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Biomedical subjects

C S Carter

Publications and source records attributed to C S Carter.

At least 19 recordsLinked to original sources

Oxytocin and social bonding.

The prairie vole is an excellent model for examining the neurobiology of social attachment, and in particular of pair-bond formation. In female prairie voles either sexual interactions or oxytocin infusions can hasten the formation of a partner preference. These results implicate oxytocin in the formation of adult heterosexual social bonds. In conjunction with work on other social systems described in this volume, these findings also support the suggestions of Klopfer and Newton that oxytocin may be important in coordinating mammalian social interactions with other critical reproductive events such as birth, lactation, and sexual behavior.

Aggression

Partner preference development in female prairie voles is facilitated by mating or the central infusion of oxytocin.

Results of these experiments indicate that females given at least 24 hours of cohabitation with a male develop a social preference for the familiar partner versus a stranger. Mating is not essential for the development of partner preferences, but clearly facilitates the onset of preferences. Females given six hours of cohabitation showed partner preferences only if they mated with the partner during cohabitation (Experiment 2) or if they received oxytocin (Experiment 3). Females that continued to mate during preference tests (Experiment 2, n = 4) mated exclusively with the partner. Oxytocin infusions, even in the absence of mating or estrogen priming, facilitated the development of partner preferences.

Animals

Attentional asymmetry in schizophrenia: controlled and automatic processes.

Two versions of Posner's covert orienting task were administered to 14 drug-free schizophrenic patients and 12 normal controls. In the schizophrenic subjects, automatic orienting to exogenous cues in the right visual field was impaired. However, this lateralizing general deficit was not present when the schizophrenics were able to direct attention effortfully in the second version of the task using endogenous cues. These findings support the hypothesis that there is a deficit in left hemispheric mechanisms mediating visual spatial attention in schizophrenia. However, when schizophrenics are given the opportunity to use an attentional strategy they are able to partially overcome this lateralized processing deficit.

Attention

Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience.

Prairie voles (Microtus ochrogaster) exhibit a monogamous mating system characterized by long-term pair bonds between mates. The purpose of this study was to examine the effect of cohabitation time and sexual experience on the development of pair bond formation in female prairie voles. Females that were allowed to cohabit for 24 hr or more, with or without mating, exhibited a strong social preference for a familiar partner versus a strange male. Females that cohabited and mated for 6 hr showed strong preferences for a familiar partner, while cohabitation for less than 24 hr, without mating, did not result in preferences for the familiar male. These results indicate that mating was not essential for partner preference formation; however, preferences developed more rapidly when mating occurred.

Aggression

Olfactory bulb removal affects partner preference development and estrus induction in female prairie voles.

In female prairie voles (Microtus ochrogaster) bilateral olfactory bulbectomy reduced affiliative behavior, as measured by social contact, and prevented the formation of partner preferences. Unilateral olfactory bulb removal did not significantly influence affiliative behavior, but did inhibit partner preferences. Bilateral, but not unilateral, bulbectomy significantly reduced the proportion of females exhibiting behavioral estrus following male exposure. In contrast to affiliative and sexual behavior, parental behavior was not significantly affected by either bilateral or unilateral olfactory bulbectomy. These results suggest that divergent sensory-neural pathways underlie social, sexual, and parental behaviors in this species.

Aggression

Abnormal processing of irrelevant information in chronic schizophrenia: selective enhancement of Stroop facilitation.

Thirteen medication-free chronic schizophrenic patients and 11 normal control subjects were administered a trial by trial version of the Stroop Color Naming Task which evaluated separately the processes of interference and facilitation. There was no difference between the groups in the amount of interference to naming the colors of color-incongruent words. However, patients with schizophrenia showed significantly greater speed in naming the colors of color-congruent words when compared with control subjects. Thus, facilitation on the Stroop Task appears to be selectively enhanced in schizophrenia. Similar findings have been recently observed in patients with Parkinson's disease. This result may indicate a selective disruption of an automatic inhibitory process in this patient group and is consistent with the hypothesis that a deficit in mesocortical dopamine projections to the frontal cortex underlies some of the cognitive deficits of chronic schizophrenia.

Adult

Oxytocin and sexual behavior.

The neurohypophyseal hormone oxytocin has been implicated in many aspects of reproduction including sexual behavior. This review considers the hypotheses that oxytocin and/or the neural events surrounding the release of oxytocin may have behavioral effects during sexual arousal, orgasm, sexual satiety and other aspects of sociosexual interactions.

Animals

Enumeration of cells in bone marrow and peripheral blood stem cell collections: technical issues and prospects for standardization.

Enumeration of total nucleated cells and mononuclear cells is a fundamental part of the laboratory evaluation and quality control program for bone marrow and peripheral blood stem cell collections intended for transplantation. Measurement of the total nucleated cell content is especially useful for providing rapid feedback about the bone marrow product during or immediately after the harvest. However, the mononuclear cell content may be more informative because the nucleated cell population contains a variable number of mature granulocytes and nucleated red cells, which do not contribute to hematopoietic engraftment. The lack of comparative data among various laboratories and among different types of cell counting methods has hindered standardization of these assays among bone marrow processing laboratories. Specific issues needing attention in assay standardization include sample preparation and handling, identification and elimination of artifacts in automated counting, relative advantages and disadvantages of manual and automated counting methods, and criteria for differential counting of nucleated cells. The establishment of standards for bone marrow and other stem cell counting methods, as well as other evaluation procedures, should be preceded by collection and analysis of comparative data, and followed by a proficiency testing program for bone marrow processing laboratories.

Artifacts

Patterns of abnormal processing of emotional information in panic disorder and major depression.

Studies showing interference with color naming threat-related words in patients with anxiety disorders suggest a bias towards processing threatening material in these patients. We assessed the specificity of this finding to anxiety disorders and to threatening stimuli by administering Stroop cards with a variety of types of emotional stimuli to 24 panic disorder patients with no history of major depression, 30 patients with major depression and no history of panic attacks and 25 controls with no history of an axis I disorder. Our findings suggest that the abnormal information processing seen in panic disorder may be characterized by a more general bias towards processing emotional stimuli than previously thought. They also suggest that this more general bias may illustrate differences in information processing in panic disorder and major depression.

Adult

Chest pain in generalized anxiety disorder.

OBJECTIVES: The objectives of the current study were to evaluate the prevalence of chest pain and related medical utilization in patients with generalized anxiety disorder and to investigate the possible relationship between the occurrence of chest pain in these patients and the episodes of excessive worry which characterize this disorder. METHOD: The presence of a history of chest pain in patients with generalized anxiety disorder was investigated in an outpatient psychiatric sample using a structured interview which also assessed related medical utilization and the relationship of chest pain to panic attacks and episodes of excessive worry. RESULTS: Of fifty sequentially evaluated patients meeting DSM-III R criteria for G.A.D., twenty-four (48%) reported a history of chest pain. Seven of these patients also had a history of panic attacks, however, four of the seven reported that their pain occurred independently of their panic attacks. Sixteen patients with G.A.D. reported that their chest pain episodes were associated with episodes of excess worry. Eleven had sought medical evaluation for their pain. Patients with chest pain and normal coronary arteries are frequently found to have panic disorder. The pattern of utilization of medical care was comparable in this sample of patients with G.A.D. and a group of patients with panic disorder recruited in a similar manner. CONCLUSIONS: These results suggest that in addition to panic disorder, G.A.D. may also be a common diagnosis in chest pain patients with no demonstrable coronary disease. Future studies of coronary artery disease negative patients with chest pain should include assessments for the presence of G.A.D. Our results also suggest that chest pain may be a common symptom in G.A.D. The possibility that chest pain should be included in the diagnostic criteria for this disorder should be the subject of further investigation.

Adult

Hyperventilation-induced panic attacks in panic disorder with agoraphobia.

Eight minutes of hyperventilation to an end-tidal PCO2 of less than 20 mmHg led to a panic attack in 7 of 12 patients with panic disorder with agoraphobia and only 1 of 12 normal controls. Patients experienced greater increases in panic symptoms than controls during hyperventilation. Patients who reported more distress from somatic symptoms of hyperventilation during the preceding week were more likely to panic during hyperventilation. Patients who panicked during hyperventilation exhibited a delayed recovery of normocapnia following hyperventilation. Hyperventilation by this protocol is an effective means of inducing panic attacks in the laboratory. A hyperventilation challenge may identify a subgroup of patients for whom hyperventilation symptoms are frequently associated with panic.

Adult

Stimulatory effect of counterflow centrifugal elutriation in large-scale separation of peripheral blood monocytes can be reversed by storing the cells at 37 degrees C.

Transfusion of peripheral blood monocytes may be of benefit as adjuvant treatment of leukopenic patients with serious infections. To study the feasibility of this approach, a large-scale monocyte separation procedure employing leukapheresis, density gradient centrifugation, and counterflow centrifugal elutriation was established. By processing 5 to 6 liters of normal donor blood, it was possible to obtain a mean of 1.1 x 10(9) (range: 0.5-1.7 x 10(9) cells) of mononuclear cells, of which 89% (range: 82-94%) were monocytes by Wright's stain morphology. When the elutriation was performed in XVIVO-10, a commercially available, serum-free medium developed for adoptive immunotherapy, spontaneous secretion of superoxide by the monocytes was significantly higher than for monocytes elutriated in Hanks' balanced salt solution without calcium and magnesium or non-elutriated peripheral blood mononuclear cells. This stimulated state of the monocytes was observed both immediately after elutriation and after overnight storage at 4 degrees C, and it was not affected by the type of storage vessel used. Overnight storage of the monocytes at 37 degrees C resulted in a reversal of the stimulated state of the cells. Monocytes elutriated in XVIVO-10 and kept overnight at 4 degrees C released high amounts of arachidonic acid. A subsequent decrease in this release was seen after additional storage at 37 degrees C for 18 hours. These observations demonstrate that separation and storage variables have important effects on the state of stimulation of monocytes. Further investigations of such variables may suggest improved procedures for preparation and storage of these cells, as well as possible ways to stimulate monocytes prior to transfusion.

Arachidonic Acid

Peripheral blood mononuclear cell collection from patients undergoing adoptive immunotherapy or peripheral blood-derived stem cell transplantation and from healthy donors.

The demand for collection of mononuclear cells from the peripheral blood of patients for therapeutic purposes is rapidly increasing. Automated blood cell separators are usually designed for collection of blood components from healthy donors. We reviewed safety and efficiency of collection data of a new procedure for the Fenwal CS 3000 blood cell separator in 125 collections from normal donors and 101 collections from patients after IL-2 pretreatment or chemotherapy. The new procedure set red blood cell spillovers to occur at 3.5 minute intervals, using procedure 1 with the interface detector set at 1,000 and the standard granulocyte and collection chambers. Despite significant anemia and thrombocytopenia in a large number of patients no serious procedure-related side effects occurred. The lymphocyte yield was 4.74 +/- 1.6 x 10(9) per 5 liters of blood processed in normal donors and 24.2 +/- 12.0 x 10(9) per 10 liters of blood processed after IL-2 treatment. After chemotherapy the lymphocyte yield was 4.5 +/- 3.1 x 10(9) per 10 liters of blood processed; the collection efficiency was found to be significantly lower in this group. The main problem was the platelet loss of 35.6 +/- 12% of the initial count in normal donors, 40.3 +/- 14.1% after IL-2 treatment, and 42.1 +/- 18.0% after chemotherapy. The platelet loss is, however, closely related to the preapheresis platelet count; patients with thrombocytopenia lose fewer platelets than normal donors. Therefore the procedure was found to be safe for patients with a platelet count as low as 20/nl. This report provides a basis for safe, effective mononuclear cell collection from patients with very abnormal peripheral blood counts.

Adolescent

Testosterone therapy is associated with reduced tactile sensitivity in human males.

Responses to vibrotactile stimuli were examined in men as a function of chronic exposure to either exogenous or endogenous androgens. Psychophysical techniques were used to evaluate thresholds to stimulus detection and perceived stimulus intensities in response to mild vibration applied to either the finger or the penis. Normal men were compared to the following groups: (a) untreated hypogonadal men, (b) androgen-replaced hypogonadal men, or (c) infertile men with androgen levels in the low normal range. Among the four groups, untreated hypogonadal men perceived vibrotactile stimuli as most intense and were slightly more sensitive to touch than were men with higher levels of androgen. Chronic treatment with testosterone enanthate was associated with a decline in the perceived intensity of vibrotactile stimuli in hypogonadal men. The lowest levels of sensitivity to tactile stimuli were observed in the infertile men.

Adult

Absence of modulation of monokine production via endogenous cyclooxygenase or 5-lipoxygenase metabolites: MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2- dimethylpropanoic acid), indomethacin, or arachidonate fail to alter immunoreactive interleukin-1 beta, or TNF-alpha production by human monocytes in vitro.

Human peripheral blood monocytes exposed to MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2- dimethylpropanoic acid) at doses which abolish formation of 5-lipoxygenase metabolites showed unaltered interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) levels in response to phorbol ester, concanavalin A, serum-treated zymosan, or lipopolysaccharide. Indomethacin (10 microM), alone or in combination with MK-886, also failed to modulate monokine production in response to any stimulus. Exogenous arachidonate (3-30 microM) which augmented the formation of PGE2 and LTB4 in the absence of stimulation, also had no effect on monokine production. LPS-induced IL-1 and TNF production occurred despite stimulation of PGE2 synthesis. The results make a role for endogenous prostaglandins and leukotrienes in the regulation of monocyte IL-1 beta and TNF-alpha production unlikely. These data also indicate that MK-886, a novel inhibitor of 5-lipoxygenase product formation, is a potentially useful leukotriene inhibitor which does not affect monokine production.

Analysis of Variance

Oxytocin inhibits male sexual behavior in prairie voles.

Intracerebroventricular (ICV) injection of oxytocin (300 ng) produced an immediate cessation in sexual behavior in sexually active male prairie voles (Microtus ochrogaster). Other social behaviors including social contact, aggression, and autogrooming were not significantly affected by oxytocin, but males that received oxytocin ICV, versus injections that missed the ventricles, showed more sleep postures. Sexual behavior remained inhibited for at least 24 hours and was not activated in tests with a novel receptive female. Sexual and social behavior were not significantly altered in animals in which the oxytocin injection missed the ventricles or in saline-treated males. These findings are consistent with the hypothesis that oxytocin plays a role in sexual satiety.

Animals

Female-female interactions and social stress in prairie voles.

Trios of prairie voles (Microtus ochrogaster) composed of either two estrous sibling or nonsibling females and one male were monitored via time-lapse videotaping over 72 hr. Social and sexual behaviors were analyzed as a function of trio type (sibling or nonsibling) and fate (survivor or nonsurvivor) across 12-h time blocks. Within nonsibling trios, females that were able to maintain prolonged physical contact with the male within the first 3 days of trio formation later survived and successfully produced litters; females that did not maintain male contact later died of undetermined causes, presumably related to social stress. Frequencies of sexual behavior were similar in both trio types and both surviving and nonsurviving females received equivalent amounts of copulatory stimulation from the male. Sibling groups exhibited higher levels of female-female side-by-side contact; nonsibling groups exhibited greater amounts of female-initiated anogenital sniffing, and female-initiated aggression. Female-female social interactions may be determined by prior familiarity and/or relatedness and may play a dominant role in determining the social organization and mating system of this species.

Animals

Elevated serum lactate associated with panic attacks induced by hyperventilation.

Several lines of evidence suggest that lactate metabolism may be altered in panic disorder. We recently reported exaggerated increases in serum lactate in panic patients following hyperventilation during glucose infusion. In the current study, lactate metabolism was stimulated by hyperventilation following glucose ingestion in 12 panic patients and 12 controls. The seven patients who panicked during hyperventilation exhibited larger increases in serum lactate levels than nonpanicking patients or controls. The lactate response was significantly correlated with peak ratings of anxiety and panic symptoms, but not correlated with insulin or cortisol levels, heart rate, pCO2, adiposity, exercise habits, or diet. Hyperventilation-induced panic appears to be associated with metabolic changes leading to elevated serum lactate.

Adult