Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, positron emission tomography (PET) has been the only technology for the quantitative imaging of the changes of regional cerebral glucose (rCMRGl) or oxygen metabolism and blood flow (rCBF) associated with psychophysical stimulation and with the performance of mental tasks. So far, the majority of studies performed in healthy subjects demonstrated activation patterns involving not only certain limbic structures, most of all hippocampus, amygdala, parahippocampus, and cingulate, but also temporal, parietal, and occipital association cortex, depending on the applied paradigm. Indeed, the closest correlation between regional metabolism and memory test scores was found in mesiotemporal structures during the performance of memory tasks. Metabolic or CBF studies also seem to indicate that memorizing strategies may differ among individuals. PET was repeatedly used to investigate metabolic and/or blood flow abnormalities in patients with various amnestic syndromes. In cases with uni- or bilateral lesions of mesiotemporal structures, caused by surgery, herpes simplex encephalitis, or permanent ischemic, anoxic, or toxic damage, disturbances of metabolism and blood flow typically extended far beyond the morphological defects detected by computed tomography or magnetic resonance. In acute transient global amnesia, CBF and metabolism were decreased bilaterally in the mesiotemporal lobes, where hypometabolism persisted for some time, while higher values were observed in thalamus and some cortical areas. Diencephalic lesions causing Korsakoff's syndrome were associated with decreased rCMRGl in the hippocampal formation, upper brainstem, cingulate, and thalamus. Discrete thalamic infarcts caused amnesia and metabolic depression in the morphologically intact ipsilateral thalamus and in various projection areas of the infarcted nuclei. In ischemic forebrain lesions, amnestic deficits could be related to involvement of the anterior cingulate and of basal cholinergic nuclei. A large number of pathologies are diffusely spread out in the brain and affect partially or predominantly structures in memory processing. This holds true especially in the various dementias where memory disturbances are a consistent and often leading feature. Notably, Alzheimer's disease can be distinguished from other dementias by its characteristic pattern of metabolic dysfunction, with the most prominent changes occurring in parietotemporal and frontal association cortex whose residual metabolism is related to the severity of the disease. Therefore, activation studies using paradigms involving memory functions enhance that typical pattern. Only in the activated state is metabolism of mesiotemporal structures significantly correlated with the performance in memory tests. Other dementias also affect some of the distributed memory networks, with Huntington's disease suggesting a role of the striatum in memory processing.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:PET correlates of normal and impaired memory functions. 156 50

Work done in our laboratories, using a murine model, indicates that suppression of host immune responses might be due to secretion of soluble factors by tumor cells. The H238 cells (BALB/c embryonic fibroblasts transformed by UV-inactivated herpes simplex virus Type 2) exhibit progressive tumor growth with subsequent decrease in lymphoproliferation. To further study the suppressive effects of a tumor, H238 conditioned medium (CM) was tested for its ability to block murine and human mitogenic and allogeneic lymphocyte responses. PHA, Con A and LPS were used as mitogens. Lymphoproliferation, in the presence of increasing amounts of H238 CM, resulted in a greater degree of suppression of [3H]thymidine ([3H]Tdr) uptake, in both human and mouse systems. The kinetics of proliferation in the presence of concentrated H238 CM (cCM) showed that depression was evident regardless of the time of cCM addition, thereby affecting it at any stage of the cell cycle. Treatment of H238 cCM using acid (pH 2.3), base (pH 9.6), trypsin (100 micrograms/ml), heat (56 degrees C, 100 degrees C) and freeze-thawing, restored PHA-stimulated lymphoproliferation. Dialysis of H238 cCM showed that the molecular weight of the suppressor lies between 15 and 25 kDa. Northern blot analysis demonstrated the presence of a TGF-beta transcript in H238 cells. Neutralization of the H238 cCM with monoclonal antibody to TGF-beta resulted in complete abrogation of suppressive activity in spleen cell lymphoblastogenesis. These results suggest that TGF-beta appears to be the main inhibitor of immune responses found in this HSV-2-induced murine tumor cell line. Such tumor-induced modulations may contribute to the outcome of immunotherapy in the tumor-bearing host.
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PMID:Suppression of immune responses by herpes virus type 2-transformed murine tumor cells. 166 30

The current results provide direct evidence for a role of tissue macrophages (M phi) in natural immunity and support the use of immunomodulators to enhance antiviral resistance in immunocompromised individuals. In this study, macrophages (M phi) in the spleen and liver were eliminated by intravenous (i.v.) injection of the drug dichloromethylene diphosphonate (DMDP) encapsulated in liposomes. The effect of this depletion system on peritoneal M phi, peripheral blood leukocytes, splenic natural killer (NK) activity, and natural and immunomodulator-induced host resistance was then assessed. Barrier-maintained CD-1 female mice were inoculated i.v. either with DMDP liposomes, free liposomes (containing no DMDP), or saline on day -2 or on days -3 and -1 before cell population analysis or infection. Single or double treatment with DMDP liposomes had no effect on peritoneal M phi as indicated by no changes in total number, differential counts, or ectoenzyme patterns. Double treatment with DMDP liposomes caused a marked leukocytosis in blood, primarily of lymphocytes and polymorphonuclear leukocytes (PMN), and a transient depression of spontaneous and interferon-inducible splenic NK activity. The effects on host resistance to i.v. infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) indicated that i.v. treatment with DMDP liposomes significantly reduced natural resistance to these microorganisms as evidenced by increased mortality and decreased median survival time. When DMDP liposomes-treated mice were given the immunomodulator maleic anhydride divinyl ether copolymer (MVE-2) intraperitoneally the day before infection with HSV-2, the immunosuppressive effect of DMDP liposomes treatment was significantly reversed.
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PMID:Selective depletion of liver and splenic macrophages using liposomes encapsulating the drug dichloromethylene diphosphonate: effects on antimicrobial resistance. 182 90

Plasma inhibitory factors, high levels of sex hormones, and depression of cell-mediated immunity may interfere with the natural host resistance to viral infections during pregnancy. It is apparent that hormonal, immunologic, and vascular changes in pregnancy may account for increased replication of herpes and for enhanced growth of condylomatous lesions. The challenge is to develop a rational plan of management for pregnant patients with herpes simplex or human papilloma virus infection. There has been a reevaluation of previous recommendations for the management of herpes in pregnancy. Although the consequences of neonatal infection are severe or fatal, the value of routine weekly screening is questionable. This regimen is a poor predictor of neonatal exposure to herpes since only one fourth of women shedding virus at the time of delivery can be identified by routine cultures. The mode of delivery should therefore be based on the presence or absence of lesions at the time of confinement. Cesarean section should be reserved for patients with lesions or with prodromal symptoms of recurrent disease at the time of delivery. Patients with ruptured membranes and active genital lesions should also be delivered by cesarean section. The spectrum of HPV-related diseases in pregnancy is poorly understood. Many questions remain unanswered. It may not be practical to treat very large or extensive genital warts during pregnancy. A cesarean section may be the best choice in these cases. It may be premature to recommend cesarean section for delivery of all pregnant women with symptomatic genital HPV infection. More data are needed. We recommend laser ablation of condylomatous lesions when discovered during pregnancy. Laser vaporization is associated with minimal morbidity when used by experienced surgeons. Trichloroacetic acid is excellent for minimal disease or for treatment of recurrences in pregnancy. Since the immune system seems to play an important role in control of viral disease, we advise pregnant patients to adopt a lifestyle which promotes health. We advise a balanced diet, an appropriate exercise program, and an environment free of unnecessary stress. We suggest avoidance of cigarettes, drugs, and alcohol.
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PMID:Herpes simplex and human papillomavirus genital infections: controversy over obstetric management. 196 24

Herpes type infections in AIDS patients tend to be more severe, generalized and have a torpid evolution. We present here two cases of intravenous drug addicts with a clinical picture of ulcerative lesions with a scar in the perioral and ungual regions with an evolution of several months an which were diagnosed of Herpes Simplex by a histopathological study. They were treated with intravenous Acyclovir achieving a complete remission; one patient developed a pneumocystis carinii pneumonia a month later. We want to highlight the importance of this case as a clinical sign of profound cellular immunity depression as well as the risk of developing more severe conditions.
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PMID:[Herpes simplex infections in patients with AIDS]. 237 75

The activity of red-cell C3b receptor and the level of circulating immuno-complex in 35 cases of herpes simplex stromal keratitis were determined, with the results that during the stage of acute attack, the former was significantly lowered, while the level of the latter became markedly higher than that of the controls, and after treatment, the indicators returned to normal values. There was a negative correlation between the red-cell C3b receptor activity and the circulating immuno-complex in serum, indicating that the immuno-function of red-cells in patients with herpes simplex stromal keratitis was impaired and the depression of red-cell C3b receptor activity was one of the reasons for the elevated concentration of circulating immuno-complex in serum.
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PMID:[Activity of the red-cell C3b receptor and the circulating immuno-complex in patients of herpes simplex keratitis]. 253 77

Sixty-five patients with recrudescent orofacial herpes simplex virus (HSV) infections all had circulating HSV-specific antibody measured by ELISA and cell-mediated immunity (CMI) to HSV by in vitro lymphoproliferation. Thirteen control subjects with no history of HSV were negative for both tests. Thirty-three patients, repeatedly investigated during 6 to 38 months, had between 1 and 8 recrudescences each. Lymphoproliferative responses to HSV were low during recrudescence, rose to a peak a few weeks later and then declined to a positive background level. However, ELISA titres and lymphoproliferative responses to concanavalin A were high throughout, and peripheral blood mononuclear cell (PBMC) subset numbers measured by fluorescent flow cytometry remained within normal limits. During HSV lesions, depressed lymphoproliferation to HSV was abrogated by removal of CD8+ T cells from PBMC either by using a panning technique (nine patients) or by cell sorting (three patients). Reconstitution of the CD8-depleted population suppressed the lymphoproliferative response to HSV. Depletion of CD8+ T cells did not affect lymphoproliferation to HSV outwith recrudescence (four patients), nor lymphoproliferative responses to another antigen (PPD; five patients) during recrudescence. Thus, reduced lymphoproliferation to HSV during recrudescence may be due to HSV-specific CD8+ suppressor T lymphocyte function, rather than lack of HSV-responsive lymphocytes. This may result in depression of normal CMI responses to the virus during an asymptomatic recurrence allowing recrudescent lesions to develop.
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PMID:Variation in lymphoproliferative responses during recrudescent orofacial herpes simplex virus infections. 255 8

The replication of type 1 and type 2 strains of herpes simplex virus (HSV) was inhibited greater than 99.9% by low concentrations (0.1-0.2 microM) of anthracycline compounds. The degree of viral inhibition was dependent upon the host cell. N,N-dimethyl daunomycin (NDMD), a non-mutagenic compound, was more potent as an inhibitor of HSV synthesis than either daunomycin (DM) or adriamycin (AD). The depression of viral yield by DM or AD was attributable, in part, to a temperature-dependent direct effect on infectious virions. Tritium-labeled DM bound tightly to HSV particles. NDMD did not directly inactivate virions in spite of superior potency in reducing viral yields. All three anthracyclines could be added late in the infectious cycle (6-8 h p.i.) and retain effectiveness. Cesium chloride density gradient analysis verified that viral DNA synthesis was blocked by addition of all three anthracyclines early in the infectious cycle. The inhibition of HSV replication was not a simple consequence of the suppression of host DNA synthesis since treatment of cells with compounds for 24 h before infection did not reduce virus yields even though host DNA synthesis was inhibited by 90%. Further, the kinetics of inhibition of cellular DNA synthesis by anthracyclines was similar in HFF or Vero cells but the degree of inhibition of virus replication was markedly different. The data suggest that anthracyclines with substitutions on the sugar moiety may be useful anti-herpes agents.
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PMID:Inhibition of herpes simplex virus replication by anthracycline compounds. 283 Aug 45

During infection with herpes simplex virus type 1 (HSV-1) the activity of tyrosine hydroxylase (TH) in PC12 pheochromocytoma cells was initially depressed reaching a nadir at 6 hours post-inoculation, but recovered rapidly with a return to baseline activity by 8 to 9 hours post-inoculation. Subsequently, TH activity again fell with a second more variable rise in activity occurring at 24 hours post-inoculation. Studies with metabolic inhibitors and 2 temperature-sensitive viral mutants indicated that these alterations of TH activity were dissociated from morphological cytopathology and likely required expression of "late" viral gene products. Immunotitration using anti-TH antibody suggested that early depression of TH activity resulted principally from loss of enzyme protein rather than simple enzyme inactivation, and that reconstitution of activity at 9 hours was related to augmented enzyme synthesis. These observations illustrate the complexity of perturbed cellular metabolism during HSV-1 infection and suggest involvement of two unexpected processes: alteration of a specialized cell function as a result of viral genes expressed late in the replicative cycle, and augmented synthesis of a cell-coded gene product during the course of infection.
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PMID:Alteration of tyrosine hydroxylase activity in PC12 cells infected with herpes simplex virus type 1. 285 60

The immunosuppressive effects of three herpesviruses--cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simplex virus (HSV)--were assessed in 29 renal transplant recipients treated with cyclosporine and prednisone. The ratios of Leu 3-positive ("helper-inducer") to Leu 2-positive ("suppressor-cytotoxic") T lymphocytes in peripheral blood were only moderately and transiently decreased during primary CMV infection, with or without concurrent reactivated EBV and HSV infections. This effect was due to an increase in absolute numbers of Leu 2-phenotypic and decrease in Leu 3-phenotypic T cells and was associated with symptomatic viral illness. Reactivated CMV infection alone or together with reactivated EBV and HSV infections resulted in less significant alterations in T-cell subsets than did primary CMV infection. Lymphocyte blastogenesis was not significantly altered during the herpesvirus infections. The data suggest that cyclosporine treatment inhibits the activation of suppressor cells and depression of cellular immune function that have been associated with herpesvirus infections in renal transplant recipients undergoing conventional immunotherapy.
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PMID:Effect of herpesvirus infections on T-lymphocyte subpopulations and blastogenic responses in renal transplant recipients receiving cyclosporine. 300 96


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