Molecular analysis of the retinoblastoma (RB1) gene in acute myeloid leukemia patients

Patient 1: A 48-year-old man was admitted to Osaka Red Cross Hospital because of fever and dyspnea. Laboratory examination revealed pancytopenia, liver dysfunction and hematostatic abnormality. Chest radiographs obtained on admission revealed ground-glass opacity in both lung fields, and an analysis of arterial blood showed severe hypoxemia (PaO2:46.8 Torr). Pulse therapy with methylprednisolone was started. Although the hypoxemia subsided and radiographic findings rapidly improved, pancytopenia persisted. Examination of bone marrow aspirate revealed mature histiocytes with marked hemophagocytosis. Amplified Mycobacterium tuberculosis direct tests of bronchoalveolar lavage fluid, sputum, urine, and bone marrow were all positive, and Mycobacterium tuberculosis was cultured from sputum and urine. Although the patient was taking antituberculous agents, his pancytopenia persosted. Treatment with etoposide induced remssion. Patient 2: A 19-year-old woman was admitted to Osaka Red Cross Hospital because of prolonged cough and fever. Laboratory examination revealed leukocytosis, liver dysfunction, and hematostatic abnormality. Serologic tests provided conclusive evidence of Mycoplasma infection and a CRP test was strongly positive. Chest radiographs obtained on admission revealed infiltration shadows in the middle and lower lung fields on both sides, with left pleural effusion. An analysis of arterial blood showed hypoxemia (PaO2: 54.2 Torr). Examination of bone marrow and pleural effusion samples revealed mature histiocytes with marked hemophagocytosis. Although treatment with antibiotics and pulse therapy with methylprednisolone was started, the patients respiratory functions deteriorated. Endotracheal intubation was performed. Therapy with etoposide induced remission. Hemophagocytic syndrome associated with Mycoplasma infection and tuberculosis appears to be exceedingly rare. In these 2 cases, it was difficult to achieve remission with therapy for the underlying infections, but etoposide treatment was effective.     

Ex vivo generation of functional dendritic cells from mobilized CD34+ hematopoietic stem cells

Gene engineering to enhance tumour immunogenicity and elicit curative responses against established tumours and tumour recurrences has become an attractive prospect. Gene engineering enables new genes to be selectively inserted into the genome of a tumour cell, or the construction of new fusion plasmids coding tumour antigens and immunomodulatory molecules. The rationale behind current research is to enhance the immune recognition of tumour antigens through their association with the molecules on which immune recognition depends. The immunotherapy data obtained in many experimental tumour systems provide a realistic assessment of the potential and limits of this technological approach. Experimental vaccination of rodents has been shown to induce a significant immune memory, even against poorly immunogenic tumours, that can prevent tumour growth and cure initial metastases, but is poorly effective against established tumours. Its use in tumour prevention is a fresh dawning perspective.     

Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents

Vinylidenebisphosphonic acid tetraethyl ester (1) and diazo ketones 7a-1 in ether at 22 degrees C yield pyrazoline bisphosphonate tetraethyl esters 8a-1 in moderate to good yield. These compounds were evaluated in animal models of arthritis: rat adjuvant-induced polyarthritis (AIP) and murine antigen-induced arthritis (AIA) and a murine model of chronic inflammation, the delayed type hypersensitivity granuloma reaction (DTH-GRA). (5-Benzoyl-2,4-dihydro-3H-pyrazol-3-ylidene)-bisphosphonic acid tetraethyl ester (8a), and [5-(3-fluorobenzoyl)-2,4-dihydro-3H-pyraxol-3-ylidene]- bisphosphonic acid tetraethyl ester (8d) significantly inhibited the arthritis models, AIP (15 mg/kg) and AIA (25 mg/kg), as well as the DTH-GRA (25 mg/kg). Conversion of 8a to the corresponding bisphosphonic acid, 10a, resulted in loss of activity. Compounds with alkyl substituents on the pyrazoline nitrogen, 9a-d, were inactive in the DTH-GRA. These results show that 8a and 8d have novel antiinflammatory activity and are capable of inhibiting chronic arthritis and inflammation in animals. Such compounds might be useful in man for treating chronic tissue injury associated with arthropathies such as inflammatory joint disease as well as other chronic inflammatory diseases.     

The modulation of cellular responses to poly(2-hydroxyethyl methacrylate) hydrogel surfaces: phosphorylation decreases macrophage collagenase production in vitro

We examined the regulation of collagenase production by the monocyte/macrophage THP-1 cell line when these cells were exposed to poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel surfaces with different chemistries and morphologies. Tissue culture modified polystyrene (TCP), used as a control surface, induced the maximum collagenase response. Copolymer hydrogels containing 2-ethoxyethyl methacrylate (EMA) or methyl methacrylate (MMA) also induced a high response, while PHEMA hydrogels induced a low level response and the phosphorylated hydrogel induced no response. This pattern was altered when the morphology of the hydrogels was changed to that of a sponge. The overall enzyme response to the sponge hydrogels was lower than that to the homogeneous hydrogels. Sponges containing EMA and MMA produced low level response relative to the TCP control. PHEMA and phosphorylated sponges produced little and no response respectively. The dramatically reduced enzyme response to phosphorylated surfaces was not a consequence of cell death, and may be a phenomenon related to changes in cell surface charge.     

Post-breakdown bulk oscillations in gold-doped silicon p+−i−n+ double-injection diodes

Experimental work on post-breakdown bulk oscillations in n-type gold-doped phosphorus-compensated p⁺?i?n⁺ double-injection diodes is presented. An empirical relationship for the frequency of oscillation in this region is derived for the first time and discussed.