Disappearance of molsidomine effects on pulmonary circulation of patients with chronic obstructive pulmonary disease after a three week treatment

The effect of oral molsidomine (M) on the pulmonary artery hypertension of patients with chronic obstructive pulmonary disease (COPD) was investigated during an acute study (4 mg once) and after a 3 week-treatment (3 times 4 mg a day), on a double-blind basis in 16 patients, 8 receiving a placebo, and 8 molsidomine. Ventilatory and cardiocirculatory indices were obtained at rest and during exercise. When acutely given, molsidomine reduces the mean pulmonary arterial pressure (PAP), the pulmonary vascular resistance (PVR) and the arterial O2 partial pressure (PaO2), increasing heart rate (HR) as well as the alveo-arterial O2 partial pressure difference (P(A-a)O2). During exercise, pulmonary arterial pressure and pulmonary vascular resistance decrease while heart rate increases without modification of arterial blood gases. After a 3-week treatment, molsidomine no more improves any index but significantly reduces cardiac output during exercise and consequently the O2 delivery to the tissues. The same feature has already been observed for other nitrates. It thus seems inappropriate to prescribe nitrates or nitrate-like drugs to chronic obstructive pulmonary disease patients with a view to lower their pulmonary hypertension.     

Intermediate filaments in smooth muscle tumours

Antisera to the intermediate filaments vimentin and desmin react with fixed paraffin embedded tissue. Benign uterine myomas contain both classes of filaments. Gastrointestinal "smooth muscle tumours" however often lack desmin even when they appear histologically benign. In the sarcomas examined vimentin was the only class of intermediate filament present. The diagnostic and histogenetic implications of these findings are discussed.     

Lymphoma-like presentation of acute monocytic leukaemia

Four patients in whom a diagnosis of acute monocytic leukaemia (M5) was subsequently made presented with extramedullary disease clinically resembling lymphoma. In all patients histological sections were initially misinterpreted as showing malignant lymphoma or anaplastic carcinoma. The diagnosis of M5 leukaemia was subsequently made on the basis of morphological and cytochemical studies of peripheral blood and bone marrow. The histological diagnosis of the soft tissue lesions of M5 leukaemia (monocytic sarcoma) is difficult, although features such as abundant cytoplasm and the presence of some reniform nuclei are helpful. If there is no peripheral blood or bone marrow involvement and only fixed paraffin-embedded tissues are available, demonstration of lysozyme by an immunoperoxidase technique may confirm the diagnosis but results are not invariably positive. An early diagnosis of M5 leukaemia has therapeutic implications since the disease evolves through a progressive leukaemia phase and systemic therapy is essential.     

Characterization of a Helicobacter pylori neutrophil-activating protein.

Helicobacter pylori-associated gastritis is mainly an inflammatory cell response. In earlier work we showed that activation of human neutrophils by a cell-free water extract of H. pylori is characterized by increased expression of neutrophil CD11b/CD18 and increased adhesiveness to endothelial cells. The work reported here indicates that the neutrophil-activating factor is a 150,000-molecular-weight protein (150K protein). Neutrophil proadhesive activity copurified with this protein, which is a polymer of identical 15K subunits. Specific antibody, prepared against the purified 15K subunit, neutralized the proadhesive activity of the pure protein and of water extracts obtained from different strains of H. pylori. The gene (napA) for this protein (termed HP-NAP, for H. pylori neutrophil-activating protein) was detected, by PCR amplification, in all of the H. pylori isolates tested; however, there was considerable strain variation in the level of expression of HP-NAP activity in vitro. HP-NAP could play an important role in the gastric inflammatory response to H. pylori infection.     

Virus persists in beta cells of islets of Langerhans and infection is associated with chemical manifestations of diabetes. II. Morphologic observations.

Persistence of lymphocytic choriomeningitis (LCM) virus in the islets of Langerhans was associated with mild hyperglycemia and abnormal glucose tolerance test results. Early histopathologic events consisted of occasional perivascular inflammatory mononuclear cells around both islet and acinar cells. Morphometric studies showed an increase in the size of islets from virus-infected mice. By electron microscopy, LCM virions were found within infected beta cells. Cytolytic injury of beta cells was minimal and did not account for the abnormalities of glucose metabolism. In contrast to the findings in islets, ultrastructural studies of acinar cells revealed LCM virions in abundance, vacuolar degeneration, and intracytoplasmic inclusions. This study extends the previous observation that LCM virus infection may persist in beta cells of the islets of Langerhans without causing structural injury but be associated with abnormalities resembling the chemical and histopathologic features of the early stage of Type II (adult-onset) human diabetes mellitus.     

Marek's disease as a model for the Landry--Guillain--Barré syndrome: latent viral infection in nonneuronal cells accompanied by specific immune responses to peripheral nerve and myelin.

In the chicken, Marek's disease virus (MDV) induces a demyelinating peripheral neuropathy that, early in the course of the disease, is histopathologically indistinguishable from that seen in the Landry--Guillain--Barré syndrome in man. A continuing role for a productive infection in the pathogenesis of this disease is unlikely, since neither MDV nor MDV antigens can be characteristically detected in nerves or spinal ganglia examined at necropsy. The authors investigated the possible role of a latent viral infection by explanting and maintaining in vitro the sciatic nerves and spinal ganglia from diseased birds. In these tissues, viral specific products were induced and detected by immunofluorescence and ultrastructural methods early after explanation in well-isolated Schwann cells, satellite cells, and lymphocytes. Later, virus was detected in fibroblasts, macrophages, and neoplastic lymphoblastoid cells. Neurons and myelinating Schwann cells, in contrast, did not replicate the agent. Specific cell-mediated and humoral immune responses to chicken peripheral nerve and peripheral nerve myelin were demonstrated early in the course of the disease. When considered relative to potential pathogenetic mechanisms, these results suggest that Marek's disease neuropathy is initiated by the establishment of a latent viral infection in neuronal supporting cells. A specific immune response to viral-induced antigens on these cells could, in turn, result in subsequent demyelination.     

A family study of bipolar I disorder in adolescence. Early onset of symptoms linked to increased familial loading and lithium resistance

Lifetime rates of psychiatric illness were compared in relatives of adolescent probands with bipolar I disorder and in relatives of age-matched schizophrenic controls. Familial aggregation of major affective disorders was observed in bipolar probands, the rate of bipolar I disorder greatly exceeding that reported in relatives of adult bipolar probands. Adolescent probands with childhood onset of psychiatric disturbance were distinguished from probands who had no premorbid childhood psychiatric abnormality in two ways: (1) significantly increased aggregation of bipolar I disorder in first-degree relatives; and (2) poorer antimanic response to lithium carbonate. These data underscore important heterogeneity in adolescent-onset bipolar disorder.     

Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Human Brain Tumors

In this study, we investigated the expression patterns of 15 matrix metalloproteinases (MMPs) and three tissue inhibitors of metalloproteinase in gliomas, medulloblastomas, and normal brain tissue. By Northern blot analysis we found increased levels of mRNAs encoding for gelatinase A, gelatinase B, two membrane-type MMPs (mt1- and mt2-MMP), and tissue inhibitors of metalloproteinase-1 in glioblastomas and medulloblastomas. We observed a significant increase of mt1-MMP, gelatinase A, gelatinase B, and tissue inhibitors of metalloproteinase-1 in glioblastomas as compared with low-grade astrocytomas, anaplastic astrocytomas, and normal brain. In medulloblastomas, the expression of mt1-MMP, mt2-MMP, and gelatinase A were also increased, but to a lesser extent than that observed in glioblastomas. These data were confirmed at the protein level by immunostaining analysis. Moreover, substrate gel electrophoresis showed that the activated forms of gelatinases A and B were present in glioblastomas and medulloblastomas. These results suggest that increased expression of mt1-MMP/gelatinase A is closely related to the malignant progression observed in gliomas. Furthermore, the present study demonstrates, to our knowledge for the first time, that medulloblastomas express high levels of MMP.     

A complex translocation in a 5-year-old boy with acute myeloblastic leukemia

A complex translocation [t(2;10;11)(q34;q11;q13)], an extra chromosome #8, and a duplication of 17q were the major findings in blast cells found in the bone marrow of a 5-yr-old boy with AML-M2 both before treatment and during relapse. The child died 8.5 mo after diagnosis, despite intensive combination chemotherapy.     

Changes in Schwann cells and vessels in lead neuropathy.

Transmission electron microscopy (TEM) of peripheral nerve in rats receiving 6% lead carbonate for 4-10 weeks provided evidence of a specific Schwann cell injury, associated with demyelination. Intranuclear inclusions in Schwann cells appeared within 2 weeks of administration of a lead-containing diet. Swelling of Schwann cells and disintegration of their cytoplasm was evident at 4 weeks. Distinctive electron-dense inclusions appeared in both Schwann and endothelial cells during the period of intoxication and were ultrastructurally identical to pathognomonic inclusions of lead poisoning seen in renal tubular epithelial cells. Scanning microscopy (SEM) with electron-probe microanalysis was used to identify the lead-containing deposits. In addition to Schwann cell changes, vessels revealed endothelial cell injury and alteread permeability to macromolecules. Since morphologic changes of Schwann cells precede the development of altered vascular permeability and endoneurial edema, it appears that lead gains access to the endoneurium prior to the development of altered vascular permeability, suggesting that edema and altered endoneurial fluid pressure are epiphenomena that supervene after demyelination occurs. Remyelination, Schwann cell proliferation and formation of onion bulbs are manifestations of persistent toxic injury to myelin-sustaining cells, resulting in chronic demyelination.