Plasma cell infiltration of the conjunctiva associated with pancytopenia, dermatitis, and polyclonal gammopathy

A 73-year-old man developed conjunctivitis, epiphora, pancytopenia, dermatitis, and a polyclonal gammopathy. Diffuse infiltration and thickening of the conjunctiva and lacrimal canaliculi by plasma cells was present. Histopathologic examination suggested a reactive, chronic inflammatory response rather than neoplasia. The patient's ocular manifestations appeared to be related to his pancytopenia, dermatitis, and polyclonal gammopathy.     

Derivatives of apomorphine and of other N-substituted norapomorphines

Derivatives of apomorphine and of N-n-propylnorapomorphine were prepared to obtain modified pharmacological activity and enhanced chemical stability. Mouse profile and dog emesis screens were performed, and the activity of various N-substituted derivatives and their esters was evaluated and compared to the parent compounds. The N-n-propyl diacetate derivative and N-methyl and N-n-propyl ascorbate salts were remarkably stable to air: apomorphine etherate was no more stable than the free base. The dimers, the major products formed during the acid-catalyzed rearrangement of morphines to apomorphines, were all potent emetics. Additionally, two showed a significant antagonism to morphine in mice and dogs.     

Loxapine as an alternative to phenothiazines in a case of oculocutaneous skin pigmentation

The authors describe a patient with changes in oculocutaneous pigmentation that cleared after chlorpromazine was discontinued. They suggest that loxapine may be a suitable alternative to phenothiazines when skin pigmentation and ocular involvement occur, although the patient must be carefully monitored for ocular problems.     

Effect of 2,3,7,8-tetrachlorodibenzo-rho-dioxin on renal function in the rat

X-ray microanalysis of air dried and ultrathin frozen and frozen dried sections of human sperm cells has indicated a large deviation of elemental composition between cells in a single sample and between samples. Analysis of air dried cells indicates a similar subcellular elemental distribution to that found in sectioned material. Sodium to potassium ratios are found to be similar in both preparations. Air drying is considered a valid method for the preparation of sperm cells for analysis.     

Synaptic remodeling and free radical formation after brain contusion injury in the rat

The purpose of this study was to explore whether bilateral frontal cortex contusion in rats would demonstrate changes relevant for understanding the pathology of frontal lobe injury in humans. Rats were allowed to survive for 3, 7, or 18 days postinjury (dpi). In the contused rats, albumin was trapped in frontal cortices, as well as in other brain areas, showing that neurons were exposed to plasma components. In the sham-operated rats, which had only craniotomy but no penetration of dura, the level of trapped albumin was also increased compared to intact controls, suggesting a partial lesion-like condition. Choline acetyltransferase activity was severely decreased in the frontal cortices of contused rats, compared to the sham-operated controls. The decrease was most pronounced at 3 dpi and less pronounced 18 dpi, suggesting that after the initial damage, regeneration of the cholinergic terminals occurred. The concentration of the mature presynaptic membrane protein D3(SNAP-25) was also decreased in the frontal cortices of contused rats at 3 and 7 dpi, whereas it was normalized at 18 dpi. Previously, we have evaluated changes in the rate of synaptic remodeling in brain injury by calculating the ratio of the neural cell adhesion molecule (NCAM) to D3(SNAP-25). The NCAM/D3(SNAP-25) ratio at 3 dpi was elevated by more than 60% in the frontal cortices of contused rats, suggesting a high initial rate of synaptic remodeling. The ratios were smaller at 7 and 18 dpi, suggesting that after the initial burst, the rate of remodeling leveled off. In contrast, astrocyte activation was less pronounced at 3 dpi than at 7 and 18 dpi, as measured by the levels of glial fibrillary acidic protein and glutamine synthetase immunoactivities. The immunoreactivity of glutamine synthetase more than doubled in the contused brains but its enzymatic activity increased less than 50%, suggesting that many enzymatic centers had been inactivated by free radicals. Calculated as the difference between the relative immunoreactivity and the relative enzymatic activity the "lost glutamine synthetase activity" increased continuously in frontal cortex and striatum from 3 to 18 dpi, indicating the production of free radicals long after the initial contusion event. In conclusion, following frontal cortical contusions the early synaptic damage was partly compensated by synaptic remodeling. We suggest that the continuous production of free radicals may have contributed to the declining remodeling rate and impair functional recovery.     

Sharpness overconstancy in peripheral vision

Although much has been learned about the spatial sampling and filtering properties of peripheral vision, little attention has been paid to the remarkably clear appearance of the peripheral visual field. To study the apparent sharpness of stimuli presented in the periphery, we presented Gaussian blurred horizontal edges at 8.3, 16.6, 24, 32, and 40 deg eccentricity. Observers adjusted the sharpness of a similar edge, viewed foveally, to match the appearance of the peripheral stimulus. All observers matched blurred peripheral stimuli with sharper foveal stimuli. We have called this effect "sharpness overconstancy". For field sizes of 4 deg, there was greater overconstancy at larger eccentricities. Scaling the field size of the peripheral stimuli by a cortical magnification factor produced sharpness overconstancy which was independent of eccentricity. In both cases, there was a slight sharpness underconstancy for peripherally presented edges blurred only slightly. We consider various explanations of peripheral sharpness overconstancy.     

Aberrant cytokine expression and autocrine regulation characterize macrophages from young MRL+/+ and NZB/W F1 lupus-prone mice

We investigated whether macrophages (Mphi) from young, lupus-prone MRL+/+ and NZB/W F1 mice expressed common defects in immunoregulatory cytokine production. Endotoxin-activated Mphi from both strains, obtained well before disease signs, had a markedly reduced capacity to maintain IL-1 production compared with Mphi from normal strains (BALB/c, A/J, and C57BL/6). Mphi from lupus-prone mice showed similar defects in IL-6 and TNF-alpha production, which preceded the IL-1 defect. In fact, defective TNF-alpha production appeared to be responsible for aberrant expression of the other cytokines because this defect was the first to be expressed, and treatment with exogenous TNF-alpha reduced the extent of defective IL-1 and IL-6. These "proinflammatory" cytokine defects appeared to be selective because the anti-inflammatory cytokine IL-10 was not expressed aberrantly in the lupus-prone strains. For this reason, and because anti-IL-10 mAb treatment did not correct defective proinflammatory cytokine production, IL-10 did not appear to be responsible for these defects. IFN-gamma was able to normalize TNF-alpha production in Mphi from lupus-prone mice, demonstrating a stimulus-specific induction of the proinflammatory defects. These studies also revealed that Mphi from the three normal strains studied here maintain a precise inverse relationship between levels of TNF-alpha and IL-10, a relationship not seen in Mphi from lupus-prone strains. These findings reveal shared elements of cytokine dysregulation in the two principal animal models of multigenic lupus, and suggest that the study of Mphi (and perhaps other cells of the innate immune system) may provide valuable insights into intrinsic functional defects associated with systemic autoimmunity.