Eruptive syringomas with calcium deposits in a young woman with Down's syndrome.

Eruptive syringomas are uncommon in the general population. We describe here an 18-year-old female, affected by Down's syndrome, who presented with an abrupt eruption of small skin-colored or reddish papules on the face, neck and limbs. Light microscopy allowed us to diagnose syringomas, whereas the study of the ultrastructural features revealed calcium deposits in many lumina and also in the mitochondria. This observation confirms the hypothesis that the syringeal structure plays a role in the pathogenesis of calcinosis cutis.

Chronic heat-induced skin lesions (erythema ab Igne): ultrastructural studies.

Erythema ab igne (EI) is an uncommon skin lesion caused by mild and repeated exposure to infrared sources. The aim of this study was to investigate the ultrastructural alterations in this condition. The ultrastructural study was carried out on 5-outpatients who presented typical EI of their exposed sites. Skin punch biopsies were processed for standard electron microscopy. The epidermis was hyperpigmented, with focal regressive changes of basal keratinocytes. An apparent functional activation of melanocytes with numerical increase of dendritic processes was also observed. The dermis showed abundant melanophages and occasional elastic fiber alterations similar to actinic elastosis. No alterations consistent with preneoplastic skin conditions were observed. The ultrastructural findings associated with EI seem to be nonspecific and consistent with moderate regressive changes of keratinocytes as well as a consensual melanocytic activation and elastic fiber modifications. Similar alterations can be observed in chronic actinic skin damage. This condition is presumably more benign than the ultraviolet exposure. The association of EI and premalignant skin lesions, though occasionally described, seems relatively infrequent.

Primary macular amyloidosis: an ultrastructural approach to diagnosis.

Seven cases of primary macular amyloidosis were studied on skin biopsies. The Congo red stain was positive only in three cases, whereas the ultrastructural observation allowed for the detection of amyloid deposits in all biopsies. Fibrillary degeneration of basal keratynocytes was occasionally observed, and regressive changes of keratynocytes and dermal nerve bundles presumably related to the intensity of the scratch trauma were detected in one case. In six biopsies mast cell profiles exhibiting various degrees of degranulation were detected in the dermis. Melanosome aggregates were also observed consistently in dermal macrophages and occasionally in Schwann cells. A variable degree of structural alteration was observed in dermal unmyelinated nerve fibers. Even if the intimate mechanism of amyloid deposition was not explained by the ultrastructural study, this approach is a useful instrument in the differential diagnosis of cutaneous macular hyperpigmented lesions.

Cytotoxic effects of high energy shock waves on cancer cells linked to metallic beads vehicled by monoclonal antibodies.

Previous studies have reported that high energy shock waves (HESW), generated by an electrohydraulic lithotriptor, may have some utility as a cancer treatment modality. Furthermore, it has been described that shock waves propagating in a fluid, show demolitive effects at the level of the interface of a solid fragment immersed in the fluid. In this study, we demonstrate that it is possible to enhance the antineoplastic effects of HESW if treated cells or tissues are linked to monoclonal antibodies (MoAbs) conjugated with metallic beads (MB) (about 1 mu of diameter) and specific for a cancer cell surface determinant. A leukemic cell line was used to study the effects of HESW on cells linked to MB. A fresh human breast cancer specimen was used to perform the assay on tumor tissue. MB linked treated cell viability, growth curve, cloning efficiency and Bromodeoxyuridine incorporation were reduced in comparison to cells treated with HESW alone. Our data suggest that the presence of solid fragments vehicled by MoAbs on a cancer cell surface is able to synergize with the limited antineoplastic effects of HESW.

Time-related ultrastructural changes in an experimental model of whole brain irradiation.

To stimulate therapeutic irradiation, we exposed rats to conventional fractionation (200 +/- 4 cGy/d, 5 d/wk; total dose, 4000 cGy). The effects of this regimen were assessed by electron microscopic examinations of brain microvascular and parenchymal cells 15 and 90 days after irradiation. Studies of the transendothelial passage of horseradish peroxidase provided information about the functional status of the blood-brain barrier. At 15 days after irradiation, there was an increased vesicular transport of horseradish peroxidase across the intact endothelium without opening of the tight junctions, and without evidence of structural alterations of neuropil, neuronal bodies, and astrocytes. Ninety days after irradiation, well-defined ultrastructural alterations were observed, involving the microvasculature, the neuropil, the neuronal bodies, and astrocytes. The main ultrastructural feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Altered neurons and reactive activated astrocytes were also noticeable. These data suggest a possible association, not necessarily causal, between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain toxicity.

Progressive perturbations in cerebral energy metabolism after experimental whole-brain radiation in the therapeutic range.

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation have not been fully elucidated in the literature. The authors employed the [14C]-2-deoxy-D-glucose autoradiography method to investigate the effect of whole-brain x-irradiation on local cerebral glucose utilization in the rat brain. The animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week for a total dose of 4000 cGy), and the effects of this regimen were assessed at 2 weeks and 3 months postirradiation. In rats evaluated 2 weeks after treatment, statistically significant decreases in cerebral metabolic activity were found in 13 of the 27 regions studied, compared to control animals. In rats studied 3 months after treatment, additional metabolic suppression and statistically significant decreases in cerebral metabolic activity were found in 11 of the 27 regions, compared to rats studied 2 weeks after treatment. A weighted-average rate for the brain as a whole was approximately 15% and approximately 25% below that of control animals 2 weeks and 3 months after exposure, respectively. Although the difference in species is significant enough so that direct extrapolation to humans may not be appropriate, the data reported here may have potential clinical implications for the evaluation of the risk-benefit ratio for radiotherapy. This model can be used reproducibly for further investigations, including evaluation of therapies that may reduce irradiation-induced brain injury.

Circadian rhythm of glucose utilization in the pineal body of rats of different ages.

Employing quantitative autoradiography, pineal body glucose utilization (GU) was measured in daytime or at night in prepubertal (aged 1 month), adult (aged 3 months), and mature (over 12 months old) rats. In prepubertal and adult rats, in daytime, GU values within the pineal tissue were homogeneously distributed around 65 mumol glucose/100 g per min. In prepubertal animals no significant variations in GU were observed between daytime and nocturnal measurements. A circadian metabolic rhythmicity was evident in adult rats, with a GU peak measured at 2 a.m. In mature animals, GU also varied between day and night, with an increment in the relative difference between the two values. The present investigation is the first to demonstrate that circadian metabolic rhythmicity is absent before sexual maturation while it is enhanced in 12-month-old rats. These changes in pineal energy metabolism with advancing age are intriguing in view of the concept that the pineal gland may be involved in functional changes occurring during the process of aging.

Quantitative study of blood-brain barrier permeability changes after experimental whole-brain radiation.

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation are not known precisely. We investigated the possibility of a change in blood-brain barrier (BBB) function as a causative factor for early delayed whole-brain radiation-induced cerebral dysfunction. Rats were exposed to conventional fractionation (200 cGy/d, 5 d/wk; total dose, 4000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid technique and electron microscopy. Studies of the passage of horseradish peroxidase across the BBB permitted comparative quantitative isotopical and qualitative morphological data. Experiments were carried out 2 to 3 weeks after the completion of the radiation exposure. The transport of 14C-alpha-aminoisobutyric acid across the BBB increased significantly in cerebral cortex and cerebellar gray matter, averaging 1.3 to 1.5 times over the normal values. Electron microscopy disclosed an intense vesicular response of the cortical microvascular endothelium that occurred without the opening of the tight junctions and resulted in an intense transport of HRP across the intact endothelium. The present data indicate that moderate doses of whole-brain radiation induce well-defined changes in BBB function, which possibly are involved in the pathogenesis of radiation-induced cerebral dysfunction in humans.

Effect of whole brain radiation on local cerebral glucose utilization in the rat.

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week; total dose, 4000 cGy). Metabolic experiments were made 2 to 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased after irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, the brain areas with the highest basal metabolic rates showed the greatest percentage of decrease in glucose utilization. The concept that radiation suppresses glucose utilization before any morphological change takes place in the cell structures was the basis of this study. Metabolic alterations after irradiation may explain the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy. These studies have applications to observations made with the [18F]-fluorodeoxyglucose method in conjunction with positron emission tomographic scans in patients receiving radiation therapy for intracranial malignancies. The data reported here also have potential clinical implications for the evaluation of a risk/benefit ratio for radiotherapy in patients with benign neurosurgical diseases or children undergoing prophylactic treatment of the central nervous system.

Effect of x-radiation to brain on cerebral glucose utilization in the rat.

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.

Development of the pigeon bursa of Fabricius. A scanning and transmission electron microscope study.

The development of the pigeon bursa of Fabricius was investigated by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Particularly SEM emphasized that the bursa during development progressively undergoes hypertrophia and hyperplasia of lobules constituting the plicae. Moreover modifications of surface epithelium were observed. During early days of development after hatching, epithelium showed evenly distributed microvilli which become shorter and shorter and also unevenly distributed with aging. In addition TEM allowed us to state that the bursa of Fabricius in pigeons, during development, undergoes morphological modifications among which one of the most remarkable is the gradual and continuous increasing of lymphocytes. Another one, as it was already observed in chickens (Frazier 1974), consists in the contemporaneous but independent development of cortex and medulla, even if we observed undifferentiated epithelial cells moving from medulla to cortex and a migration of lymphocytes and mesenchymal cells from cortex to medulla (Tar et al. 1958; Ackerman et al. 1964; Naukkarinen et al. 1978).

Experimental modification of the growth of the bursa of Fabricius in chickens revealed by scanning and transmission electron microscopy.

The ultrastructural changes occurring in the bursa of Fabricius of 3 and 7 d old chickens after adriamycin treatment are described. Male Hubbard chickens 7 d old, were injected with a intraperitoneal injection of adriamycin (5 mg/kg/die). All chickens were killed 24 h after the last injection, and the bursa was rapidly excised and fixed immediately for scanning electron microscopy and for transmission electron microscopy. The bursa underwent atrophy and showed epithelium desquamation. After 6 d treatment the dysepithelization was evident. Consequently follicles were made up mostly with large polyedric cells.