Ontogeny of mitogen responsive lymphocytes in the bovine fetus

Bovine fetal lymphocytes were examined for their ability to respond to the mitogens phytohemagglutinin (PHA), Concanavalin A (ConA) and pokeweed mitogen (PWM) in the lymphocyte blastogenesis test (LBT). PHA-, Con A- and PWM-responsive lymphocytes appeared simultaneously at 75-80 days of gestation. The response increased with age of the fetus until, by 120 days of gestation, the response to PHA, Con A and PWM of many fetuses was in the range of values obtained with lymphocytes from normal adult cattle.     

Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions

1. This study investigates the behavioral conditions in which dopamine (DA) neurons of substantia nigra and adjoining areas A8 and A10 respond with impulses to visual and auditory trigger stimuli eliciting immediate arm- and eye-movement reactions. 2. In a formal task, the rapid opening of the door of a small, food-containing box located at eye level ahead of the animal served as visible and audible trigger stimulus. Most DA neurons on the contralateral side responded to this stimulus with a short burst of impulses with median onset latency of 50 ms and duration of 90 ms (75% of 164 neurons). Similar responses were seen in a comparable fraction of DA neurons during ipsilateral task performance, suggesting that responses were not specific for the limb being used. 3. When the sensory components of the door opening stimulus were separated, DA neurons typically responded in a similar manner to the moving visual stimulus of the opening door, the low-intensity sliding noise of the opening door, and the 1-kHz sound of 90-92 dB intensity emitted from a distant source at the onset of door opening. Responses to each component alone were lower in magnitude than to all three together. 4. In a variation of the task, a neighboring, identical food box opened in random alternation with the other box but without permitting animals to reach out (asymmetric, direct-reaction go/no-go task). With each sensory component, DA neurons typically responded both to opening of go and no-go boxes. Responses were enhanced when stimuli elicited limb movements in go trials. 5. Monkeys reacted to door opening with target-directed saccadic eye movements in the majority of both go and no-go trials. Neuronal responses were equally present during the occasional absence of eye movements. Thus responses were not specific for the initiation of individual arm or eye movements. 6. Neuronal responses were absent when the same stimuli occurred outside of the behavioral task with target-direct arm and eye movements lacking. This shows that responses were not of purely sensory nature but were related to the capacity of the stimulus for eliciting behavioral reactions. 7. In a variation of the go/no-go task, an instruction light illuminated 2-3 s before door opening prepared the animal to perform the reaching movement on door opening or to refrain from moving (asymmetric, instruction-dependent go/no-go task).(ABSTRACT TRUNCATED AT 400 WORDS)     

β-Adrenergic receptors in rat cerebellum after neonatal X-irradiation: Effect of prolonged imipramine and lithium treatment

The actions of prolonged treatment of rats within imipramine or lithium chloride on the β-adrenergic cAMP generating system of the cerebellum were compared in normal animals and in rats degranulated by neonatal X-irradiation. Whereas in normal animals imipramine treatment is without significant effect on the cerebellar cAMP system but lowers the β-adrenoceptor density significantly, in degranulated animals the cAMP system becomes subsensitive towards norepinephrine after prolonged imipramine treatment. These data support the hypothesis that in the cerebellum imipramine acts predominantly on β-adrenoceptors located particularly on Purkinje cells. Prolonged lithium treatment exhibited no significant effects on β-receptors nor the noradrenergic cAMP generating system of normal and degranulated cerebella.     

Dental abnormalities in individuals with pathogenic germline variation in DICER1

Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor‐predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unknown. DICER1‐carriers (n = 57) and family controls (n = 55) were evaluated at the NIH Clinical Center dental clinic as part of a comprehensive medical evaluation. Digital panoramic radiographs, bite‐wing radiographs, and oral photographs were collected. A single observer, blind to DICER1 status, reviewed the dental records and determined the presence or absence of 11 dental characteristics as described in the clinic notes, radiographs, or oral photographs. Subjective phenotypes were reviewed on radiographs by two examiners (blind to DICER1 status) for the presence or absence of the dental characteristics to reduce inconsistencies. By simple association, bulbous crown, periodontitis, and taurodontism were all significant (p < .05). Logistic regression with chi‐square maximum likelihood estimates showed that bulbous crown and periodontitis remained significant. Recognition of these phenotypes may aid identification of individuals and families at risk for DICER1‐associated neoplasms. These findings may also guide dental care for individuals with germline DICER1 pathogenic variation.     

A de novo X;3 translocation in Rett syndrome

Rett syndrome is a neurodegenerative disorder that occurs exclusively in females. The syndrome is sporadic in most cases with the exception of a few familial cases with an inheritance pattern through maternal lines. These observations raised the possibility that Rett syndrome may be due to an X-linked dominant mutation which is lethal in the male. To evaluate this hypothesis, we have systematically performed high-resolution chromosome analysis on 28 patients with Rett syndrome searching for deletions and/or translocations. In one patient, a de novo balanced translocation was observed with the chromosome constitution of 46,X,t(X;3) (p22.11;q13.31). This finding supports the hypothesis of an X-linked dominant mutation and suggests that the Rett gene might map to distal Xp21 or proximal Xp22.     

Natural and immune cytolysis of canine distemper virus-infected target cells.

Natural and immune cytolysis of canine distemper virus (CDV)-infected target cells in vitro is described. Lymphocytes expressing natural cytotoxicity were found in specific-pathogen-free beagle dogs and in beagle-coonhound crosses before vaccination with CDV and indefinitely after vaccination, when the ephemeral immune lymphocyte-mediated cytotoxicity (ILMC) had declined. In contrast to the natural lymphocyte-mediated cytotoxicity, the ILMC was genetically restricted, could not be blocked by CDV-specific antibody, and was effective against measles virus-infected as well as CDV-infectd target cells. Lymphocyte populations were depleted of Fc receptor and surface immunoglobulin-bearing cells by rosetting techniques and tested in comparison. An antibody-dependent cell-mediated cytotoxicity was demostrated against CDV-infected target cells that were preincubated with CDV antibody when Fc receptor-bearing lymphocytes were not removed. The ILMC was measurable for approximately 10 days beginning at 6 days post-vaccination. In contrast, CDV antibody measured by virus neutralization and humoral cytotoxicity was detectable by 6 days postvaccination and persisted at peak levels for at least 5 months.     

The biopsychosocial approach: Clinical examples from a consultation-liaison service

In this second of three articles exploring Engel's biopsychosocial model, five case histories illustrate how psychological factors, sometimes related to organic trauma or illness, may precipitate psychiatric conditions. The patients’ disorders, and their management by a consultation-liaison team, demonstrate the interaction of biologic, psychological, and social systems in assessment and treatment of disease.     

Reward-related neuronal activity during go-nogo task performance in primate orbitofrontal cortex

The orbitofrontal cortex appears to be involved in the control of voluntary, goal-directed behavior by motivational outcomes. This study investigated how orbitofrontal neurons process information about rewards in a task that depends on intact orbitofrontal functions. In a delayed go-nogo task, animals executed or withheld a reaching movement and obtained liquid or a conditioned sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed (movement vs. nonmovement) and the reinforcer to be obtained (liquid vs. sound) after a subsequent trigger stimulus. We found task-related activations in 188 of 505 neurons in rostral orbitofrontal area 13, entire area 11, and lateral area 14. The principal task-related activations consisted of responses to instructions, activations preceding reinforcers, or responses to reinforcers. Most activations reflected the reinforcing event rather than other task components. Instruction responses occurred either in liquid- or sound-reinforced trials but rarely distinguished between movement and nonmovement reactions. These instruction responses reflected the predicted motivational outcome rather than the behavioral reaction necessary for obtaining that outcome. Activations preceding the reinforcer began slowly and terminated immediately after the reinforcer, even when the reinforcer occurred earlier or later than usually. These activations preceded usually the liquid reward but rarely the conditioned auditory reinforcer. The activations also preceded expected drops of liquid delivered outside the task, suggesting a primary appetitive rather than a task-reinforcing relationship that apparently was related to the expectation of reward. Responses after the reinforcer occurred in liquid- but rarely in sound-reinforced trials. Reward-preceding activations and reward responses were unrelated temporally to licking movements. Several neurons showed reward responses outside the task but instruction responses during the task, indicating a response transfer from primary reward to the reward-predicting instruction, possibly reflecting the temporal unpredictability of reward. In conclusion, orbitofrontal neurons report stimuli associated with reinforcers are concerned with the expectation of reward and detect reward delivery at trial end. These activities may contribute to the processing of reward information for the motivational control of goal-directed behavior.     

Hydrolytic Polycondensation of Bisphenol‐A‐Bischloroformate Catalyzed by Phase‐Transfer Catalysts

The hydrolytic interfacial polycondensation of bisphenol‐A‐bischloroformate was performed with four different phase‐transfer (PT) catalysts: N‐butylpyridinium bromide, triethylbenzylammonium (TEBA) chloride, tetrabutylammonium hydrogen sulfate, and tetraphenylphosphonium bromide. These polycondensations were conducted at 5 or 35 °C initial reaction temperature. The resulting polycarbonates were characterized by viscosity and SEC measurements and by MALDI‐TOF mass spectrometry. The four PT catalysts gave quite different results with respect to molecular weight and formation of cyclic polycarbonates. The highest molecular weights (number average, and weight average, ) were obtained with TEBA‐Cl. Lower temperatures and high feed ratios of TEBA‐Cl proved to be favorable for both high molecular weights and high fractions of cycles. Cyclic polycarbonates were detectable in the mass spectra up to 14 kDa (technical limit of the measurements). Low molecular weights in combination with unreacted chloroformate groups proved that the other PT‐catalysts were less efficient under the given reaction conditions.

MALDI‐TOF mass spectrum of the polycarbonate No. 3b .     

Comparison of the working formulation of non-Hodgkin's lymphoma with the Rappaport, Kiel, and Lukes & Collins classifications. Translational value and prognostic significance based on review of 658 patients treated at a single institution

Six hundred fifty-eight cases of previously untreated non-Hodgkin's lymphoma seen between 1970 and 1979 at the Medical Department, the Finsen Institute, were the basis for a comparative study of the prognostic value of the Rappaport, Kiel, and Lukes & Collins classifications and the new translation system, the Working Formulation of Non-Hodgkin's Lymphoma. Each histopathologic system proved equally effective in separating patients into subgroups with a spectrum of prognoses ranging from a median survival of less than 1 year to greater than 7 years. The established classifications were compared with the Working Formulation in order to evaluate its translational value. The Working Formulation was more similar to the Rappaport and the Lukes & Collins systems than to the Kiel system, since 82%, 89%, and 75% of the cases, respectively, were translatable following the guidelines outlined in the National Cancer Institute (NCI)-sponsored study. Similarities among the four systems were demonstrated in lymphomas with follicular growth pattern, and in diffuse lymphomas composed of small mature appearing lymphocytes or small cleaved lymphocytes. Incongruity among the systems was more marked in lymphomas composed of large lymphoid cells or in lymphomas of mixed cellular composition. A comparison was performed for each classification against the Working Formulation. All such subdivided subsets were tested for prognostic heterogeneity and the following conclusions were reached: the diffuse poorly differentiated lymphocytic category of Rappaport was separated into two subgroups (malignant lymphoma [ML] small cleaved cell and ML lymphoblastic) with different prognoses (P = 0.01); the diffuse "histiocytic" lymphomas were prognostically homogeneous, since none of the newer systems were able to identify subpopulations with significantly different prognoses; the subtypes of the Kiel classification were prognostically homogeneous; the only weakness of the Lukes & Collins classification was the undefined cell subtype, encompassing two populations with different prognoses; and (5) the importance of follicular growth pattern was confirmed for small cleaved cell and mixed cell cytology, whereas large cell cytology implied a poor prognosis regardless of pattern. By the use of the Cox regression model it could be demonstrated that the Working Formulation can substitute any of the established classifications in terms of prognostic value.