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Background Few studies have examined the impact of abdominoplasty on chronic back pain. Objectives The aim of this study was to test our hypothesis that patients undergoing abdominoplasty with anterior abdominal wall plication will show significant improvements in back pain and physical function compared with those without plication. Methods We utilized Current Procedural Terminology (CPT) codes to identify patients who underwent abdominoplasty with the senior author over a 10-year period. The Oswestry Disability Index (ODI) and the RAND 36-Item Short-Form Health Survey (SF-36) were administered. All patients indicating preoperative back pain were reviewed. Results Of 338 patients, 143 surveys (42.3%) were returned; 51 patients (35.7%; n = 28 aesthetic, n = 23 massive weight loss) reported preoperative back pain on the ODI. Paired t tests compared overall and strata-specific changes in ODI and SF-36 pre- and postsurgery. Multivariable linear regression models were fitted to model relations between scores and plication, adjusting for presurgery scores and patient variables. There were significant improvements in overall patient cohort in ODI (–15.14), SF-36 physical function (19.92), and pain (17.42) (P Conclusions Abdominoplasty with and without anterior abdominal wall plication significantly improves ODI and SF-36 scores relating to physical function and pain, in both aesthetic and massive weight loss patients. Outcomes did not differ based on plication status. All patients with preoperative back pain showed improvement regardless of operation performed, suggesting that abdominoplasty with or without abdominal wall plication improves chronic back pain in this patient population. Level of Evidence: 4

Background: Incidence of chronic Graft-versus- Host Disease (cGvHD) is ~45%, but varies significantly depending on conditioning regimen, choice of donor, stem cell source, age and GvHD prophylaxis. In the past, increasing cGvHD incidence was reported due to accumulation of risk factors, but recent studies capturing the effect of new prophylaxis strategies are lacking. Methods: This study was conducted as joint analysis of 308 patients from two cohorts – cohort 1 included patients (pts) transplanted 2017 at University Hospital Zagreb (Croatia), and St. Anna Children`s Hospital, Vienna (Austria), cohort 2 included consecutive pts documented in period from July 2015 to September 2018 within the German- Austrian-Swiss GvHD register. Results: Cohort 1 consisted of 98 (55% male), mainly adult pts (70%), who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) at median age of 40 (range 0-66) years, and cohort 2 out of 210 (65% male) pts transplanted at median age of 56 (range 19-70) years. Most frequent indications for alloHSCT in both cohorts were acute leukaemia (51.9%), myelodysplastic/myeloproliferative diseases (19.2%), lymphoma (15.6%), plasma cell disorders (5.5%), non-malignant diseases (7.2%), and solid tumours (0.7%). 65% of all alloHSCT were performed from unrelated donors, 23% from matched related donors and 12% from haploidentical donors (25% in cohort 1 vs. 6% in cohort 2). Peripheral blood stem cells were applied in 73%, while 27% received bone marrow grafts. For both cohorts, at median follow-up of 333 (range 0-1149) days, the overall survival (OS) was 71% and cumulative incidence (CI) of treatment related mortality (TRM) 19%. CI of malignant disease relapse was 21%, and occurred at median of 154 (range 0-757) days after alloHSCT. Acute GvHD was reported with CI of 42% (6% for stage III/IV) in period of 100 days. For cohort 1 late acute GvHD had CI of 10% (1% for stage III/IV) and occurred at median time of 166 (range 110-424) days after alloHSCT and for cohort 2 CI was 11% (3% for stage III/IV) and occurred at median time of 217 (range 106-562) days. In cohort 1 CI of cGvHD was 14% and all pts had NIH moderate/severe global score at onset which occurred at median of 197 (range 62-700) days with de novo, progressive and quiescent onset in 42%, 25% and 33%, respectively. In cohort 2 CI of cGvHD was 39% (19% moderate/severe) at onset at median of 197 (range 92-588) days with de novo, progressive and quiescent onset in 37%, 1% and 62%, respectively. Four pts of cohort 2 were diagnosed with cGvHD with other manifestations such as glomerulonephritis or cerebral vasculitis. Among cGvHD pts from cohort 1 most involved organs at onset were mouth (82%), skin (73%), and eyes (64%) followed by liver (55%), gastrointestinal tract and lung (each 27%) and genital tract (18%) with a median Karnofsky/Lansky score of 80% (range 50-100). In the joint analysis, 71% pts required second line treatment. Conclusions: This study shows for the first time a decreasing incidence of cGvHD compared to previous publications which may reflect the change in practice pattern in prophylaxis and treatment of GvHD

Nearly stoichiometric chromium carbide thin films (Cr3C2) were deposited by unbalanced r.f. magnetron sputtering of a chromium carbide target in a pure argon discharge. Their microstructure and hardness are shown to be strongly influenced by the working pressure and substrate bias during deposition. Further correlation with the plasma parameters, i.e. the energy and flux of argon ions as well as the flux of film-forming particles, is illustrated, which indicates the momentum transferred by bombarding ions per film-forming particle Pdens which creates a densification and simultaneously does not cause a mobility enhancement to be dominant for the film structure. Below a threshold value of Pdens of about 0.91 u0.5eV0.5, the resulting films exhibited an amorphous structure with a relatively low hardness of 1200 HV0.02. A nanocrystalline structure emerged only for larger values of Pdens, and was responsible for a hardness enhancement to 3500 HV0.02.

jerne suggested that a quintessentialfeature of the immune system was the recognition of self-idiotypes 1,2 . Despite intense interest and investigation, the concept remains a hypothesis. Here the authors discuss data which place in question the necessity of an idiotype network.

We evaluated the effect of specimen processing variations and quantitation methods on quantitative determination of CD38 expression on CD8 T lymphocytes. Neither lysing reagent (ammonium chloride versus BD FACSlyse), fixation (paraformaldehyde versus no final fixation step), nor acquisition delay (acquisition within 6 h after fixation versus 24 h after fixation) had a significant effect on CD38 relative fluorescent intensity or CD38 quantitative estimates (RFI or antibodies bound per cell). The only significant difference in fluorescent intensity and CD38 antibodies bound per cell (ABC) was encountered when whole blood was held for 24 h prior to staining and fixation and then acquired after another 24-h hold. However, for all sample processing methods above, the CD4 biologic calibrator and QuantiBRITE bead methods gave significantly different estimates of CD38 intensity. In many cases, however, these differences are relatively small and were more pronounced in certain laboratories. We conclude that there is some flexibility in sample processing methods for quantitative CD38 determination; however, it is preferable for a laboratory to employ one method of fluorescence quantitation calculation consistently because small differences are detected between different methods. Cytometry (Comm. Clin. Cytometry) 42:174–179, 2000. © 2000 Wiley-Liss, Inc.

The proliferative capacity of T cells infiltrating human tumors is known to be impaired, possibly through their interaction with tumor. Here we demonstrate that soluble products derived from renal cell carcinoma (RCC-S) explants but not normal kidney can inhibit an IL-2-dependent signaling pathway that is critical to T cell proliferation. A major target of the immunosuppression was the IL-2R-associated protein tyrosine kinase, Janus kinase 3 (Jak3). RCC-S suppressed basal expression of Jak3 and its increase following stimulation with anti-CD3/IL-2. Jak3 was most sensitive to suppression by RCC-S; however, reduction in expression of p56(lck), p59(fyn), and ZAP-70 was observed in some experiments. Expression of other signaling elements linked to the IL-2R (Jak1) and the TCR (TCR-zeta, CD3-epsilon, and phospholipase C-gamma) were minimally affected. In naive T cells, RCC-S also partially blocked induction of IL-2R alpha-, beta- and gamma-chain expression when stimulating via the TCR/CD3 complex with anti-CD3 Ab. To determine whether RCC-S suppressed IL-2-dependent signaling, primed T cells were employed since RCC-S had no effect on IL-2R expression but did down-regulate Jak3 expression and, to a lesser degree, p56(lck) and p59(fyn). Reduction in Jak3 correlated with impaired IL-2-dependent proliferation and signal transduction. This included loss of Jak1 kinase tyrosine phosphorylation and no induction of the proto-oncogene, c-Myc. These findings suggest that soluble products from tumors may suppress T cell proliferation through a mechanism that involves down-regulation of Jak3 expression and inhibition of IL-2-dependent signaling pathways.

The development of tumor metastasis requires direct adhesive interactions between tumor cells and vascular endothelium. We examined the adherence of renal cell carcinoma (RCC) lines to endothelium after stimulation with different cytokines that induce expression of the vascular adhesion molecules endothelial leukocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1,Human umbilical vein endothelial cells (HUVEC) were used to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium. Expression of cell adhesion molecules (CAM) on HUVEC and RCC lines was measured with immunoflowcytometry.Stimulation of HUVEC with rIl-1 beta, rTNF-alpha, or PMA resulted in a time-dependent 1.4- to 2.9-fold increase of RCC adhesion to HUVEC. Significant increased tumor cell binding was observed after 4 hours and paralleled the time-dependent induction of ELAM-1 and VCAM-1. Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4 on RCC, and blocking studies with monoclonal antibodies directed against tumor cell-endothelial interactions mediated by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X demonstrated marked inhibition of tumor cell adherence to cytokine-stimulated HUVEC.This study demonstrates that cytokine-induced increases in RCC adherence to HUVEC are mediated in part by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X interactions and suggest that these molecules may play an important role in the ability of RCC to metastasize.

The therapeutic and biologic effects of murine monoclonal antibodies in patients with malignancies have been widely investigated. Attempts to enhance results by combining these agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m2/day 1-5, 8-12), an antibody that binds to the ganglioside GD3 present on melanoma cells, administered in combination with cisplatin (120 mg/m2) and WR-2721 (740 mg/m2) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients receiving only cisplatin and WR-2721. No significant enhancement of natural killer, lymphokine-activated killer, and antibody-dependent cellular cytotoxicity lytic activity or significant changes from baseline in lymphocyte subsets secondary to R24 were seen. In 4 of 10 patients tumor localization of mouse monoclonal antibody was found and appeared greatest at higher R24 doses and during week 1 of therapy. Human anti-mouse antibody responses developed by day 22 in 17 of 19 patients treated with R24, and the coadministration of cisplatin did not appear to abrogate this response. Finally, the half-life and Cmax of cisplatin were not affected by R24. In summary, the combination was well tolerated, responses were few, and significant biologic interactions or immunomodulation were not observed.

Amorphous and polycrystalline multilayer structures containing materials with metallic (Cr, Cr 3 C 2 ), ionic (Al 2 O 3 ) and covalent (SiC) bonding have been prepared by magnetron sputtering and ion plating in a dual-source apparatus. Up to 1000 layers have been deposited with a constant total thickness of 2.3 μm. Below a single-layer thickness of 10–30 nm the mechanical properties stress and hardness show strong variations. On one hand it is possible that below a certain thickness the mechanical properties of a single layer change (A. Pan and J.E. Greene, Thin Solid Films, 78 (1981) 25–34). On the other hand electrical resistance and electron spin density measurements indicate that electronic effects may be involved. An attempt is made to explain the observed correlations by transport mechanisms of the electrons, by saturation of dangling bonds with delocalized electrons and by changes in the electronic band structure.

The role of D1 and D2 dopamine (DA) receptor subtypes in mediating DAergic modulation of affective defense behavior in the cat has been investigated in the present study. Feline affective defense, characterized mainly by autonomic arousal, ear retraction, hissing and paw striking, was elicited by electrical stimulation of the ventromedial hypothalamus. Following the establishment of a stable threshold current for eliciting the hissing response of the behavior, the effect of systemic (IP) administration of various DAergic agonists and antagonists on the hissing threshold was determined. The injection of the nonselective DA agonist apomorphine (1.0, 0.3 and 0.1 mg/kg) facilitated hissing in a dose-related manner. This effect was mimicked by the D-2 selective agonist LY 171555 (0.1, 0.03 and 0.01 mg/kg) but not by the D1-selective agonist SKF 38393 (1.0, 5.0 and 10.0 mg/kg), and was blocked by the nonselective and the D2-selective antagonists haloperidol (0.1 and 0.5 mg/kg) and spiperone (0.2 mg/kg), respectively. The D1-selective antagonist SCH 23390 blocked apomorphine-induced facilitation only at a high dose (0.5 mg/kg). In addition, the injection of haloperidol (1.0 mg/kg), spiperone (0.2 mg/kg) or SCH 23390 (0.1 mg/kg) alone inhibited the behavior. It was therefore concluded that DAergic facilitation of affective defense behavior is mainly mediated by the D2 receptors, but that activation of the D1 receptors may play a "permissive" role. The interaction between the D1 and D2 receptors in mediating this facilitation and the behavioral specificity of the effect are discussed.

Allogeneic hematopoietic stem cell transplantation (SCT) is a well-established treatment modality for malignant and nonmalignant hematologic diseases. High-dose radio- and/or chemotherapy eradicate the hematopoietic system of the patient and induce sufficient immunosuppression to enable donor stem cell engraftment. The replacement of the recipient's immune system with that of the donor significantly contributes to the success of this treatment, since donor immune cells facilitate stem cell engraftment, provide protection from infections, and eliminate residual malignant or nonmalignant host hematopoiesis, thereby protecting from disease relapse in patients transplanted for leukemia or lymphoma (graft-versus-leukemia effect, GVL). Mediators of these beneficial effects are mature T cells within the stem cell graft. However, donor T cells can also attack host tissues and induce a life-threatening syndrome called graft-versus-host disease (GVHD). The challenge of allogeneic SCT is to find a balance between beneficial and harmful T cell effects, which at present is only insufficiently achieved by the use of immunosuppressive drugs. In the future, it might be possible to replace or support such medications by using the intrinsic regulatory capacity of the transplanted immune system, as represented by T cell subpopulations with suppressive activity, such as CD4+ CD25+ regulatory T (Treg) cells. In various mouse model systems, these cells have been shown to suppress GVHD while preserving the GVL effect. As the characterization of their human counterparts is rapidly progressing, their application in allogeneic SCT might soon be explored in clinical trials.

We evaluated the effect of specimen processing variations and quantitation methods on quantitative determination of CD38 expression on CD8 T lymphocytes. Neither lysing reagent (ammonium chloride versus BD FACSlyse), fixation (paraformaldehyde versus no final fixation step), nor acquisition delay (acquisition within 6 h after fixation versus 24 h after fixation) had a significant effect on CD38 relative fluorescent intensity or CD38 quantitative estimates (RFI or antibodies bound per cell). The only significant difference in fluorescent intensity and CD38 antibodies bound per cell (ABC) was encountered when whole blood was held for 24 h prior to staining and fixation and then acquired after another 24-h hold. However, for all sample processing methods above, the CD4 biologic calibrator and QuantiBRITE bead methods gave significantly different estimates of CD38 intensity. In many cases, however, these differences are relatively small and were more pronounced in certain laboratories. We conclude that there is some flexibility in sample processing methods for quantitative CD38 determination; however, it is preferable for a laboratory to employ one method of fluorescence quantitation calculation consistently because small differences are detected between different methods. Cytometry (Comm. Clin. Cytometry) 42:174-179, 2000.

Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in kappa B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of kappa B activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to kappa B/Rel family proteins, the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 (p50) subunit. The second abnormality in kappa B-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-kappa B complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli.

The role of the dopaminergic innervation of the medial preoptic-anterior hypothalamus (mPO-AH) in regulating the expression of affective defense behavior in the cat has been investigated in the present study. Feline affective defense behavior, characterized mainly by autonomic arousal, ear retraction, growling, hissing and paw striking, was elicited by electrical stimulation of the ventromedical hypothalamic nucleus (VMH). Following the establishment of a stable threshold current for eliciting the hissing response of the behavior, the effect of injecting various DAergic agonists and antagonists into the mPO-AH on the hissing threshold was determined. The microinjection of the non-selective DA agonist apomorphine (0.03, 0.16, 0.33, 0.66, 1.56 and 3.3 nmol) into the mPO-AH facilitated hissing in a time- and dose-dependent manner. This effect was mimicked by the D2-selective agonist LY 171555 (0.2 and 1.0 nmol) but not by the D1-selective agonist SKF 38393 (1.7 and 17 nmol), and was blocked by the non-selective and the D2-selective antagonists haloperidol (1.3 nmol) and sulpiride (14.5 nmol), respectively. The injection of the D1-selective antagonist SCH 23390 (0.3 nmol), however, did not inhibit apomorphine-induced facilitation of hissing. In addition, the injection of haloperidol (1.3 nmol) and sulpiride (14.5 nmol), but not SCH 23390 (0.3 nmol), alone inhibited the behavior. It was therefore concluded that dopaminergic stimulation of the mPO-AH may facilitate the expression of affective defense behavior in the cat via a D2 receptor-mediated mechanism. The physiological significance of this effect and the interaction between dopaminergic, noradrenergic and serotonergic innervation of the mPO-AH in modulating the expression of affective defense behavior in response to threatening stimuli are discussed.

Previously we showed that IL2 expanded tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma mediated non-major histocompatibility complex-restricted cytotoxicity. Phenotypic analysis showed that cultured TILs were composed mostly of T-lymphocytes with varying numbers of CD4+, CD8+, and CD56+ (Leu19+) populations. Here we compared the cytolytic activity of the two predominant TIL subsets, CD3+CD4+ and CD3+CD8+, to that of the CD56+ populations. Using magnetic beads coated with antibodies to either CD4 or CD8, CD3+CD4+, and CD3+CD8+ TILs were isolated in a highly enriched form (greater than 92%) and could be expanded for over 40 days in vitro with 1000 units/ml IL2. In a 4-h 51Cr release assay the CD4+ and CD8+ TILs showed minimal lytic activity, whereas unseparated cells exhibited significant levels of non-major histocompatibility complex-restricted cytotoxicity. The lytic activity seen in the 4-h assay with unseparated TILs appeared to be related to the presence of CD56+ populations. With one exception none of the purified CD4+ or CD8+ TILs expressed any significant levels of CD56, while the unseparated TILs contained varying numbers of CD3+CD56+ and CD3-CD56+ populations. Cell-sorting experiments verified that the CD56+ populations were responsible for most of the lytic activity in 4 h even though CD3+CD56- cells represented the predominant cell type. Although CD3+CD56- TILs were minimally lytic in 4 h, we show here that both CD3+CD4+ and CD3+CD8+ subsets displayed substantial cytotoxicity in long-term assays. In the 18-h 51Cr release assay 5 of 6 CD4+ and 2 of 3 CD8+ TILs were lytic for the autologous tumor. In two cases, restimulation with the autologous tumor induced augmented cytolytic activity of TIL subsets and in one case induced lytic activity in 4 h. The cytotoxic activity of TIL subsets was further examined using a 72-h assay in which TILs were cocultured with a confluent layer of tumor cells. The degree of cytotoxicity was quantitated by measuring the amount of crystal violet dye that was incorporated by tumor cells which remained after the incubation period. CD4+ and CD8+ TILs typically caused greater than a 50% reduction of tumor cells in 3 days and the level of reduction was increased when IL2 was added to the cultures. All the CD4+ and CD8+ subset preparations were cytotoxic in the 3-day assay even though some were not lytic for certain targets in the 18-h 51Cr release assay.(ABSTRACT TRUNCATED AT 400 WORDS)

The anatomic organization of the hippocampal formation in the cat was studied by means of (a) horseradish peroxidase histochemistry, (b) [3H]leucine radioautography, and (c) electrophysiological identification of antidromically activated single units. The data indicate that the CA1 field, prosubiculum, and adjacent subiculum are the source of origin of fibers terminating in the caudal septum. The subiculum and adjacent presubiculum are the only sources of hippocampal efferent fibers which project to the medial mammillary nucleus. The cells of the presubiculum and retrosplenial cortex give rise to the axons which project to the anterior thalamus. Efferent fibers project through the fornix and are topographically distributed to the mammillary bodies and septal area. Specifically, axons arising near the septal pole of the hippocampal formation project to the dorsal aspect of the medial mammillary nucleus or the dorsomedial part the lateral septal nucleus. Axons arising from cells situated progressively more proximal to the temporal pole of the hippocampal formation project to progressively more ventral levels of the medial mammillary nucleus or more lateral parts of the lateral septal nucleus. It was also noted that subicular fibers have slow conduction velocities and that evidence of possible axonal branching of fornix fibers was not obtained.

In a review of flight simulation performance experiments conducted at the U.S. Navy's Visual Technology Research simulator (VTRS), it was observed that individual difference variables accounted for a major portion of the total explained variance, in many cases more than the simulator equipment variables that were deliberately manipulated. This finding underscores the importance of individual differences in performance and training research in support of man-machine systems development and implementation. The identification of the substrates underlying individual differences will impact on equipment design considerations and training program requirements for military and industrial systems.

Suction ablations of the medial or lateral fornix were performed in order to transect selectively the medial corticohypothalamic tract (mcht) which originates in the anteroventral subiculum and travels in the lateral fornix terminating in the basal hypothalamus. The circadian rhythmicity of plasma adrenal corticosteroid levels was assessed in individual animals 1--2 weeks postoperatively. Ablation of the lateral fornix disrupted the periodicity of corticosteroid secretion which is normally synchronized with the light--dark cycle, whereas medial fornix ablation or neocortical ablation caused no such disruption. Group mean levels of plasma adrenal corticoids were higher in the lateral fornix-ablated animals than in the medial fornix-ablated, neocortically ablated, or intact control animals. These findings suggest that the anteroventral subiculum is important in the regulation of adrenal corticosteroid rhythmicity, and that it exerts an inhibitory influence upon corticosteroid release.

An experiment was performed to determine the origin of the projection from the hippocampus to the septal area in the subrimate mammalian nervous system. Lesions were made by aspiration or by radio frequency in 4 gerbils, 17 rats, 8 rabbits, and 7 cats. Survival times varied from 2–5 days. Tissues were stained principally with the Fink Heimer I method for identification of degenerating axons and their terminals. Following lesions destroying any one or more of the fields of the dorsal hippocampus of the gerbil, rat, rabbit, or cat, terminal degeneration was observed only in the medial septal area, olfactory tubercle, and adjacent portions of the diagonal band. In addition, lesions producing total destruction of all dorsal hippocampal fields also resulted in the presence of terminal degeneration restricted to the medial septal area. In contrast, superficial lesions of field CA1 of the ventral hippocampus produced terminal degeneration in the lateral septal area, nucleus accumbens, olfactory tubercle, and adjacent portions of the diagonal band. Similar findings were also observed following more widespread lesions of the ventral hippocampus which produced damage to other CA fields as well. Superficial lesions of the posterior crus of the hippocampus (i.e., a position midway between dorsal and ventral hippocampus) resulted in terminal degeneration localized to an intermediolateral region of the septum. Combined lesions of the dorsal hippocampus and fimbria produced widespread terminal degeneration in both the lateral and medial septum indicating that the axons contained within the fimbria arise only from the ventral hippocampus. Finally, lesions of the medial and lateral segments of the fornix of the cat produced terminal degeneration in the medial and lateral regions of the septum, respectively. These findings, collectively, indicate that the origin of the topographical projection to the medial and lateral septum are the dorsal and ventral hippocampus, respectively. This projection is unrelated to cytoarchitectonic fields within the hippocampus and is also invariant among the species considered in this study.

An experiment was performed to determine the role of the hippocampal formation in the regulation of quiet biting attach behavior elicited from electrical stimulation of the hypothalamus. The results showed clearly that stimulation of the dorsal hippocampus resulted in an increased latency to quiet biting attack and that ventral hippocampal stimulation resulted in a decreased latency to quiet biting attack. In addition, the results indicate that those sites in the ventral hippocampal formation from which facilitation of attack can be produced are linked to sensory mechanisms associated with trigeminal reflexes established during hypothalamic stimulation inasmuch as stimulation of these sites increase the lateral extent of the effective sensory field of the lipline. No effect was observed upon a motor component of the jaw-opening response--the latency to jaw-opening-during ventral hippocampal stimulation. In contrast, no effects were observed upon either sensory or motor components of the hypothalamically-elicited jaw-opening response as a result of stimulation of dorsal hippocampal sites. Deoxyglucose autoradiography revealed that the major effect of stimulation of modulatory sites in both the dorsal and ventral hippocampal formation was exerted upon the lateral septal nucleus. Thus, it is proposed that hippocampal modulation of hypothalamically-elicited quiet biting attack is mediated primarily through the lateral septal nucleus.

The history of research on visually-induced illusory self motion, or vection, has demonstrated that in many instances observers have experienced disturbances similar to those of motion sickness. Visual displays in flight simulators may also produce the experience of vection, and illusions of self motion are likely to become more common with the increased use of wide field-of-view presentations of realistic imagery. Many of the disturbances observed in laboratory studies of vection have also been found in simulators, and are likely to become more common. This paper presents a background to the study of visual-vestibular disturbances associated with illusory self motion in flight simulators, and an overview of current experimental efforts aimed at identifying the causal factors.

An experiment was performed to determine the role of the lateral aspect of the prefrontal cortex upon quiet biting attack behavior elicited from the hypothalamus in the cat. The results of this experiment indicate that stimulation of 19 of 28 electrode sites sampled in the lateral prefrontal cortex produced a statistically significant inhibition of attack behavior elicited from the hypothalamus of the ipsilateral side. Stimulation of sites in the prefrontal cortex on the side contralateral to the hypothalamus from which attack was elicited had no effect upon this response. No systematic effect of prefrontal stimulation upon flight behavior was observed. Anatomical studies suggest that the lateral prefrontal cortex may inhibit attack behavior by modulating neurons in either the mediodorsal thalamic nucleus or ventral tegmental area.

The present review summarizes our research findings concerning the role of the limbic system in hypothalamically-elicited aggression in the cat. Utilizing a dual-stimulation procedure, our results indicate that much of the limbic system suppresses quiet biting attack behavior. The most potent inhibitory effects were obtained from the basomedial amygdala and the prefrontal cortex. Other structures displaying suppression of attack following electrical stimulation include the dorsal hippocampus, pyriform cortex, lateral septal nucleus, lateral aspect of substantia innominata, and anterior cingulate gyrus. Sites producing facilitation of attack include the ventral hippocampus, far lateral aspect of the lateral septal nucleus, medial aspect of the substantia innominata, and lateral amygdaloid nucleus. Anatomical studies suggest that the medial forebrain bundle and stria terminalis are utilized by limbic structures to provide direct modulation of the hypothalamus while the substantia innominata, mediodorsal thalamic nucleus and bed nucleus of the stria terminalis contain important interneurons in the control of quiet biting attack. Further studies indicate that the amygdala, ventral hippocampus, and substantia innominata may control aggressive behavior by modulating the trigeminal sensory components of the attack response.

The purpose of this study was to determine the effect of electrical stimulation of the lateral hypothalamus and preoptic area on second- and higher-order neurons in the ventral tegmental area of the mesencephalon. Single-unit responses were recorded by tungsten microelectrodes in anesthetized cats. Lateral hypothalamic stimulation caused short- and long-latency excitation as well as antidromic activation of ventral tegmental area neurons. However, half of the responsive neurons exhibited a suppression of firing, or inhibition, following stimulation. The short latency of onset of the suppression obtained in some of these neurons suggests the possibility that, in addition to a descending excitatory hypothalamic outflow, descending monosynaptic inhibitory pathways to the ventral tegmental area are also present.

The present study investigated the response characteristics of individual neurons in the amygdala following stimulation of the substantia innominata (SI), and compared these responses with those elicited by stimulation of insular and temporal polar cortices and the lateral olfactory tract (LOT). Recordings were made from single units within the medial, central, basal, and lateral amygdaloid nuclei of anesthetized, male cats. Stimulating electrodes were located in the SI, LOT, and sylvian cortex (SG). Unit responses were classified as either excitation or inhibition. Excitatory responses were further divided into fixed latency excitation (FLE) and variable latency excitation (VLE) based on the variability of the onset latency of the response. The majority of responses to SI stimulation were of the FLE type, implying a direct orthodromic, monosynaptic activation of amygdaloid units. Proportionally more FLE responses were recorded laterally, especially in the magnocellular basal nucleus, compared to VLE responses which were common in the medial and central nuclei. SI stimulation consistently affected the activity of many more units than did SG or LOT stimulation. The onset latencies of the population of cells exhibiting excitatory responses elicited by SI stimulation were distributed bimodally, and this may reflect a dual projection pathway of amygdaloid afferents from this basal forebrain region. This correlates with anatomical descriptions indicating that SI projections to amygdala pass via the ventral amygdalofugal pathway as well as in the stria terminalis. Excitatory onset latencies of responses to SI stimulation were the shortest in the lateral and magnocellular basal nuclei and the longest in the parvocellular basal nucleus. Amygdaloid units exhibited convergent input from the stimulus sites. A clear topographical distribution of units was not demonstrated. The data suggests that units receiving a convergent input were rarely driven monosynaptically by more than one stimulus site. The basal nucleus contained the smallest fraction of units exhibiting a convergent input. A small population of antidromic responses was recorded and indicates that within the system studied the caudal aspect of the basal nucleus is a major source of amygdaloid efferents. Antidromically driven units did not exhibit transynaptic responses following stimulation of any of the test sites.

Extracellular unit recordings were obtained from the nucleus medialis dorsalis (MD) and adjacent thalamic nuclei and from the hypothalamus of anesthetized cats. Electrical stimulation of the prefrontal cortex produces suppression of unit activity and rebound excitation in MD. In addition antidromic and short latency excitation was found which was followed by prolonged suppression of firing. This suppression was also followed by a strong postinihibitory activation of unit firing which was, in some cases, again followed by a second phase of inhibition. Amygdala stimulation produced similar results except that antidromic responses were found only in the intralaminar nuclei, and short-latency transynaptic excitation occurred somewhat later. The results are in consonance with the hypothesis that the same interneuronal mechanism is engaged by both afferent sources to MD. In the hypothalamus, fewer units responded to cortical and amygdalar stimulation and alternating sequences of excitation-inhibition-excitation were not found.

Summary An experiment was performed to determine the projections of the anterior, central, and posterior regions of hippocampus to the septum in the squirrel monkey. Lesions were placed in each of these regions of hippocampus in 18 animals. Survival times varied from 5 to 7 days. Tissues were stained principally by the Fink-Heimer I method for identification of degenerating axons and their terminals. Following lesions which destroyed one or more fields of the anterior third of hippocampus degenerating axons were traced through the fimbria and fornix to the lateral septal area where dense quantities of terminal degeneration were observed. Smaller quantities of terminal degeneration were noted in the nucleus accumbens as well. After lesions of the middle third of hippocampus terminal degeneration was observed in an intermediolateral position within the septum. Following lesions of the posterior third of hippocampus degenerating terminals were observed in the area of the medial septum. All regions of hippocampus send fibers to the nucleus of the diagonal band and to the olfactory tubercle. These findings indicate that in the primate the projection to the septum from the hippocampus is topographically organized along its longitudinal axis in a manner that links the anterior hippocampus to the lateral septum and the posterior hippocampus to the medial septum.

The purpose of this study was to describe the hypothalamic pathways which mediate affective defense in the cat utilizing the methods of [14C]2-deoxyglucose (2-DG) and [3H]leucine radioautography in concert with the technique of electrical brain stimulation. The feline affective defense response, characterized by pupillary dilatation, piloerection, ear retraction, hissing, growling and striking with the forepaws, was elicited consistently by stimulation of sites within the ventromedial hypothalamus and anterior aspect of the medial hypothalamus. In one series of experiments, 2-DG autoradiography was employed to describe the brain regions activated following stimulation of sites in the region of the ventromedial hypothalamus from which affective defense had been elicited. Ventromedial hypothalamic stimulation produced activation primarily in forebrain regions situated rostral to the level of the stimulating electrode. These structures included principally the anteromedial hypothalamus and medial preoptic area, as well as the bed nuclei of the stria terminalis and anterior commissure, diagonal band and lateral septal area. The caudal extent of activation included only the dorsal and perifornical hypothalamus at the level of the stimulation site. In a second series of experiments, affective defense sites in the anteromedial hypothalamus were stimulated and the regional distribution of 2-DG label was identified. In contrast to the results obtained from ventromedial hypothalamic stimulation, these experiments revealed a marked descending distribution of label within the posterior hypothalamus, midbrain central gray and ventral tegmental area. Results obtained from studies in which tritiated amino acids were injected into affective defense sites in both the ventromedial nucleus and anteromedial hypothalamus confirmed the general findings observed with 2-DG autoradiography. From these observations, we have concluded that the organization of the pathway mediating affective defense behavior from the ventromedial hypothalamus to the midbrain involves an initial synapse within the region of the anteromedial hypothalamus and a second synapse in the midbrain central gray substance. The significance of the anteromedial hypothalamus for the expression of affective defense behavior was considered in the Discussion.

Phosphorylation of mouse epidermal proteins by endogenous protein kinases and production of arachidonic acid are processes stimulated by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. In mouse epidermal homogenates, each process, as well as production of diacylglycerol (the physiologic activator of protein kinase C), was inhibited by bromophenacyl bromide at concentrations equivalent to those that inhibit tumor promotion. These results lend support to the hypothesis that tumor promotion in mouse skin may be mediated by activation of protein kinase C.

Experiments were performed in cats to determine the pathway from the thalamic mediodorsal nucleus to the hypothalamus. In the first stage, lesions were placed in the mediodorsal nucleus and degenerating fibers were traced to the posterior half of the midline thalamus but not to the hypothalamus. In the second stage, lesions were placed within the posterior half of the midline thalamus and fibers were traced to the anterior half of midline thalamus, but not to any part of the hypothalamus. In the third stage, lesions were placed in the anterior half of midline thalamus and terminal degeneration was observed in the anterior portion of the perifornical lateral hypothalamus after short survival times were employed. These findings suggest the existence of a fine-caliber fiber system from the anterior midline thalamus to the hypothalamus. The results indicate a multisynaptic circuit from the mediodorsal nucleus of the thalamus to the hypothalamus which can be summarized as follows: mediodorsal nucleus → posterior midline thalamus → anterior midline thalamus → anterior lateral hypothalamus.