Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum

The relationship between the postnatal development of dopaminergic (DAergic) nerve endings and the maturation of D1 DA receptors in the rat striatum was analyzed by measuring the content of DA and dihydroxyphenylacetic acid (DOPAC), two biochemical markers of DAergic nerve terminal proliferation, and the ontogenetic changes in [3H]SCH 23390 binding sites. DA-stimulated adenylate cyclase (AC) activity was also measured in order to characterize the coupling of [3H]SCH 23390 binding sites to the responses mediated by the activation of D1 DA receptors. Striatal levels of DA and DOPAC, as well as the density and affinity of [3H]SCH 23390 binding sites and DA-stimulated AC activity were also measured in senescent rats. The striatal content of DA increased slowly after birth, reaching adult levels by postnatal day 60 and remaining constant through adulthood and senescence (up to 20 months of age). The density of [3H]SCH 23390 binding sites increased 14-fold from birth to postnatal day 35, when a peak value was reached, whereas a significant decrease was observed in the striatum of aged rats. In contrast, the affinity of D1 DA receptors for [3H]SCH 23390 remained unchanged from birth through senescence. The stimulation of cyclic AMP formation induced by 100 microM DA increased 4-fold from birth to postnatal day 14, when the maximal responsiveness to DA was observed and then returned to adult levels. No significant alterations were observed in the Km values during development, whereas the stimulatory effect of 100 microM DA on AC activity was significantly decreased in senescent rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blue Hue in the Dermoscopy Setting: Homogeneous Blue Pigmentation, Gray-Blue Area, and/or Whitish Blue Veil?

In dermoscopy, the correct recognition of the single parameters is fundamental to achieve great diagnostic accuracy, but the scarce morphologic expression of a parameter may lead to diagnostic errors. We report the case of a 27-year-old white man presenting a pigmented lesion of the back, which was present since puberty. Clinical examination revealed on the back the presence of a flat, gray-blue lesion and at the periphery a small dark-brown papule. An assessment of the lesion by means of dermoscopy was performed. The purpose of this report was to analyze the Blue Hue in dermoscopy with its histopathologic correlates, starting with the discussion of a clinical case.     

Strain differences in mouse cellular responses to Mycobacterium lepraemurium and BCG subcutaneous infections. I. Analysis of cell surface phenotype in local granulomas.

C57BL/6, BALB/c and CBA mice were subcutaneously infected with either Mycobacterium lepraemurium (MLM) or BCG, and studied for bacillary growth, granuloma size of infected footpads and draining lymph nodes (DLN), and DLN cell surface phenotype. Whereas, BCG-infected mice controlled the infection and developed early and large granulomas, MLM-infected mice exhibited major strain variations in their resistance to the infection, as well as in the granuloma size and kinetics. C57BL/6 mice, highly resistant, displayed early and regressive granulomas; BALB/c mice showed lower resistance and early granulomas that grew continuously; CBA mice, highly susceptible, developed late, soft, phagocyte-rich granulomas. Important strain differences in lymph node lymphocyte subset distribution could be observed prior to any infection: C57BL/6 mice displayed higher B cell percentages than both of the other strains and BALB/c mice showed the highest CD4/CD8 ratios, followed by CBA and C57BL/6 mice. BCG and MLM infections both induced similar changes of these parameters in all three strains: that is a decrease of the B cell percentage and a decrease of the CD4/CD8 ratio, and the strain differences observed in uninfected mice persisted. On the other hand, DLN cells stimulated by the infecting bacillus and interleukin 2 also displayed an increase of the CD8 T cell percentage as compared with normal lymph node cells, but this phenomenon was much less pronounced in BALB/c mice, whether infected by MLM or BCG, and in MLM-infected CBA mice, than in BCG- or MLM-infected C57BL/6 (B6) mice. Thus the ability of C57BL/6 mice to generate an early and persistent CD8 T cell response to mycobacteria may contribute to their resistance to MLM.     

Child with oral,facial, digital,and skeletal anomalies and psychomotor delay: A new ofds form?

We report on a male infant with oral, facial, digital, and skeletal anomalies in association with severe psychomotor delay. This may represent a new oral-facial-digital syndrome. © 1994 Wiley-Liss, Inc.     

Immunology of HIV infection

The goal of finding an effective vaccine against the human immunodeficiency virus (HIV) is hampered by our uncertainty of the mechanism(s) responsible for the pathogenesis as well as the lack of knowledge of protective mechanisms. The effects of HIV on the immune system are myriad and thus the truly significant manifestations of the pathology are difficult to dissociate from those more peripheral. In this article we will initially characterize the natural history of HIV infection which shows a chronic and perhaps inexorable course. The second part will deal with the immune response mounted against this assault and the final section is a discussion of the possible unfavorable consequences of the immune response that humans muster against this agent.     

Causal pathways for CCR5 genotype and HIV progression

A homozygous 32-bp deletion in the gene encoding CCR5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1, and heterozygosity for the deletion is associated with delayed disease progression in persons infected with HIV-1. We investigated the effect of CCR5 heterozygosity on disease progression as measured by both CD4+ T-cell count decline and the occurrence of clinical AIDS symptoms. Using a unified statistical model for CD4 count progression and AIDS development, we examined whether the effect of CCR5 heterozygosity on clinical AIDS is direct or indirect through its effect on CD4 counts. Based on data from the Multicenter AIDS Cohort Study, we noted a protective effect of CCR5 heterozygosity on both CD4 cell count progression and on AIDS occurrence. Furthermore, we found that this protective effect on the occurrence of AIDS was completely mediated through an effect on the CD4 marker. Additional adjustment for the effect of an initial viral load measurement indicate that CCR5 heterozygosity did not have predictive value for either CD4 progression or the development of AIDS beyond its association with early viral load.     

Increase and plateau of CD4 T-cell counts in the 3(1/2) years after initiation of potent antiretroviral therapy

We evaluated CD4 cell counts over a 3(1/2) year period following the initiation of potent antiretroviral therapy (ART) in the Multicenter AIDS Cohort Study. The study population included 314 HIV-infected gay men who provided CD4 cell counts for at least 2 years after the initiation of potent ART. Trends in CD4 cell counts and plasma HIV-RNA were analyzed by regression methods that incorporated the statistical dependencies of outcomes measured over time within individuals. Regardless of CD4 cell count at initiation of potent ART, CD4 cell counts increased significantly (p <.05) in the first 2 years after initiation. However, between 2 and 3(1/2) years after initiation, these counts neither increased nor decreased. The pattern of the proportion with plasma HIV-RNA <400 copies/ml was similar to CD4 cell count (i.e., increased significantly after initiation and plateau in the subsequent 1(1/2) years). The single most important predictor of the steady state CD4 cell count that was maintained between 2 and 3(1/2) years after initiation was the change in plasma HIV-RNA in the first year after initiation of potent ART.     

The abstinence syndrome in diazepam-dependent cats is precipitated by Ro 15-1788 and Ro 15-4513 but not by the benzodiazepine receptor antagonist ZK 93426

Diazepam-dependent cats were challenged with different benzodiazepine recognition site ligands 24 h after the last dose of chronic treatment with diazepam (7 mg/kg, i.p. at 08.00 and 20.00 h, for 21 consecutive days). The benzodiazepine derivatives Ro 15-4513 (a partial inverse agonist) and Ro 15-1788 (a pure antagonist), precipitated an abstinence syndrome within minutes after i.p. administration. Abstinence signs included tremors, increased muscle tone, irritability, fear, pupillary dilation and vocalizations. On the contrary, the beta-carboline derivatives ZK 93426 (an antagonist) and FG 7142 (a partial inverse agonist) failed to precipitate abstinence signs in diazepam-dependent cats when given at doses that prevented the acute effects of diazepam. Our results demonstrate that the ability to induce withdrawal signs in diazepam-dependent cats strongly depends on the benzodiazepine structure of the challenge drug since beta-carboline antagonist and partial inverse agonists lack this property.