Role of p38 MAPK inhibitor in conditioned fear

p38 mitogen activated protein kinase (p38) is a kinase that has been implicated in cellular plasticity, stress, and psychiatric disorders and recently in the process of DNA repair. Recently, we have shown that p38 is responsible for inhibiting Glycogen Synthase Kinase 3β (GSK3β), which has also been shown to be involved in the same processes and recently in the process of DNA repair. We have also shown that GSK3β is regulated by stress and that its inhibition produces exaggerated conditioned fear. The goal of this study is to examine whether inhibiting p38 will result in a similar exaggeration of conditioned fear. To this end, mice were injected systemically with the potent and selective inhibitor of p38, SB203580 or vehicle prior to tone and foots­hock fear conditioning and tested for freezing to the tone one day later. Mice injected with SB203580 showed greater tone freezing than mice injected with vehicle. In contrast to tone freezing, SB203580 injections did not affect freezing to the context. Injections of SB203580 prior to 24 hours after fear conditioning, but before fear testing, also did not affect freezing. These data suggest that p38 plays a role in regulating the strength of conditioned fear. The fact that p38 regulates GSK3β and that inhibition of GSK3β also produces exaggerated conditioned fear raises the possibility that a p38 to GSK3β pathway may be regulating the strength of conditioned fear

Pyelonephritis

The purpose of this paper is to review current thinking about pyelonephritis. Pyelonephritis may be defined as a bacterial infection of the kidney which affects the parenchyma, the pelvis, and the calyces. It occurs in two forms, acute and chronic

The Management of End-Stage Renal Disease (ESRD)

End-stage renal disease (ESRD) may be defined as a state of renal insufficiency of such severity that the affected individual is unable to carry out his usual activities because of symptoms usually attributed to the uremic syndrome. This state has been reached, or is imminent, when the serum creatinine concentration rises above 10 mg/100 ml and/or the creatinine clearance falls below 5 to 10 ml/min and reversible causes of renal failure such as obstructive uropathy, bilateral renal vascular disease, severe accelerated hypertension, hypercalcemic nephropathy, uric acid nephropathy, and certain immunologic diseases such as Wegener granulomatosis have been excluded. Prospective analysis of a population of patients meeting these biochemical criteria has clearly shown that at least 80% will require dialysis within 1500 days and 40% will require this method of treatment within 60 day to sustain life. Thus when ESRD is reached, weighty decisions concerning the patient’s care must be made. It is the purpose of this paper to review the management of ESRD and to point out some of the problems which may complicate the several therapeutic modalities

Immunology and Disease of the Kidney

The emphasis of this paper is the review of several aspects of renal disease which have immunologic overtones and clinical relevance. The pathogenesis of several subtypes of glomerulonephritis will be discussed, the immunologic implications of amyloidosis will be noted, and the relation between immune mechanisms and tubulointerstitial disease will be mentioned. The discussion will then be completed by an analysis of the prognosis of the aforementioned renal disease, and by an attempt to place contemporary therapeutic modalities in a proper perspective

Spin Modulation in Semiconductor Lasers

We provide an analytic study of the dynamics of semiconductor lasers with injection (pump) of spin-polarized electrons, previously considered in the steady-state regime. Using complementary approaches of quasi-static and small signal analyses, we elucidate how the spin modulation in semiconductor lasers can improve performance, as compared to the conventional (spin-unpolarized) counterparts. We reveal that the spin-polarized injection can lead to an enhanced bandwidth and desirable switching properties of spin-lasers.Comment: 4 pages, 3 figure

Extinction of Fear-potentiated Startle: Blockade by Infusion of an NMDA Antagonist into the Amygdala

Data derived from in vitro preparations indicate that NMDA receptors play a critical role in synaptic plasticity in the CNS. More recently, in vivo pharmacological manipulations have suggested that an NMDA-dependent process may be involved in specific forms of behavioral plasticity. All of the work thus far has focused on the possible role of NMDA receptors in the acquisition of responses. However, there are many examples in the behavioral literature of learning-induced changes that involve the reduction or elimination of a previously acquired response. Experimental extinction is a primary example of the elimination of a learned response. Experimental extinction is well described in the behavioral literature, but has not received the same attention in the neurobiological literature. As a result, the neural mechanisms that underlie this important form of learning are not at all understood. In the present experiments, the fear-potentiated startle paradigm was employed to begin to investigate neural mechanisms of extinction. The results show that infusion of the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure known to be important for fear conditioning, dose-dependently blocked extinction of conditioned fear. Control experiments showed that the blockade of extinction was neither the result of the permanent disruption of amygdaloid function nor the result of decreased sensitivity of the animals to the conditioned stimulus. Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site, did not block extinction. Finally, intra-amygdala infusion of a selected dose of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block extinction of conditioned fear. These results, together with a previous report from our laboratory (Miserendino et al., 1990), demonstrate the importance of the amygdala in the elaboration of conditioned fear and suggest that an NMDA-dependent process might underlie the extinction of conditioned fear

Clinical Aspects of Renal Tubular Disorders

I have tried to briefly outline aspects of the presently recognized disorders of tubular function that are of clinical importance. I would like to stress again that, although such disorders constitute a minute portion of the total health problem in this country, they are of great importance as experiments of nature, study of which is opening the way for a clearer understanding of fundamental transport mechanisms in the renal tubule. Additionally, for those individuals afflicted with any of the disorders I have mentioned, the availability of relief is of paramount importance. Such relief can be obtained in some cases by correct diagnosis and proper application of physiologically oriented therapy

Glomerulonephritis

In this paper the histologic picture of the most common disorders usually classified under the heading of glomerulonephritis will be reviewed, and the subject of angiitis will be briefly addressed. A special effort will be made to relate renal biopsy findings to the immunologically mediated pathogenetic process which is thought to be operative in each case. Where it seems appropriate, a few comments will also be made on clinical and pathological correlations. The specific entities to be covered include: diffuse proliferative glomerulonephritis; focal proliferative glomerulonephritis; membranous glomerulonephritis; antibasement membrane antibody disease; rapidly progressive glomerulonephritis (crescentic disease); membranoproliferative glomerulonephritis; lipoid nephrosis (nil disease); focal; segmental; and global sclerosis; polyarteritis nodosa; hypersensitivity angiitis; and Wegener granulomatosis. Few comments will be made about therapy because that subject is covered elsewhere in this issue. The review will be concluded by a discussion of the prognostic value of information gleaned from careful biopsy evaluation

Canadian Niagara Power League Meeting (1897)

Remarks of Mr. William B. Rankine, secretary of the Canadian Niagara Power Company

Lesions of the Perirhinal Cortex but Not of the Frontal, Medial Prefrontal, Visual, or Insular Cortex Block Fear-Potentiated Startle Using a Visual Conditioned Stimulus

The present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and l-2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3-4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory