Familial adenomatous polyposis coli: five novel mutations in exon 15 of the adenomatous polyposis coli (APC) gene in Italian patients. Mutations in brief no. 225. Online

Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain-terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction-single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.     

Ultrastructural changes in nutritional cardiomyopathy of protein-calorie malnourished rats.

In this investigation, the ultrastructural features of the nutritional cardiomyopathy of protein-calorie-malnourished rats were examined. Protein-calorie malnutrition was induced in young rats by feeding them a low-protein diet (4% protein) for 6 weeks. Control animals were fed a high-protein diet (16% protein). The deficient rats showed severe restriction of body-weight gain, fatty liver and hypoproteinaemia. The results of the present study clearly demonstrated that the experimentally induced protein-calorie malnutrition brings about striking morphological changes in the heart of the rat. On light microscopy hyalinization an vacuolization of muscle fibres, loss of cross striations and myofibrils, small foci of necrosis, interstitial fibrosis and mononuclear-cell infiltration could be detected. The ultrastructural lesions were characterized by myofibrillar degeneration, contraction-band formation, dilatation of sarcoplasmic reticulum, mitochondrial swelling, dehiscence of intercalated discs, and widened interstitial spaces, especially around vessels, due to oedema fluid and cellular infiltration by mononuclear cells an activated fibroblasts with collagen fibres and microfibrils. In addition, an increase in relative heart weight was also observed. The potential role of catecholamines in the pathogenesis of this cardiomyopathy is discussed.     

Cascade filtration: clinical application in 26 patients with immune complex and IgM mediated diseases

A new technique which allows lymphocytapheresis to be combined with cascade filtration (CF) is described in this paper. This therapeutical approach was applied for the treatment of patients affected by necrotizing vasculitis (1), inflammatory myopathies (5), Cryoglobulinemia (5), immune complex polyneuropathies (7), rheumatoid arthritis (3) and psoriasis (3 patients). Two cases of Waldenstrom's macroglobulinemia were also treated after the onset of the hyperviscosity syndrome. 78 procedures have been performed without any untoward effect. From a clinical point of view all patients had some improvement following treatment, thereby confirming not only the clinical safety of this therapeutical approach but also its effectiveness at least in the management of diseases which usually respond to plasma exchange treatment. Laboratory investigations showed that with CF it is possible to selectively remove IgM, immune complexes, fibrinogen, lipoproteins and high molecular weight plasma components, sparing most albumin and IgG globulins (85 and 71%, respectively).     

Fungus colonisation of pulmonary rheumatoid nodule

This report describes a 69 year old woman, suffering from active rheumatoid arthritis since the age of 60 and presenting with severe dyspnoea and cough. A computed tomography scan of the chest showed multiple bilateral pulmonary nodules, sometimes cavitated, associated with reticular opacities and pleural effusion. A videothoracoscopic excision of a cavitated nodule was performed. Seven days after surgery, a right pneumothorax developed, and the patient died of septicaemia one month later. Microscopically, the excised nodule was composed of necrotic fibrinoid material with a peripheral rim of palisaded histiocytes, extending to the pleural surface and containing several fungal hyphae morphologically consistent with aspergillus. A diagnosis of pulmonary rheumatoid nodule with fungus colonisation was made. In the lung, fungus colonisation is a rare complication of rheumatoid nodules. The most important differential diagnostic considerations are briefly discussed.     

Characterization of a bovine collagen-hydroxyapatite composite scaffold for bone tissue engineering

Different biomaterials have been used as scaffolds for bone tissue engineering. Here we characterize a biomaterial composed of sintered (1100 degrees C) and powdered hydroxyapatite (HA) and type I collagen (Coll), both of bovine origin, designed for osteoconductive and osteoinductive scaffolds. Coll/HA proportions were 1/2.6 and 1/1 (wet weight), and particles sizes varied from 200 to 400 microm. Vv (volume density) and Sv (surface to volume density) for the HA particles in the composite ranged from 0.48 +/- 0.06 to 0.55 +/- 0.02 and 5.090 +/- 0.545 to 6.366 +/- 0.289 microm(-1), respectively. Due to the relatively small changes in Vv and Sv, a macroporosity could be characterized for the biocomposite. X-ray diffraction and infrared spectroscopy showed that the sintered bone was composed essentially of HA with minimum additional groups such as surface calcium hydroxide, surface and crystal water, free carbon dioxide and possibly brushite. Mass spectrometry detected carbonates at A and B sites of HA, and weakly bound to the structure. Human osteoblasts adhered and spread on both the HA particle surface and the collagen fibers, which seemed to guide cells between adjacent particles. The biocomposite studied has several characteristics considered as ideal for its use as a scaffold for osteoconduction and osteoinduction.     

Identification of very early lymphoid precursors in bone marrow and their regulation by estrogen

Estrogen is a negative regulator of lymphopoiesis and provides an experimental tool for probing relationships between lymphocyte precursors and stem cells. We found that expression of lymphocyte-associated genes and immunoglobulin (Ig) gene rearrangement occurred before CD45R acquisition. Lymphoid-restricted progenitors that were Lin(-)IL-7R alpha(+)c-kit(lo)TdT(+) (lineage marker(-), interleukin receptor 7 alpha(+), c-kit(lo) and terminal deoxynucleotidyl transferase(+)) were selectively depleted in estrogen-treated mice; within a less differentiated Lin-c-kit(hi) fraction, functional precursors of B and T, but not myeloid, cells were also selectively depleted. TdT and an Ig heavy chain transgene were detected within a hormone-regulated Lin(-)c-kit(hi)Sca-1(+)CD27(+)Flk-2(+)IL-7R alpha(-) subset of this multipotential progenitor population. Identification of these extremely early lymphoid precursors should facilitate investigation of the molecular mechanisms that control lineage-fate decisions in hematopoiesis.     

Hemispheric control of unilateral and bilateral responses to lateralized light stimuli after callosotomy and in callosal agenesis

Normally, simple digital or manual responses to a light stimulus in the right or left visual hemifields are performed faster with uncrossed hand-field combinations than with crossed hand-field combinations. Because of the organization of visual and motor pathways, the integration of uncrossed responses is assumed to occur within a single hemisphere, whereas a time-consuming inter-hemispheric transfer via the corpus callosum is considered to be necessary for the integration of crossed responses. However, callosal transfer may be dispensable for those crossed responses which can be controlled through ipsilaterally descending motor pathways by the hemisphere receiving the visual stimulus. We investigated crossed-uncrossed differences (CUDs) in speed of simple visuomotor responses to lateralized flashes in one subject with total section of the corpus callosum and two subjects with complete callosal agenesis. We recorded the reaction times as well as the premotor times, as indicated by the electromyographic latencies of the prime movers, of three types of responses: a distal response involving a thumb flexion, a proximal response chiefly involving a forearm flexion and an axial response involving a shoulder elevation. Further, the three types of responses to a single lateralised flash were performed both unilaterally and bilaterally. The three acallosal subjects showed CUDs greatly exceeding normal values on distal responses, either unilateral or bilateral, and on unilateral proximal responses. These abnormally long CUDs stood in sharp contrast to the insignificant CUDs exhibited by the same subjects on bilateral proximal responses and on unilateral and bilateral axial responses in agreement with correspondingly insignificant CUDs reported for normal subjects. These results confirm that a callosal contribution is important for the execution of fast distal and unilateral proximal responses to a visual stimulus directed to the hemisphere ipsilateral to the responding hand. By contrast, the other types of crossed responses appear to be efficiently coordinated across the midline without the aid of the corpus callosum. This is in keeping with the hypothesis that they are governed by a bilaterally distributed motor system which is preferentially activated for the execution of symmetrical bilateral movements, employing axial and proximal limb muscles.     

Serological survey of human immunodeficiency virus (HIV) in Ethiopia

The presence of anti-human immunodeficiency virus 1 antibodies was tested in 5,565 serum samples from Ethiopia of which 5,265 were collected from military recruits in the framework of a hepatitis B (HBV) seroepidemiological study performed on a national scale in 1985-1986; the remaining were 300 sera from a population of outpatients belonging to the Arsi region. Of the 5,565 sera, 121 (2.1%) were found to be repeatedly reactive by enzyme-linked immunosorbent assay (ELISA) test for HIV-1 antibodies, but these reactivities were confirmed by Western Blot (WB) assay in only four cases (0.07%) and by ENVACOR (confirmatory competitive ELISA) in three samples. Twenty-three sera were positive by WB to one or two bands related to core proteins but were all negative by ENVACOR. However, according to accepted criteria for positivity, these sera must be regarded as indeterminant reactors. A sample of 409 sera, both reactive and nonreactive by HIV-1 ELISA, were further tested for antibodies to HIV-2 by ELISA. Reactive sera were analysed by WB and by radioimmunoprecipitation assay (RIPA) using 35S-cysteine metabolically labelled SIVmac (HTLV-IV) infected cell lysates. Only 11 sera were found to be slightly reactive in ELISA, but this was not confirmed by WB or RIPA. Data indicate that HIV infection was not widespread in the general population of Ethiopia up to 1986.