Cesare Bosman

Neuromyopathy and restrictive cardiomyopathy with accumulation of intermediate filaments: a clinical, morphological and biochemical study

SummaryThe clinical, morphological and biochemical findings of a sporadic case, showing accumulation of desmin-type intermediate filaments in skeletal muscle and myocardium are described. Desmin storage was demonstrated by immunofluorescence, sodium dodecyl sulfate gel electrophoresis and two-dimensional gel electrophoresis. These findings are in agreement with those of Rappaport et al. (FEBS Lett. 231:421–425, 1989). A sensory-motor polyneuropathy was established by electrophysiological studies and, ultrastructurally, intramuscular nerves showed accumulation of neurofilaments and neurotubules with formation of axonal spheroids. These findings are discussed considering all previous reports with related conditions.

Spindle cell (Kaposiform) hemangioendothelioma with Kasabach‐Merritt syndrome in an infant: Successful treatment with α‐2A interferon

A two-month-old infant developed a vascular tumor of the right flank which upon biopsy proved to be a spindle cell hemangioendothelioma. The increased capillary bed characterizing the neoplasm caused a severe thrombocytopenia together with a consumption coagulopathy (Kasabach-Merritt syndrome). The patient, who was dependent on platelet transfusions, improved quickly after interferon alpha-2a was given at the dosage of 3,000,000 U/m2, with resolution of the Kasabach-Merritt syndrome after three weeks and a 75% decrease of the tumor volume within three months of treatment.

Mechanisms of Osteoclast Dysfunction in Human Osteopetrosis: Abnormal Osteoclastogenesis and Lack of Osteoclast-Specific Adhesion Structures

Osteoclasts from a patient affected by osteopetrosis were examined in vivo and in vitro. Iliac crest biopsy revealed an osteosclerotic pattern, with prominent numbers of osteoclasts noted for hypernuclearity and incomplete adherence to the bone surface. A population comprising tartrate‐resistant acid phosphatase (TRAP)‐positive, multinucleated and mononuclear cells, and alkaline phosphatase‐positive stromal fibroblasts was obtained in vitro from bone marrow. Mononuclear TRAP‐positive precursors spontaneously fused in culture to form giant osteoclast‐like cells. These cells expressed the osteoclast marker MMP‐9 and calcitonin receptor, and lacked the macrophage marker, Fc receptor. Expression and distribution of c‐src, c‐fms, and CD68, and response to steroid hormones relevant to osteoclast differentiation and function were apparently normal, whereas cell retraction in response to calcitonin was impaired. TRAP‐positive multinucleated cells did not form osteoclast‐specific adhesion structures (clear zone, podosomes, or actin rings). Bone resorption rate was severely reduced in vitro. Focal adhesions and stress fibers were observed en lieu of podosomes and actin rings. Adhesion structures contained low levels of immunoreactive vitronectin receptor, most of this integrin being retained in cytoplasmic vesicles. These data provide the first characterization of abnormal differentiation and function of human osteopetrotic osteoclast‐like cells.

Cardiomyopathy and multicore myopathy with accumulation of intermediate filaments

A girl affected by a restrictive cardiomyopathy with neuromuscular involvement is described. Morphological examination showed a pattern of multicore myopathy and with electron microscopy a sarcoplasmic accumulation of electron dense granular and filamentous material was demonstrated both in skeletal muscle and heart. This peculiar electron dense material corresponded to increased desmin in muscle and cardiac fibres and was demonstrated immunohistochemically.

Oxidation of diphenyl diselenide with ceric ammonium nitrate: a Novel route for functionalization of olefins

Abstract Alkenes were reacted with diphenyl diselenide in presence of ceric ammonium nitrate in methanol, affording β-methoxyalkyl phenyl selenides in good yields.

Detection of virus-like particles in liver biopsies from HCV-infected patients

In order to directly ascertain the presence of HCV virus infection in livers of patients with HCV chronic hepatitis, we investigated, by transmission electron microscopy (TEM), liver biopsies from 2 adults and 4 children for the presence of virus-like particles (VLPs). The plasmas of these HCV-positive patients were HCV-RNA-positive, with high ALT values. In liver tissue samples examined, we were able to detect plus and minus strands of HCV RNA by strand-specific RT-PCR. Aggregates or single VLPs of about 45 nm in diameter were detectable in variable amounts in endoplasmic cisternae and in hepatocyte cytoplasms of infected patients. These results emphasize the relevance of performing TEM assays to confirm the diagnosis of HCV infection.

A histologic and flow cytometric study of Kaposi's sarcoma

Cine hundred forty‐three biopsies of Kaposis sarcoma (KS) from 96 patients were assessed histopathologically, and mitoses were counted. Ninety‐seven samples from 66 patients were analyzed by flow cytometry. Six of 97 (5.8%) KS lesions were DNA aneuploid with a clustering around a DNA index of 1.5 (range, 1.4 to 1.6). The median percentage of S‐phase plus G2‐phase cells (%S + G2) was 16.7%. Increasing mitotic counts and %S + G2 were seen with progression of the phase and pattern of disease. Nodular KS and spindle cell predominant KS had the highest mitotic counts and %S + G2, with nodular KS larger than 4 mm having a higher mitotic count than those smaller than 4 mm. These findings suggest a low level of DNA ameuploidy in KS and important changes in the level of cell proliferation with the phase and pattern of the disease. However, flow cytometry does not solve the dilemma of whether KS is a hyperplastic or neoplastic process.

Morphology of the atrioventricular valve in asplenia syndrome: A peculiar type of atrioventricular canal defect

The high risk of atrioventricular (AV) valve regurgitation is a major point of concern in the natural history of patients with atrioventricular canal defect (AVCD) and asplenia syndrome (AS). The morphology of the common AV valve in patients with AVCD and AS was therefore studied and compared with the anatomy of patients with AVCD but with atrial situs solitus. We compared the anatomic features of hearts with common AV valve (ventricular loop; AV valve alignment on ventricles; number of leaflets; number and morphology of papillary muscles and relationship of the bridging leaflets with the ventricular septum) in the hearts of 33 patients with AVCD and asplenia syndrome (Group 1) with those of 44 patients with common AV valve, complete AVCD, and atrial situs solitus (Group 2). Hearts featuring asplenia syndrome showed a significantly higher occurrence of anomalies of the ventricular loop (p < .0001), right ventricular dominance (p < .01), and a reduced number of valvular leaflets and papillary muscles (p < .0005). On the contrary, hearts with situs solitus of the atria showed a significantly higher frequency of balanced ventricles (p < .0001) and a common AV valve with five leaflets and five papillary muscles (p < .000001). These data suggest that AVCDs in association with asplenia syndrome present morphologic peculiarities that may be considered as the substrate for the abnormal regurgitation. Recognizing the presence of these features could be of great value for the planning of a specific surgical treatment. These anatomic differences support the hypothesis of a genetic heterogeneity of AVCDs.

Congenital-infantile fibrosarcoma: study of two cases and review of the literature.

Background Congenital-infantile fibrosarcoma is a rare tumor of the pediatric age. It involves subjects under 5 years of age, and more than 200 cases have been reported in the literature. Methods The authors present the clinicopathologic findings of 2 cases and review the literature. Results Of our 2 patients, the first was a 2-years and 6-months-old female and the second a newborn male. The female presented a tumor in the retroperitoneum without recurrences or metastasis after 17 months, and the male on left foor with a recurrence after 3 months. Histologically, the tumors were mainly composed of spindle-shaped cells. Immunohistochemically, in both cases, neoplastic cells were positive for vimentin; focal positivity for muscular specific actin was present in the tumor of the female. Ultrastructurally, tumors were composed of mesenchymal cells with fibroblastic and myofibroblastic features. Flow cytometric analysis of the retroperitoneal tumor showed an aneuploid population of neoplastic cells. Conclusions Congenital-infantile fibrosarcoma should be considered a borderline tumor; its biologic behavior is better than that of adult fibrosarcoma. Histologic diagnosis is not easy; the microscopic picture may be confused with fibromatosis or with malignant mesenchymal neoplasms. Only a follow-up of many years can confirm the benignancy or malignancy of any individual tumor, even though clinico-pathologic features may be distinctive enough to permit its recognition.

Pathologic features in two siblings with the Pena-Shokeir I syndrome

Two siblings whose clinical and pathologic features were consistent with the “Syndrome of camptodactyly, multiple ankyloses and pulmonary hypoplasia” originally described by Pena and Shokeir were examined at autopsy. Additional features were intrauterine growth retardation, immaturity of the central nervous system (CNS) and atrophy of skeletal muscles. Our data suggest that CNS damage may cause the complicated phenotypic abnormalities of the syndrome.