Recognition of Rat Dendritic Cells by a Monoclonal Antibody

A mouse monoclonal IgM antibody reactive with dendritic cells (DC) from the Brown Norway (BN) rat was prepared. This antibody (1F119) binds to a membrane-bound antigen present on DC from thoracic duct lymph, spleen, thymus, and lymph node. The antigen is present only in low density on 5% of splenic macrophages (M phi) and absent from peritoneal M luminal diameter. In situ, the antibody exhibits a strong reactivity towards DC in the thymic medulla, whereas no reaction is observed with cortical cells. Furthermore, cells positive for 1F119 can be identified in T-cell areas of spleen, lymph node, and Peyers' patches. 1F119 was genetically restricted in that a strong reactivity was found with DC from rats of the RT1n and RT1u haplotypes, an intermediate reactivity with the RT1c haplotype, only a weak reactivity with the RT1l and RT1b haplotypes, and no reactivity with the RT1a and RT1k haplotypes. The relatively weak reactivity of 1F119 with respect to the RT1l haplotype also appeared from a weak binding of 1F119 to DC from Lewis rats, as was assessed by FACS analysis. This result was comparable to the binding of OX3 (RT1.Bl and RT1.Bu) to DC from BN rats. Studies performed on thymus sections of recombinant rat strains indicate that 1F119, despite its apparent specificity for DC, reacts with a polymorphic RT1.B product.     

Ten-year stability of cardiovascular responses to laboratory stressors

In this study we examined test-retest stability of cardiovascular stress responses over a decade of the life span. Participants were 55 male college undergraduates. 19 years of age at initial testing, and 29 years of age at follow-up testing Stressors were a foot cold pressor and an aversive reaction time task. Cardiovascular measures included systolic and diastolic blood pressure, heart rate, and preejection period. For cold pressor, the magnitude and pattern of cardiovascular responses remained unchanged at the 10-year follow-up. For the reaction time task, the characteristic cardiovascular response patterns was preserved but with significant attenuation of magnitude. The present findings are consistent with previous observations of temporal stability but over a substantially longer test-retest interval. The long-term stability of stress responses is discussed in the context of stress test methodology, behavioral response demands, and maturation of the physiological systems involved in cardiovascular response expression.     

Spontaneous Neoplasms in Control Wistar Rats

Neoplastic data on 1370 control Wistar rats from 10 carcinogenicitybioassays done between 1980 and 1990 were reviewed. Mean percentagesurvival at 104 weeks was 58% for males and 59% for females.A total of 1857 neoplasms were diagnosed in 466 (68%) male and582 (85%) female rats; 1390 were benign and 467 were malignant(12% with metastasis). Seventy-four percent of all neoplasmswere in endocrine and reproductive systems. Most common neoplasms(affecting more than 7% of either sex) were pituitary adenoma(27.7% males; 55.0% females), mammary fibroadenoma (1.0% males;25.3% females), mammary adenocarcinoma (1.0% males; 13.1% females),adrenal cortical adenoma (8.3% males; 9.3% females), and endometrial stromal polyp (9.6% females). Fourteen neoplasms affecting2 to 6% of either sex included adrenal pheochromocytoma, thyroidC cell adenoma, thyroid follicular adenoma, pancreatic isletcell adenoma, lymphoma, histiocytic sarcoma, thymoma, hepaticadenoma, pancreatic acinar adenoma, mammary adenoma, dermalfibroma, astrocytoma, testicular interstitial cell tumor, andovarian granulosa cell tumor. Remaining neoplasms were seenin less than 2% of animals.     

ATP1A3 mutations in infants: a new rapid‐onset dystonia–Parkinsonism phenotype characterized by motor delay and ataxia

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the ATP1A3 gene. In adults, mutations in ATP1A3 cause rapid‐onset dystonia–Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and samples were collected for mutation analysis. Case 1 presented with fluctuating spells of hypotonia, dysphagia, mutism, dystonia, and ataxia at 9 months. After three episodes of hypotonia, she developed ataxia, inability to speak or swallow, and eventual seizures. Case 2 presented with hypotonia at 14 months and pre‐existing motor delay. At age 4 years, he had episodic slurred speech, followed by ataxia, drooling, and dysarthria. He remains mute. Both children had ATP1A3 gene mutations. To our knowledge, these are the earliest presentations of RDP, both with fluctuating features. Both children were initially misdiagnosed. RDP should be considered in children with discoordinated gait, and speech and swallowing difficulties.     

Effects of Changes in the L‐Type Calcium Current on Hysteresis in Restitution of Action Potential Duration

Background : Electrical restitution and memory of action potential duration (APD) are considered key determinants of stability of activation. Calcium handling also impacts stability of activation via its modification of the above and independently. We determined the effects of reduction in an important calcium current, I_CaL, on hysteresis in restitution of APD, which provides assessment of restitution and memory. Methods : Transmembrane potentials were recorded from isolated ventricular tissues from pigs. The pacing protocols consisted of sequential and oscillatory changes in diastolic intervals (DI). Two protocols were used, one where DIs ranged between 100 and 700 ms and the other where DIs ranged between 10 and 290 ms. Verapamil (2 μM/L) was used to reduce I_CaL. From the hysteresis observed in restitution, loop area, thickness, overall tilt, and the maximum and minimum delays between DIs and APDs were calculated to obtain measures of memory and restitution. Results : Restitution during sequential and oscillatory changes in DI displayed hysteresis. All measures of hysteresis decreased after reduction in I_CaL. The decreases in area, thickness, and overall tilt were most pronounced (50%, 50%, and 33%). Conclusion : Sequential and oscillatory changes in DIs reveal that while the overall slope of restitution of APD decreases with decrease in I_CaL, so do measures of memory. Because slopes and memory are considered to have contrasting effects on stability, our results suggest that predicting effects of alteration in I_CaL on stability of activation using slope alone may not be adequate. (PACE 2010; 451–459)     

The histories of withdrawal convulsions and delirium tremens in 1648 alcohol dependent subjects

A small proportion of alcohol-dependent men and women experience delirium tremens (DTs) and/or convulsions during alcohol withdrawal. While some characteristics of individuals most likely to show these severe sequelae of the abstinence syndrome have been described, it is not clear whether these risk factors operate independently in their association with severe withdrawal. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview was used to evaluate 1648 alcohol dependent men and women (including 540 women). The background characteristics and drinking histories of the 160 men and 51 women (12.8% of the subjects) who reported ever having had at least one episode of DTs and/or convulsions during withdrawal were compared with the characteristics of the remaining alcohol dependent individuals. Compared to other alcohol-dependent subjects, those with histories of severe withdrawal reported a greater maximum number of drinks in any 24–hour period (40.9±25.71 versus 24.9 ±17.72), more withdrawal episodes (28.2 ±33.74 versus 15.9 ±26.84), more non-medicinal use of sedative-hypnotics (56.4% versus 32.9%) and a greater number of medical problems. Hierarchical logistic regression analysis revealed that the most powerful differences between those with histories of more and less severe withdrawals related to the maximum number of drinks per day and the total number of withdrawal episodes. The remaining variables still added significantly to the relationship to more severe withdrawal. The etiology of DTs and convulsions is complex and involves the interaction of diverse characteristics representing relatively unique domains. It is hoped that these data will help clinicians identify individuals most likely to have experienced severe withdrawal syndromes and will aid researchers attempting to understand more about the etiology of these problems.     

Placement of Umbilical Artery Catheters High vs. Low

Placement of umbilical artery catheters was retrospectively reviewed in 181 newborns to evaluate random placement of catheter tip in the "high" position between T₇ and T₉ in the thoracic aorta of 127 infants and in the "low" position below 4 in the abdominal aorta of 54 infants. Group differences in gestational age, asphyxia, hypotension, respiratory disease, duration of catheterization, or infusate type were not significant. Cyanosis or blanching in the low extremities occurred in 67% of the "low" group and 21% of the "high" group ( P < .001). Hematuria occurred in 39% of the "low" group and 21% of the "high" group ( P < .05). High placement appears to have fewer complications. Prompt intervention by neonatal nurse practitioners can help reverse complications that occur during umbilical artery catheterizations.