

Allostimulatory analysis of a newly-defined and widely-distributed Mls superantigen.

We previously noted that Mlsa,c C58/J responder cells proliferated unexpectedly to H-2k-compatible Mlsa or Mlsc prototypic stimulator cells in a primary mixed lymphocyte reaction. The present investigation was performed to evaluate whether the response of C58/J T cells to these H-2- and Mls-compatible stimulator cells could functionally identify a newly-defined member of the Mls superantigen family through its allostimulatory ability. We observed that C58/J responder cells also proliferated when cultured with H-2-compatible prototypic Mls(null), Mlsb (nonstimulatory), or Mlsa,c splenic stimulator cells. The widely distributed nature of the non-MHC ligand recognized by C58/J T cells is indicated by the finding that 11 of 12 H-2k inbred mouse strains clearly expressed this specificity. A gradient of stimulatory capacity from low to high across this newly-defined non-MHC difference was detected with splenocytes from these different inbred mouse strains. The Mls(a,c) genetic composition of C58/J was confirmed by the observation that crossing C58/J with parental B10.BR (responsive to both Mlsa and Mlsc determinants) generated F1 progeny that were unresponsive to H-2k-compatible Mlsa, Mlsc, or Mls(a,c) stimulator cells. Like prototypic Mlsa and Mlsc, the non-MHC specificity recognized by C58/J responder cells, termed Mlsf, was particularly sensitive to radiation (versus mitomycin C) treatment of the stimulator cells, was greatly augmented after anti-IgD activation of splenic stimulator cells, was blocked with anti-MHC class II antibody, and was effectively presented by phenotypically normal female but not B cell-defective xid+ male CBA/N F1 stimulator cells.

Animals

Interleukin-1 beta stimulates human mesangial cells to synthesize and release interleukins-6 and -8.

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) have been reported to stimulate human mesangial cells (HMC) to proliferate and synthesize eicosanoids. We have examined whether they also induce HMC to release cytokines. In this study we show that both IL-1 and TNF stimulate HMC to release IL-6 and IL-8. Cycling and quiescent HMC were stimulated with various concentrations of either recombinant IL-1 beta or TNF for 1 to 24 hours. IL-1 beta at doses as low as 6 pg/ml stimulated mesangial cells to synthesize mRNA for both IL-6 and IL-8 as assessed by Northern analysis; mRNA for tubulin remained constant, which demonstrated a specific increase in mRNA. Secretion of IL-6 and IL-8 into the culture medium increased (4.5 to 18 ng/ml and 4 to 40 ng/ml, respectively) measured by ELISAs. TNF had similar effects but only in high concentrations (greater than 100 ng/ml). IL-1 beta did not stimulate cells to proliferate, as measured by 3H thymidine incorporation. TNF caused proliferation but only in concentrations over 100 ng/ml. We conclude that IL-1 beta is a potent stimulator of human mesangial cell production of IL-6 and IL-8, both of which may influence injury in nephritis. TNF also stimulates mesangial cells but only in pharmacological doses.

Cells, Cultured

Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) have been identified as a diagnostic marker in primary systemic vasculitis, and immunofluorescence assays identify two patterns of binding: cytoplasmic (C-ANCA and perinuclear (P-ANCA). We have examined retrospectively the use of such assays in long-term monitoring of disease activity, in order to determine the relationship between presence of ANCA and relapse, and to assess their suitability as a guide to therapy. Seventy patients were studied over a period of 50 months, using clinical and laboratory criteria for the diagnosis of relapse and the internationally standardised immunofluorescence assay for detection of ANCA. In 19 patients C- or P-ANCA were detectable throughout the study period; six of these (with C-ANCA) relapsed. In 18 patients ANCA were undetectable during long-term follow-up; none of these patients relapsed. In 33 patients C- or P-ANCA were intermittently present; nine of these relapsed and all had C-ANCA detectable at the time of relapse. In six of the nine cases, relapse was accompanied or closely preceded by reappearance of C-ANCA. We conclude that continuing presence and reappearance of ANCA may identify patients who are at risk of relapse and who are most likely to benefit from long-term immunosuppressive therapy.

Antibodies, Antineutrophil Cytoplasmic

Principal components analysis of the Psychological Screening Inventory in a sample of substance abusers.

A principal components analysis of responses to the Psychological Screening Inventory from a sample of substance abusers was conducted. Subjects were 153 inpatients admitted to a midwestern program for chemical dependency treatment. Means for age and education were 28.0 yr. (SD = 8.1) and 11.4 (SD = 1.8), respectively. Analysis indicated that a two-factor solution best described these data. Factor 1 reflected over-all maladjustment, while Factor 2 was a measure of extroversion. Clinical utility of the inventory was discussed.

Adult

Novel application of proton nuclear magnetic resonance spectroscopy in the identification of 2'-chloronordiazepam metabolites in the dog.

The only metabolite of 2'-chloronordiazepam, 7-chloro-1,3-dihydro-5-(2'-chlorophenyl)-2H-1,4-benzodiazepin-2-one (1), previously identified in the dog is lorazepam (2), which is a product of 3-hydroxylation. Two phenolic metabolites (3 and 4) in the dog corresponding to 4'-hydroxylation of the 5-phenyl ring and 9-hydroxylation of the fused benzene ring, respectively, have now been identified. The structure of the 9-hydroxy isomer 4 is deduced simply from the observed NMR spectral AB (J meta = 2.5 Hz) pattern of the protons of the fused benzene ring. In contrast, since a 2'-chloro substituent is present on the 5-phenyl ring of the parent drug, the usual method of recognizing 4'-hydroxylation of this ring by observation of AA'BB' multiplets in the proton nuclear magnetic resonance (1H NMR) spectra is inapplicable. Hence, a novel method is introduced to identify the 4'-hydroxy isomer 3, based on attributing different sets of NMR substituent effect parameters to hydroxyl groups, depending on whether these groups are meta or para to the benzodiazepinimine function. The urinary plus fecal excretion of 2-4 by one dog given in a single oral 10 mg/kg dose of 14C-labeled 1 amounted to 20, 5, and 7% of the dose, respectively; the urinary metabolites were excreted predominantly as conjugates of glucuronic acid and/or sulfate.

Animals