Acetaldehyde, ethanol and acetone concentrations in blood of alcohol-treated mice receiving aldehyde dehydrogenase-loaded erythrocytes.

Blood levels of acetaldehyde (ACh), ethanol and acetone were investigated in mice treated with ethanol for 6 months and receiving compatible erythrocytes (RBCs) overloaded with aldehyde dehydrogenase (AlDH). Following an acute dose of ethanol, ACh levels were significantly lower in these animals than in alcohol-treated mice receiving AlDH-unloaded RBCs, and were similar to the ACh levels of normal mice. The peak ethanol concentration was higher in normal mice than in both groups of alcohol-treated animals, while acetone concentrations were not significantly different in the three groups of animals.     

MRI, antibody-guided scintigraphy, and glucose metabolism in uveal melanoma.

To evaluate the usefulness of structural and biochemical imaging techniques for the diagnosis of uveal melanoma, 12 patients with choroidal melanoma were examined. Magnetic resonance imaging was used in 11 of 12 patients, as one had a metal prosthesis. All the subjects underwent single photon planar scintigraphy (SPPS) and single photon emission computed tomography (SPECT) using the 99mTc-labeled F(ab')2 of the anti-melanoma monoclonal antibody 225.28S ([99mTc]MoAb) and positron emission tomography (PET) using [18F]fluorodeoxyglucose ([18F]FDG). Magnetic resonance identified 6 of 11 melanotic lesions (definite melanomas) and 4 of 11 hypomelanotic lesions (probable melanomas), whereas in one case it was inconclusive. [99mTc]MoAb uptake was observed in 5 of 12 lesions using SPPS and 8 of 12 lesions using SPECT. [18F]FDG uptake was observed in 3 of 12 lesions by PET. These results demonstrate that both MR and radioimmunoscintigraphy are sensitive techniques for the diagnosis of choroidal melanomas and suggest that the detection of melanomas by MR, SPPS, and SPECT is largely dependent upon their size. The validity of these conclusions was verified in four subjects in whom the diagnosis was based on MR and/or SPECT findings only and confirmed by histology. The finding that only some of the uveal melanomas of larger size are visualized based on [18F]FDG uptake suggests that melanomas can have either high or low glucose consumption.     

A Case of Hypopigmented Mycosis Fungoides in a Young Caucasian Boy

Abstract: Hypopigmented mycosis fungoides is a variant of mycosis fungoides characterized by the presence of hypopigmented patches as the sole manifestation of the disease. It has been described aimost always in young black or dark-skinned patients. The only white patient described was a 64-year-oid woman who not oniy had hypopigmented lesions, but also nodular lesions with lymphadenopathy. We describe hypopigmented lesions arising in a white boy 12 years of age, born in northern Italy, without any foreign ancestors. The microscopic alterations, with epidermotropism, the immunoiogic markers, the negativity of T-cell receptor gene rearrangement, and the good response to PUVA therapy correspond to the main findings in black patients with this disease. Long-term follow-up of these patients is important to obtain better knowledge of the natural history of the disorder, Hypopigmented mycosis fungoides must now be included in the differential diagnosis of hypopigmented macular lesions not only in black or dark-skinned patients but also in white patients.     

Limb reduction defects in Emilia Romagna, Italy: epidemiological and genetic study in 173,109 consecutive births.

Epidemiological and genetic variables in limb reduction defects (LRD) were analysed during the years 1978 to 1987 in a case control study in Emilia Romagna, northern Italy. During the observation period, 83 neonates out of 173,109 consecutive births had LRD (4.8 per 10,000). Cases were divided into five subgroups: transverse, intercalary, longitudinal, split, and multiple types of LRD. Of all cases, 64% were upper limb, 21% lower limb, and 15% both. Coexisting non-limb malformations were found in 10 cases (12%), five with recognised syndromes and five with other associated defects. About 7.2% of first degree relatives had defects involving the skeletal system. In two cases the mother had the same type of LRD (a split). No recurrence among sibs was observed. Risk factors correlated with LRD were found to be low birth weight (2500 g or less), vaginal bleeding, and threatened abortion.     

New treatment protocol including lympholytic and antiretroviral drugs to inhibit murine AIDS

Highly active antiretroviral therapy (HAART), although very efficient in reducing viral load to undetectable levels within 2 weeks, does not eradicate HIV-1 infection and after the suspension of therapy, HIV RNA rebounds to pretherapy levels. This limited efficacy is mainly due to the existence of viral reservoirs such as CD4+ T cells, macrophages, and dendritic cells in which the virus can remain latent. Elimination of these latent reservoirs would be a possible solution to this problem and various efforts are now being directed to this end. With this goal in mind, we investigated a lympholytic drug with known activity against lymphoproliferative malignancies, 2-fluoro-ara-AMP (fludarabine). The murine model of AIDS was used to evaluate the efficacy of alternating administration of fludarabine and azidothymidine (AZT). The aim of this experiment was to eliminate infected cells with fludarabine and protect noninfected cells with AZT. LP-BM5-infected mice were treated with two different therapeutic protocols: one group was treated with two alternating 3-week cycles of fludarabine and AZT (treatment A), whereas the other was treated with three alternating 2-week cycles of fludarabine and AZT (treatment B); both treatments lasted 12 weeks and the animals in the two groups received the same amount of drug. At different times of infection, disease-related findings (i.e., splenomegaly, lymphadenopathy, hypergammaglobulinemia, T-cell and B-cell spleen cell proliferative index, and phenotypes of peripheral blood lymphocytes) were analyzed and the content of proviral DNA in the lymph nodes was quantified. The results obtained show that treatment B was more effective in inhibiting disease progression than treatment A. In fact, all parameters investigated were almost within control values. These results were also confirmed by the quantification of proviral DNA content in the lymph nodes, which after 12 weeks of treatment A declined by approximately 50%, whereas treatment B decreased proviral DNA content by approximately 85% with respect to infected/untreated mice. The data obtained suggest that a therapeutic protocol including three cycles rather than two of a lympholytic drug and antiretroviral drugs is more advantageous. The efficacy of the treatment could likely increase if other drugs were used in addition to AZT and more cycles of fludarabine were added. This approach appears to be of potential interest in an HIV-1 eradication protocol.     

Functional evaluation of the basophil/IgE system in the cord blood

Basophil releasability was studied in 24 cord blood samples from normal-term deliveries. The histamine content in cord blood basophils was similar to that of adult blood basophils. The response to IgE-independent degranulating stimuli such as calcium ionophore A23187 and zymosan-activated human serum was overlapping with that of normal adults. Conversely, a reduced releasability was observed after challenge with anti-IgE, even after sensitization with an IgE-rich serum. The IgE-dependent degranulation seems to be hampered by the low concentrations of circulating and cell-bound IgE antibodies. The number of IgE molecules bound to the specific receptors in cord blood basophils is significantly lower than in adult blood basophils.     

The extracellular matrix of healthy and atretic mouse ovarian follicles studied by lanthanum nitrate and polycation ruthenium red

Changes occurring in the fine structure of Zona pellucida and follicular fluid in growing and atretic follicles in mice were examined by electron microscopy using lanthanum nitrate and ruthenium red. The results showed that follicular fluid has a dense globular aspect in growing follicles but becomes more dispersed and globular-fibrillar in atretic follicles. It is formed by rounded negatively charged particles (20 nm in diameter) that are closely packed in growing follicles, but spaced and united by filaments in atretic follicles. These changes may be related to a changed role of granulosa cells and also to an altered passage of nutritive substances from the plasma into the follicle. The Zona pellucida is intensely colorable only in the atretic follicles, where it is composed of a dense globular fibrous matrix, but not in growing follicles, where it reveals a weak reaction with ruthenium red. While in the Zona pellucida of growing follicles the globular negatively charged particles (20 nm in diameter) probably due to sialic acid moieties are rarely evident, these particles become highly numerous and connected by microfilamentous structures in atretic follicles. The altered electrical charge of polyanions may reflect a different chemical permeability of the Zona pellucida. Then the increase of negative charged particles in the zona may have a role in a process of sequestration of the oocyte during atreasia.     

Intertubular capillary changes in kidney allografts: a morphologic investigation on 61 renal specimens.

A total of 61 kidney allograft specimens (51 biopsies and 10 nephrectomies) from 44 patients were investigated. Transplant glomerulopathy (TGP) was found in 38 specimens. Electron microscopy disclosed peculiar intertubular capillary changes (ITCC) in 47 specimens (all those showing TGP and nine without TGP). They were characterized by splitting and multilayering of the basement membranes. TGP and ITCC were graded and found mild (in 23 and 22 specimens), moderate (in 11 and 16 specimens), and severe (in four and nine specimens). Both worsened with time lapse from transplantation. When both were compared in single specimens, their grading was similar or, with a few exceptions, more severe for ITCC. TGP and ITCC were more frequent in biopsies with morphologic evidence of rejection and less frequent in patients treated with Cyclosporine A. Repeated biopsies and nephrectomies were studied in 10 patients and a somewhat more precocious appearance of ITCC than of TGP was found. Earlier and more severe ITCC were found in two patients who had had two transplants as compared to those with one. Morphologic similarities between TGP and ITCC suggest a common pathogenetic mechanism related to endothelial damage. The association to the histological evidence of rejection as well as the apparently protective activity of Cyclosporine A could support the involvement of an immune-mediated mechanism in agreement with what is reported in literature. The constant association of ITCC and TGP and its possible more precocious appearance enforce the diagnostic value of the former, which allows to infer the presence or the subsequent development of TGP even in biopsies where glomeruli are lacking.     

Variation of the spatial position computed by Roentgen Stereophotogrammetric Analysis (RSA) under non-standard conditions

Roentgen Stereophotogrammetric Analysis (RSA) has been applied to different kinds of research in order to obtain important information in the biomechanics field. Operative requirements change according to the type of investigation and sometimes practical conditions do not always permit one to respect standard specifications. The aim of this paper is to verify the reliability of the system under non-standard conditions, studying the effects of the focus-to-film distance on the determination of 3D co-ordinates of markers. The application of statistical analysis, consisting of two and three way ANalysis Of VAriance (ANOVA), showed that focus-to-film distance is not a significant source of variation, i.e., the system can correctly compute the marker position inside the calibrated space under all conditions of magnification. Since we obtained a fluctuation due to focal distance change of 10(-5) mm (LSD for 95% confidence level), we can assert that this source causes a variation strictly within the limits required by clinical investigations. Thus, this study contributes to improving the flexibility of RSA in clinical applications, making the technical requirements of the radiographic set-up less constraining.