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Biomedical subjects

C Ryan

Publications and source records attributed to C Ryan.

At least 19 recordsLinked to original sources
PubMed1997

Graft versus host disease in rats made tolerant for organ allografts.

Tolerance for organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. A potential hazard of tolerance is the susceptibility to graft vs host disease (GVHD) due to unresponsiveness to alloantigen. This study sought to determine if our model of tolerance induction results in susceptibility to GVHD. Chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post-BMTx by flow cytometric analysis of recipient spleens for the presence of ACI cells. ACI/Lew chimeras (ALC), animals that reconstituted only with syngeneic (Lewis) marrow (so-called failed chimeras), and ACI/Lew F1 (LACF1) hybrid rats were all given 200 x 10(6) ACI splenocytes i.v. Animals were examined for evidence of GVHD. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 (n = 6) rats developed severe lethal GVHD following ACI splenocyte injection. Similarly, ALC (n = 6) developed fatal GVHD. Animals that reconstituted only with syngeneic Lewis marrow (failed chimeras) showed no signs of illness. GVHD was confirmed histologically and immunohistochemically. Failed chimeras receiving ACI splenocyte challenge showed no evidence of GVHD histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras and hybrids but not in the failed chimeras. We conclude that tolerance induction by mixed chimerism results in susceptibility to GVHD if enough donor lymphoid tissue is given to the host at the time of organ transplant. Animals that are not mixed chimeras (failed bone marrow transplant) rejected the allogeneic splenocytes as evidenced by their lack of disease. Tolerance may therefore make the host defenseless against fatal GVHD.

Animals↗
PubMed1997

Mild pyelectasis ascertained with prenatal ultrasonography is pediatrically significant.

Isolated 'mild renal collecting system dilatation' (mild pyelectasis) is a common prenatal sonographic finding. An association between mild pyelectasis and fetal aneuploidy has been established, but in the absence of a concomitant anomaly, mild pyelectasis is usually regarded as benign and of no clinical consequence, and follow-up is often not obtained after the initial ascertainment. To test this, we investigated the relationship between mild pyelectasis and (1) progression to hydronephrosis; (2) postnatal vesicoureteral reflux (VUR); and (3) postnatal surgery. Between 1 January 1992 and 1 January 1995, we performed 453 prenatal sonographic examinations of 306 patients with mild fetal pyelectasis and no other anomalies. During the course of a routine sonographic examination, we performed a detailed evaluation of the fetal genitourinary tract, Mild pyelectasis was defined as a pelvocalyceal fluid-filled space with the smallest of two transverse perpendicular sonographic measurements of > or = 4 mm and < 10 mm. Hydronephrosis was defined similarly, but with a measurement of > or = 10 mm. Postnatal urological assessment was obtained with routine renal ultrasonography, and voiding cystourethrography (VCUG), measurement of 99mTc-labelled diethylenetriamine pentaacetic acid (DPTA) mercaptacetyltriglycerine (MAG3), and intravenous pyelogram, as necessary. After exclusion criteria were applied, 294 (96%) patients with isolated fetal pyelectasis were considered. A total of 251 (82%) of these were followed with ultrasonography prenatally and during the postnatal period. Two or more prenatal examinations were carried out in 129 patients (51%) and in 35 (27%) of these cases the biometry progressed to frank hydronephrosis (> 10 mm). In only six (5%) of the cases followed prenatally did the measurement diminish to < 4 mm. We found a greater variability in prenatal renal biometry throughout gestation in infants found to have VUR, when compared with those who had no VUR. On postnatal follow-up, 84 patients had VCUG. Sixteen of these patients (6% of all patients [16/251] and 19% [16/84] of those who had the test) were found to have an abnormal finding. Whereas the prenatal appearance of mild pyelectasis improved in only a small number of cases, we found that it progressed to hydronephrosis in 27% of cases. Postnatal evaluation found VUR to be common in apparent uncomplicated mild prenatal pyelectasis. Although postnatal surgery was necessary in only a small number of cases, surgical intervention was necessary in 33% (four of 12) of those with VUR.

Adolescent↗
PubMed1997

Metabolite changes associated with heat shocked avian fibroblast mitochondria.

A previous report from our laboratory (Collier et al 1993) showed that the elongated tubules of mitochondria in the cytoplasm of cultured chicken embryo fibroblasts collapsed to irregularly shaped structures surrounding the nuclear membrane after a 1 h heat shock treatment. The normal mitochondrial morphology reappeared upon removal of the thermal stress. We have now determined that several changes occurred in mitochondrial-related metabolites under these same heat shock and recovery conditions. Among these were significant decreases in the levels of fumarate and malate and increases in the amounts of aspartate and glutamate. In contrast, other intermediates of the tri-carboxylic acid cycle were unaltered as were levels of ATP and phosphocreatine. The changes observed might result from heat shock-induced changes in enzyme activities of the mitochondria, from alterations in the membrane-embedded specialized carrier proteins that transport metabolites between cytosol and mitochondria or from a disorganization of the electron-transport system normally coupled to oxidative metabolism. The rapid recovery, however, suggested that these changes were transient and readily reversible.

Adenosine Triphosphate↗
PubMed1996

Disruption of the erp/mkp-1 gene does not affect mouse development: normal MAP kinase activity in ERP/MKP-1-deficient fibroblasts.

Externally regulated phosphatase (ERP or MKP-1) is a dual specificity phosphatase that has been implicated in the dephosphorylation of mitogen activated protein kinases (MAP kinases). MAP kinase is activated in response to external signals and in turn phosphorylates proteins essential to the regulation of cell growth. To study the role of ERP/MKP-1 protein in mammalian development and its function in signal transduction we have generated mice, embryonic stem (ES), cells and mouse embryo fibroblasts (MEFs) that are deficient in the ERP/MKP-1 protein. ERP/MKP-1-deficient mice are born at normal frequency, are fertile and present no phenotypic or histologic abnormalities. MAP kinase activity and the induction of c-fos mRNA is unaltered in MEFs lacking the ERP/MKP-1 protein, indicating no alteration of the MAP kinase pathway. In addition, ERP/MKP-1 deficient MEFs grow and enter DNA synthesis at the same rate as control cells. Our results demonstrate that the activity of ERP/MKP-1 is not essential for embryo development and indicate that the lack of ERP/MKP-1 activity can be compensated by other phosphatases in vivo.

Animals↗
PubMed1996

Testing the global-slowing hypothesis: are alcohol's effects on human performance process-specific or task-general?

In an interesting recent meta-analysis, Maylor and Rabbitt (1993) suggested that alcohol's effects on human performance may not be process- or stage-specific, but reflect a general, undifferentiated, cognitive slowing. According to this view, performance is globally slowed by a constant multiplicative fraction (b), such that the longer a process takes without alcohol on board (a -), the more it will be slowed by alcohol (a +). In summary: RTa+ = b b (RTa-). In this sense, the effects of alcohol are determined simply by the duration of a process or stage--not by its function or content--and attempts to map the effects of alcohol to specific cognitive operations are essentially futile. This global-slowing hypothesis entails, then, (i) that the function relating RTa+ to RTa- will be linear and increasing; (ii) that the value of b will be significantly greater than 1.0; and (iii) that all experimental factors which increase the complexity (hence, duration) of a task or stage will interact with alcohol. In this study we tested the global-slowing hypothesis directly using fixed set, varied set and concurrent sets item-recognition paradigms. All three tasks showed convincing additivity between alcohol and other key experimental factors which affect response latency (e.g., setsize, response type); there was no hint of any of the spectrum of significant interactions predicted by the global-slowing hypothesis. A meta-analysis of varied set latencies, analogous to Maylor and Rabbitt's, yielded a reasonably linear alcohol/no-alcohol function, but with a slope constant (b) less than 1.0. In all, the data provided little support for the global-slowing hypothesis.

Adolescent↗
PubMed1996

Gender, type of treatment, dysfunctional attitudes, social support, life events, and depressive symptoms over naturalistic follow-up.

OBJECTIVE: The present study investigated gender differences in depressive symptoms during a naturalistic follow-up for outpatients with major depressive disorder in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Specifically, the study investigated whether gender interacted with type of treatment received, dysfunctional attitudes, life events, or social support to predict severity of depressive symptoms. In addition, aspects of these psychosocial factors (need for approval, interpersonal life events, and close friendships), hypothesized to be more salient for women, were examined to determine if they had a differential impact on level of depressive symptoms in men and women. METHOD: Assessments conducted 6, 12, and 18 months after treatment included measures of depressive symptoms, dysfunctional attitudes, current life events, and social support. Data were available for 188 subjects (134 women and 54 men). Regression analyses were conducted to examine whether gender as a main effect, or interacting with dysfunctional attitudes, life events, social support, or subtypes of these variables, predicted cross-sectional or longitudinal measures of depressive symptoms during follow-up. RESULTS: A consistent finding of the study was that over the 18 months of this naturalistic follow-up, there were no main effects for gender or any significant interactions involving gender and any of the variables of interest. The study demonstrated that life events and social support were related to severity of depressive symptoms for both genders. CONCLUSIONS: Despite differential prevalence rates of major depression for men and women, findings do not support a different process in outcome of illness for men and women.

Adult↗
PubMed1995

Day case oral surgery: a review of 25 years experience at the Dublin Dental Hospital.

A retrospective analysis of the changing work-load at the Dublin Dental Hospital oral surgery day case unit was undertaken. This involved 26,697 operations performed during the 25-year period 1968-1992. The results show how the practice of oral surgery has changed over this time. Annual totals ranged from 766 to 1549 operations. While most categories of operations remained largely unchanged, the removal of impacted third molars increased from 10.5% of the annual total to 57.0%. Routine extractions of permanent teeth decreased from 53.9% of the annual total to 18.0%.

Ambulatory Surgical Procedures↗
PubMed1995

28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells.

Because of their differentiating effects in neoplastic cells in vitro, the use of retinoids in the treatment of various malignant and premalignant conditions is under investigation. To date, signal transduction pathways involved in retinoid-induced differentiation remain poorly understood. Differentiation of HL-60 cells by all-trans-retinoic acid (tRA) is directly mediated by down-regulation of the serine protease myeloblastin (mbn). In this report, we investigate the possibility that the 28-kDa heat shock protein (hsp28), previously linked to differentiation of normal and neoplastic cells including HL-60, may be regulated by mbn. Using NB4 promyelocytic leukemic cells as a differentiative model, we show that tRA induces initial suppression and subsequent up-regulation of hsp28 protein, mirroring tRA-induced changes in mbn protein. The progressive reduction in hsp28 mRNA levels in response to tRA suggests that changes in hsp28 protein levels might be posttranscriptionally mediated, raising the possibility that hsp28 may be targeted by mbn. To address this, we developed an assay using purified mbn and recombinant hsp28 and now show that hsp28 is hydrolyzed by mbn but not its homologue, human neutrophil elastase. Moreover, mbn does not indiscriminately hydrolyze other proteins. Identifying hsp28 as a substrate of mbn strongly suggests that hsp28 may be a key component of the tRA signaling pathway involved in regulating cell differentiation.

Cell Differentiation↗
PubMed1995

The effects of repeated treatment with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the lever press responding of the rat under FI and DRL schedules of food reinforcement.

In general, the effects of 8-OH-DPAT on the body temperature of rats or in inducing the 5-HT syndrome show rapid tolerance. However, in contrast, the 8-OH-DPAT-induced increase in the activity of rats in a two-way active avoidance task only occurs after repeated administration, i.e. there is sensitisation. The present study was conducted to examine whether this developing hyperactivity may also be expressed as increased rates of lever press responding, and if so, under which conditions it occurs. Rats were trained to press levers under fixed interval 60-s (FI 60) or differential reinforcement of low rates 20-s or 72-s (DRL20, DRL72) schedules of food reinforcement. Groups of trained rats were then treated daily 5 min before testing with doses of 0.01, 0.1 and 1.0 mg/kg 8-OH-DPAT SC for 10-21 days. In all three procedures, in the first couple of days of drug treatment, 8-OH-DPAT generally suppressed lever pressing in a dose-dependent manner. Thereafter, tolerance to this effect was seen to a greater (DRL20, DRL72) or lesser (FI60) extent. Some evidence for stimulation of low rates of lever press responding was seen after 10 days treatment under FI60, but not in DRL20 or DRL72 during short 30 to 60 min long daytime tests although in the latter case, the rats responded to the stimulating effects of 0.8 mg/kg SC amphetamine administered once at the end of the experiment. However, when rats were allowed to respond under DRL72 testing for 12 h during the night, after 10 days treatment a clear stimulation of lever pressing was observed. This stimulation was not specific to lever pressing, however, since a stimulation of entries into the food tray and licking were also seen. From these results, it may be concluded that the stimulating effect of 8-OH-DPAT after repeated administration may be expressed as increased rates of lever pressing, but not under all conditions in which psychomotor stimulation by amphetamine is seen. The potential for 8-OH-DPAT and related compounds to stimulate motor responding in this way should be taken into account when interpreting the effects of these drugs in animal models of psychiatric disorders.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Effects of acute hyperglycemia on mental efficiency and counterregulatory hormones in adolescents with insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether acute hyperglycemia adversely affects mental efficiency to the same extent as acute mild hypoglycemia. STUDY DESIGN: We administered a battery of cognitive tests to adolescents studied at hyperglycemic (20 mmol/L (360 mg/dl)), hypoglycemic (3.3 mmol/L (60 mg/dl)), or euglycemic (5.5 mmol/L (100 mg/dl)) targets, which were maintained by an insulin-glucose clamp. The study included 36 children, 9 to 19 years of age (mean = 14.7 years), with diabetes duration more than 2 years (mean = 6.9 years). RESULTS: Cognitive test performance did not deteriorate during hyperglycemia. In contrast, there was a significant decline in performance on all cognitive tests during mild hypoglycemia. Autonomic symptoms did not change significantly during hyperglycemia or during the rapid return from hyperglycemia to euglycemia. Although significant increments in epinephrine and pancreatic polypeptide levels occurred during mild hypoglycemia, no changes in counterregulatory hormones occurred during hyperglycemia. An exploratory regression analysis demonstrated that changes in mental efficiency were best predicted by increases in pancreatic polypeptide, a marker of autonomic activation. CONCLUSION: These results confirm our previous finding that mild hypoglycemia causes transient decrements in cognitive function. In contrast, neither hyperglycemia, nor the rapid drop from acute hyperglycemia to euglycemia, affected symptoms, cognitive function, or counterregulatory hormone secretion.

Acute Disease↗
PubMed1995

Unintentional weight loss in long-term care: predictor of mortality in the elderly.

We retrospectively reviewed the medical records of 153 long-term care residents. Of these, 24 had lost at least 5% of their body weight during a 1-month interval. An unmatched control group of 51 patients was randomly selected from the remaining patients. Subjects who lost at least 5% body weight in 1 month were 4.6 times more likely to die within 1 year. Using multiple logistic regression, the odds ratio for weight loss and mortality was 5.1 (95% confidence interval 1.5 to 17.1) after adjustment for potential confounding by age and sex. The relatively simple anthropometric measure of body weight could be used by a multidisciplinary team in long-term care settings to identify patients at increased risk of dying. Further work is needed to clarify the role that nutrition could play in decreasing mortality in long-term care facilities.

Aged↗
PubMed1995

Rapid assay for mycobacterial growth and antibiotic susceptibility using gel microdrop encapsulation.

Effective control of tuberculosis transmission in vulnerable population groups is dependent on rapid identification of the infectious agent and its drug susceptibility. However, the slow growth rate of mycobacteria has undermined the ability to quickly identify antimicrobial resistance. These studies describe a mycobacterial growth assay based on microencapsulation technology used in conjunction with flow cytometric analysis. Mycobacteria were encapsulated in agarose gel microdrops approximately 25 microns in diameter, and colony growth was monitored by using flow cytometry to evaluate the intensity of auramine staining after culture for various times at 37 degrees C. By this method, colony growth of Mycobacterium bovis and M. smegmatis could be quantified within 1 to 3 days after encapsulation. Inhibition of growth by rifampin and isoniazid was also evaluated in this time period, and the presence of an isoniazid-resistant subpopulation representing 3% of the total microorganisms could be detected. This use of encapsulation and flow cytometry has the potential to facilitate rapid and automated evaluation of inhibition of growth by antimicrobial agents and shorten the time frame for analysis of clinical specimens.

Bacteriological Techniques↗
PubMed1995

Distinguishable substrate pools for muscle glyconeogenesis in lactate-supplemented recovery from exercise.

The formation of muscle glycogen from substrates other than glucose (glyconeogenesis) has now been demonstrated 1) from circulating lactate when this lactate is elevated and 2) from intramuscular substrate, which equilibrates with the products of local glucose metabolism but not with circulating lactate [Am. J. Physiol. 267 (Endocrinol. Metab. 30): E210-E218, 1994]. The purpose of the present studies was to examine the interaction of recovery from low-intensity exercise (4-h swim) and supplementation with exogenous lactate in determining the distribution of carbon flux between these two pathways for the glyconeogenic process in the gastrocnemius muscles. Ten protocols were defined using [14C]bicarbonate (no local incorporation into glycogen), [U-14C]lactate (tracks circulating lactate), and recycled [1-14C]glucose (tracks local substrate formation and glyconeogenesis). During recovery, lactate was infused to increase circulating concentrations 15- to 20-fold. Glucose and saline infusions during recovery were used as controls. The results indicate that prior exercise primarily promotes the local incorporation of recycled glucose label produced within the muscle into glycogen. Exogenous lactate stimulates the incorporation of circulating lactate into muscle glycogen. The contribution of the two substrate pools to glycogen synthesis appears to be additive, indicating the independence of muscle glycogenesis from these two sources.

Animals↗