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 role of anterior ectosylvian cortex in cross-modality orientation and approach behavior

Physiological and behavioral studies in cat have shown that corticotectal influences play important roles in the information-processing capabilities of superior colliculus (SC) neurons. While corticotectal inputs from the anterior ectosylvian sulcus (AES) play a comparatively small role in the unimodal responses of SC neurons, they are particularly important in rendering these neurons capable of integrating information from different sensory modalities (e.g., visual and auditory). The present experiments examined the behavioral consequences of depriving SC neurons of AES inputs, and thereby compromising their ability to integrate visual and auditory information. Selective deactivation of a variety of other cortical areas (posterolateral lateral suprasylvian cortex, PLLS; primary auditory cortex, AI; or primary visual cortex, 17/18) served as controls. Cats were trained in a perimetry device to ignore a brief, low-intensity auditory stimulus but to orient toward and approach a nearthreshold visual stimulus (a light-emitting diode, LED) to obtain food. The LED was presented at different eccentricities either alone (unimodal) or combined with the auditory stimulus (multisensory). Subsequent deactivation of the AES, with focal injections of a local anesthetic, had no effect on responses to unimodal cues regardless of their location. However, it profoundly, though reversibly, altered orientation and approach to multisensory stimuli in contralateral space. The characteristic enhancement of these responses observed when an auditory cue was presented in spatial correspondence with the visual stimulus was significantly degraded. Similarly, the inhibitory effect of a spatially disparate auditory cue was significantly ameliorated. The observed effects were specific to AES deactivation, as similar effects were not obtained with deactivation of PLLS, AI or 17/18, or saline injections into the AES. These observations are consistent with postulates that specific cortical-midbrain interactions are essential for the synthesis of multisensory information in the SC, and for the orientation and localization behaviors that depend on this synthesis.     

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.     

Detection of multiple macrolide- and lincosamide-resistant strains of Streptococcus pyogenes from patients in the Boston area

Macrolide (including erythromycin and azithromycin) and lincosamide (including clindamycin) antibiotics are recommended for treatment of penicillin-allergic patients with Streptococcus pyogenes pharyngitis. Resistance to erythromycin in S. pyogenes can be as high as 48% in specific populations in the United States. Macrolide and lincosamide resistance in S. pyogenes is mediated by several different genes. Expression of the erm(A) or erm(B) genes causes resistance to erythromycin and inducible or constitutive resistance to clindamycin, respectively, whereas expression of the mef(A) gene leads to resistance to erythromycin but not clindamycin. We studied the resistance of S. pyogenes to erythromycin and clindamycin at an urban tertiary-care hospital. Of 196 sequential isolates from throat cultures, 15 (7.7%) were resistant to erythromycin. Three of these were also constitutively resistant to clindamycin and had the erm(B) gene. Five of the erythromycin-resistant isolates were resistant to clindamycin upon induction with erythromycin and had the erm(A) gene. The remaining seven erythromycin-resistant isolates were susceptible to clindamycin even upon induction with erythromycin and had the mef(A) gene. Pulsed-field gel electrophoresis analysis and emm typing demonstrated that the erythromycin-resistant S. pyogenes comprised multiple strains. These results demonstrate that multiple mechanisms of resistance to macrolide and lincosamide antibiotics are present in S. pyogenes strains in the United States.     

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.