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Biomedical subjects

J J Ryan

Publications and source records attributed to J J Ryan.

At least 73 records · Page 4Linked to original sources

Exploratory factor analysis of the Wechsler Adult Intelligence Scale-Revised in a sample of brain-damaged women.

The first exploratory factor analysis of the WAIS-R using an exclusively female sample (N = 152) of brain-damaged patients was conducted. Means for age, education, and Full Scale IQ were 43.51 years(SD = 18.22), 12.60 years(SD = 2.47), and 86.34(SD = 13.32). Results indicated that either a two- or three-factor model was plausible for this sample. The two-factor solution supported Wechsler's (1981) Verbal and Performance IQ designations, while the three-factor model revealed Verbal-Comprehension (i.e., Information, Comprehension, Vocabulary, and Similarities), Perceptual-Organization (i.e., all Performance subtests), and Freedom From Distractibility (i.e., Digit Span) factors. Comparison of the factor structures for the present sample with those of normal women and brain-damaged men suggested factorial equivalency across groups.

Journal Article↗

Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells.

The Kit tyrosine kinase regulates growth and differentiation of many hematopoietic cells through a signal transduction process that remains to be fully elucidated. Kit has been shown to associate with the receptor for erythropoietin (Epo), which is known to activate the signal transducer and activator of transcription, STAT-5. To determine if Kit signal transduction activated latent DNA-binding factors, including STAT-5, we performed electrophoretic mobility shift assays on stem cell factor (SCF)-stimulated mouse bone marrow-derived mast cells (BMMCs). SCF led to the rapid and transient activation of a DNA-binding factor that was identified by supershift analysis as STAT-5. STAT-5 DNA binding was shown to be specific for the oligonucleotide of the correct sequence and was dose-responsive. Epo stimulation of BMMCs led to the activation of a DNA-binding activity that comigrated with the SCF-induced band, but peaked and was maintained at later time points than SCF-induced activation. These data indicate that SCF stimulation of Kit leads to activation of STAT-5 DNA binding with kinetics distinct from Epo-mediated stimulation.

Animals↗

Utility of the Barona demographic equations to estimate premorbid intelligence: information from the WAIS-R standardization sample.

The WAIS-R (Wechsler, 1981) and elderly WAIS-R standardization samples (Ryan, Paolo, & Brungardt, 1990) were combined to evaluate the utility of the Barona demographic regression equations (Barona, Reynolds, & Chastain, 1984) to estimate premorbid intelligence. The equations underestimated ability for persons with IQs less than 80 and overestimated ability of subjects with IQs greater than 119. The equations also overestimated the IQs of 247 persons with confirmed brain dysfunction. Because this overestimation occurred for impaired persons with IQs less than 90, it is difficult to determine whether the difference reflects true intellectual deterioration or statistical artifact. Abnormal cut-off scores at the 10% and 5% levels are provided to allow clinicians to detect abnormal discrepancies between the estimated and obtained IQs.

Adolescent↗

Decrease in milk and blood dioxin levels over two years in a mother nursing twins: estimates of decreased maternal and increased infant dioxin body burden from nursing.

This study addresses the issue of breast-feeding and its reduction of maternal dioxin body burden. Nursing is also a source of infant dioxin exposure. This study extends our previous efforts to investigate a nursing mother's milk and blood dioxin levels. We report polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) dioxin toxic equivalents (TEQs) in milk (M) and blood (B) both before and also after two years of nursing twins to be 16.9 ppt (M), 14.9 ppt (B), and 3.1 ppt (M) and 4.9 ppt (B), respectively. The ratios of measured congeners comparing milk to whole blood from a nursing mother taken initially and after two years of nursing vary from 0.36 to 8.40 in 1992 and 0.17 to 1.0 in 1994. The mother's body burden was initially calculated to be 329 ng TEQ from milk levels and 291 ng TEQ from blood levels using samples taken in February 1992 and decreased to 60.1 ng TEQ from milk and 96 ng TEQ from measured blood using samples collected in December 1994. We calculate that the excretion of dioxin TEQ by the mother through breast-feeding is 269 ng TEQ, which is similar to the 303 ng TEQ estimated total dioxin intake by the twins over two years. The average daily dioxin intake from nursing is 66 pg TEQ/kg-BW/day for each twin over the two years.

Benzofurans↗

Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3-dependent and independent pathways.

Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3. Although JAK3 is required for proper lymphoid development, the precise roles of this kinase in IL-2 and IL-4 signaling in lymphocytes have not been defined. Here, we have studied IL-2 and IL-4 signaling in B cell lines lacking JAK3. Although IL-2-induced phosphorylation of IL-2R beta, JAK1, and STAT5 all required the presence of JAK3, IL-4-mediated phosphorylation of JAK1, STAT6, and insulin receptor substrates 1 and 2 did not. However, IL-4-induced effects were clearly improved following JAK3 expression. These data indicate that IL-4 signaling occurs in the absence of of JAK3, but is comparatively inefficient. These findings may help in understanding the pathogenesis of the immunodeficiency that occurs with mutations of JAK3 and may suggest a mechanism for the pleiotropic effects of IL-4.

B-Lymphocytes↗

Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.

IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.

Amino Acid Sequence↗

Stability of WAIS-R scatter indices in the elderly.

The test-retest reliability and clinical stability of WAIS-R VIQ-PIQ differences, inter, and intrasubtest scatter were investigated in a sample of 61 normal persons 75 years and older. The test-retest coefficient was.76 for VIQ-PIQ discrepancy, ranged from.05 to.56 for the intersubtest scatter range, and from.08 to.43 for intrasubtest scatter. In terms of clinical stability, 56% of subjects maintained a similar magnitude and direction of meaningful VIQ-PIQ differences from test to retest. Classification of subtest strengths and weakness from test to retest was generally poor with an average disagreement of 52% from the first to the second assessment. Intrasubtest scatter also displayed poor clinical stability with 25-50% of subjects demonstrating meaningful changes on retest.

Journal Article↗

WAIS-R verbal-performance IQ discrepancies in persons with lateralized lesions: utility of a seven subtest short form.

WAIS-R Verbal-Performance IQ difference scores for Ward's (1990) seven subtest short form and the complete WAIS-R were examined in patients with lateralized and diffuse lesions. For both versions, the expected Performance > Verbal pattern was observed in the right hemisphere lesion group, while no summary score differences were seen in the left hemisphere group. Verbal-Performance IQ discrepancies for the short form fell within +/- 5 points of the WAIS-R discrepancy scores in about 75%of the cases, regardless of lesion location. Statistically reliable IQ differences between the complete and abbreviated WAIS-R attained 66%, 91%, and 89% agreement for the left, right, and diffuse groups, respectively. The results support the clinical utility of the seven subtest short form.

Journal Article↗

Mast cells lacking the high affinity immunoglobulin E receptor are deficient in Fc epsilon RI gamma messenger RNA.

A population of cells that express mast cell markers, including the membrane protein p161, but that lack expression of the high affinity IgE receptor, Fc epsilon RI, can be routinely grown from bone marrow. Ionomycin, but not IgE immune complexes, causes these cells to release serotonin and to express IL-3 and IL-13 mRNA, consistent with their being FC epsilon RI-deficient mast cells. These p161+/Fc epsilon RI- mast cells expressed normal amounts of Fc epsilon RI alpha and beta chain mRNA, but extremely low levels of Fc epsilon RI gamma chain mRNA. In addition, this novel mast cell population expressed CD3 zeta chain mRNA, which p161+/Fc epsilon RI+ mast cells did not. CD3 zeta stable transfectants of Abelson-murine leukemia virus-transformed p161+/Fc epsilon RI+ mast cells continued to express Fc epsilon RI. This strongly suggests that the failure of p161+/Fc epsilon RI- mast cells to express IgE receptors was not caused by the presence of CD3 zeta chain. Transfection of human Fc epsilon RI gamma cDNA into p161+/Fc epsilon RI- mast cells rescued IgE binding. These stable transfectants released serotonin in response to cross-linkage of Fc epsilon RI, demonstrating that the molecular defect of p161+/Fc epsilon RI- mast cells is indeed the loss of Fc epsilon RI gamma expression.

Animals↗

Bcl-2 protects murine erythroleukemia cells from p53-dependent and -independent radiation-induced cell death.

To better understand the molecular basis of radiation-induced cell death, we studied the role of the bcl-2 oncogene and the p53 tumor suppressor gene in this process. A temperature-sensitive mutant of murine p53 (p53Val-135) and/or bcl-2 was transfected into murine erythroleukemia cells (MEL, DP16-1, which are null in p53). We demonstrate that radiation-induced cell death occurs by both p53-dependent and -independent pathways and overexpression of bcl-2 modulates both pathways. When viability was measured 24 h post-radiation, cells that had been briefly exposed to wtp53 immediately after X-ray irradiation had decreased survival as compared to unirradiated cells expressing wtp53 or X-ray irradiated DP16-1 cells. However, at later times X-ray irradiated parental DP16-1 cells also had decreased survival compared to the unirradiated control. This decrease in survival began 48 h following radiation. Bcl-2 prevented radiation-induced cell death in DP16-1 cells expressing wtp53 and delayed radiation-induced cell death in DP16-1 cells without wtp53. X-ray irradiated cells expressing wtp53 displayed microscopic and biochemical characteristics consistent with cell death due to apoptosis. DP16-1 cells which were untransfected or co-transfected with wtp53 and bcl-2 displayed characteristics of cells undergoing necrosis. These results suggest that radiation-induced cell death occurs by both p53-dependent and p53-independent pathways. The p53-dependent pathway results in cell death via apoptosis and occurs approximately 24 h following radiation. The p53-independent pathway does not appear to involve apoptosis and occurs at a later time, starting 48 h after X-ray exposure. Thus, bcl-2 protects cells from p53-dependent radiation-induced apoptotic cell death and attenuates p53-independent radiation-induced cell death.

Animals↗

Comorbidity of dissociative disorders among patients with substance use disorders.

OBJECTIVES: The study replicated methods used in an earlier study to determine the prevalence of dissociative disorders among patients with substance use disorders and to examine demographic characteristics and history of childhood abuse among patients with and without dissociative comorbidity. METHODS: A total of 100 inpatients who were completing a substance abuse treatment program at a VA medical center were interviewed using the Dissociative Disorders Interview Schedule, which diagnoses dissociative disorders. Two additional screening measures of dissociative symptoms were used, as well as an instrument to measure IQ. RESULTS: Fifteen percent of the sample were diagnosed as having a dissociative disorder. Compared with patients without a dissociative disorder, the patients with a dissociative disorder had significantly higher median scores on the two screening measures, indicating more dissociative experiences and the presence of five distinct symptom clusters. The two groups did not differ in history of childhood abuse or IQ. CONCLUSIONS: The results support earlier findings suggesting that patients with substance abuse disorder should be routinely screened for dissociative symptoms and disorders.

Adult↗

Cognitive estimation in traumatic brain injury: relationships with measures of intelligence, memory, and affect.

Brain injury is associated with a reduced capcity to engage in effective cognitive estimation. The current study utilized two measures of this construct, the Cognitive Estimation Test (CET) and Luria Memory Test (Luria), to investigate the relationships between cognitive estimation and intelligence, memory, and affect in a sample of 30 traumatically brain-injured individuals. Results demonstrated significant correlations between cognitive estimation and tests of intelligence and memory. However, measures of depression and state anxiety were not meaningfully associated with cognitive estimation. The ability to recall stories accounted for the greatest portion of the variance for both the CET and Luria. Specifically, the 30-minute Logical Memory subtest from the Wechsler Memory Scale-Revised accounted for 38% of the variance in the CET, while the Logical Memory 30-minute savings score accounted for 47% of the variance in the Luria. Intellectual and affective variables explained only negligible amounts of variance on cognitive estimation tasks.

Adult↗

Testosterone-secreting adrenal adenoma that contained crystalloids of Reinke in an adult female patient.

We describe a testosterone-secreting adrenal adenoma that contained crystalloids characteristic of Leydig cells in a 55-year-old woman with virilization, in whom results of a steroid biochemical profile were normal except for a substantially increased serum testosterone level. After right adrenalectomy, the serum testosterone level returned to normal and has remained within the normal range 2 years postoperatively. Histologic examination confirmed the diagnosis of a testosterone-secreting adrenal adenoma with crystalloids of Reinke specific for Leydig cells. The exact pathogenesis of these testosterone-secreting adrenal adenomas is still unclear. Although crystalloids of Reinke have been identified in only three cases, their absence does not exclude a Leydig cell character in the rest of the reported cases. Our case provides additional support for the hypothesis that Leydig cells are present in the adrenal gland and may have an active role in the pathogenesis of testosterone-secreting adrenal tumors; thus, such cells should be sought in every case.

Adenoma↗

Pheochromocytoma associated with polycythemia: case report.

Secondary polycythemia has been noted in association with various neoplasms. An erythropoiesis stimulating factor (erythropoietin) has been demonstrated in the fluid or tissues obtained from most of these neoplasms and erythropoietin levels were found to be elevated in the serum and returned to normal after resection of these tumors. Recently, the potential of pheochromocytoma to produce a wide variety of hormones and neurotransmitters such as growth hormone, motilin, ACTH, atrial natriuretic factor (ANF) and others has been shown. Although elevated hematocrit has been observed in association with pheochromocytomas, the occurrence of absolute polycythemia in such cases is very rare. In this report, we describe a patient with a long history of hypertension and cardiac dysrhythmia as well as polycythemia which was secondary to pheochromocytoma. The patient's blood pressure normalized and the polycythemia regressed after resection of the tumor. Increased release of erythropoietin is the most favored explanation for this rare association. Pheochromocytoma should be included in the differential diagnosis of secondary polycythemia.

Adrenal Gland Neoplasms↗

[Change of PCDF and PCB concentrations in the blood of Yucheng and Yusho patients for 25 years].

The blood samples of 3 Yucheng patients collected 6-7 times from 1980 to 1993 and 5 Yusho patients collected 6-8 times from 1982 to 1993 were analyzed for congeners of polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) by high resolution gas chromatography-mass spectrometry and gas chromatography-electron capture detection. In the blood of Yucheng patients, the high concentrations of 3 PCDF congeners, 2,3',4, 4',5-penta-CB and 5 PCB congeners were eliminated at half-lives of 2.4-2.9, 1.7 and 4.1-6.1 years, respectively, while in Yusho patients, 14 years after the incident, their half-lives were converted to longer times as observed 3.2-13.4, 24.0 and 13.7-34.2 years, respectively. In the same Yucheng and Yusho patients, the half-lives of the 5 PCB congeners were about twice longer than those of the 3 PCDF congeners. PCBs are more retainable than PCDFs in human blood.

Adult↗

c-myc and bcl-2 modulate p53 function by altering p53 subcellular trafficking during the cell cycle.

We have studied the ability of c-myc and bcl-2 oncogenes to modulate p53 function. Our studies show that coincident expression of human Bcl-2 protein with p53 prolongs survival of murine erythroleukemia cells. This effect was associated with a loss of the G1 specificity of p53-mediated cell cycle arrest. Furthermore, we found that the c-myc and bcl-2 genes cooperate to inhibit p53 functions. Coexpression of bcl-2 and c-myc can totally overcome p53-induced apoptosis and cell cycle arrest by altering the subcellular trafficking of p53 during the cell cycle: the p53 remains in the cytoplasm of the cotransfected cells during a critical period in G1. This finding suggests a mechanism by which normal hematopoietic progenitors can survive and proliferate despite p53 expression and by which the inappropriate expression of bcl-2 and c-myc can cooperate in transformation.

Animals↗

Role for the stem cell factor/KIT complex in Schwann cell neoplasia and mast cell proliferation associated with neurofibromatosis.

Schwann cells are the primary cell type in the disfiguring lesions associated with neurofibromatosis type 1 (NF-1). These lesions also contain abnormally high numbers of mast cells, a cell type which develops in response to stem cell factor. We report here that neonatal and adult rat and human Schwann cells, as well as a transfected rat Schwann cell line and a human Schwannoma line derived from an NF-1 patient, all produced stem cell factor mRNA and protein. In coculture experiments, surface expression of stem cell factor by neonatal rat Schwann cells was profoundly downregulated by contact with dorsal root ganglion neurites. The receptor for stem cell factor, KIT, was not expressed in normal Schwann cells but was expressed in the human Schwannoma line, suggesting that aberrant KIT expression may form an autocrine loop in certain Schwann cell neoplasias.

Animals↗