Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.     

Multiple gene duplication and expression of mouse bcl-2-related genes, A1

Atrial reentrant tachycardia (ART) was ablated in an anatomically guided approach. Five patients with ART underwent 2 linear incisions without careful pace or activation mapping. One line was from an atrial activation site earlier than P wave onset to the nearest fixed anatomic conduction barrier, i.e., the inferior vena cava or coronary sinus ostium. The other line was made just above or closely crossed the first line vertically. Mean application time was 29 +/- 19 minutes, and the application energy was 14,001 +/- 12,322 joules. Mean follow-up after ablation was 15 +/- 10 months. Three patients underwent electrophysiologic study three months after and sustained ART was not induced. All patients were free of sustained tachycardia events without antiarrhythmic drugs during the postoperative clinical course. Although anatomically guided ablation for ART requires much time and energy, it is easily and effectively done without careful activation or pace mapping, and is indicated if ablation using activation mapping or entrainment technique fails to cure the ART.     

A new triple stain for Helicobacter pylori suitable for the autostainer: carbol fuchsin/Alcian blue/hematoxylin-eosin

OBJECTIVE: To develop an inexpensive stain to simultaneously visualize gastric morphology and Helicobacter pylori. METHODS: Gastric biopsies were stained with Genta stain using manual methods, and with carbol fuchsin/Alcian blue/hematoxylin-eosin using an automatic slide stainer (Sakura DRS-601). Slides were then coded and interpreted by 2 pathologists. Helicobacter pylori was scored using a visual scale (0 [none] to 5 [maximum]). RESULTS: One hundred slides were scored; H pylori was present in 64%. Carbol fuchsin/Alcian blue/hematoxylin-eosin stain gave excellent demonstration of gastric morphology. All positive cases (score > or =2) were correctly interpreted. Thirty-six slides had a score of 1 (< or =2 bacteria per entire slide). Of these, 10 were scored negative by Genta stain and 12 were scored negative by the carbol fuchsin/Alcian blue/hematoxylin-eosin stain (P = not significant). Hematoxylin-eosin was significantly less accurate than either of the other 2 stains (P < .02). CONCLUSION: The carbol fuchsin/Alcian blue/hematoxylin-eosin (El-Zimaity) stain is an economical stain suitable for simultaneous visualization of H pylori infection and gastric morphology.     

Long-term follow-up results of alpha-interferon-based regimens in patients with late chronic phase chronic myelogenous leukemia

The aim of this analysis was to evaluate the efficacy of alpha-interferon (alpha-IFN) regimens in late chronic phase (diagnosis >12 months) chronic myelogenous leukemia (CP-CML). Long-term follow-up results were evaluated in 137 patients with Philadelphia chromosome (Ph)-positive late CP-CML. The alpha-IFN programs were sequential studies with human leukocyte alpha-IFN (seven patients), recombinant alpha-IFN alone (15 patients) or with IFN-gamma (29 patients), hydroxyurea (HU) (19 patients), or low-dose cytarabine (Ara-C) (67 patients). Overall, 57% of the patients achieved complete hematological response (CHR), and 7% obtained partial hematological response. Nineteen patients (15% of the 123 evaluable patients) had a cytogenetic response which was major (Ph-positive <35%) in 10 patients (8%). A trend for better responses was observed with shorter disease duration. The median overall survival from start of therapy was 49 months, with an estimated 5-year survival rate of 41%. Some common pretreatment prognostic factors associated with response did not show statistical associations when applied in late CP-CML; however, characteristics such as smaller spleen size, and lower percentages of peripheral blood and marrow blasts and basophils were associated with better survival experience. When patients were subgrouped according to risk, no significant differences in the incidence of cytogenetic response and in survival outcomes were observed among various risk groups. This study confirms that alpha-IFN-based regimens have a modest activity in late CP-CML, and supports the need to develop investigational strategies aimed at improving patient prognosis in this phase.     

Percutaneous treatment of bronchial artery aneurysm with use of transcatheter coil embolization and thoracic aortic stent-graft placement

Lactic acidosis due to thiamine deficiency is known to complicate chemotherapy and radiotherapy treatment of malignant extracranial tumors, but to the authors' knowledge, this complication has not been reported in patients treated for malignant brain tumors. They report three such cases, demonstrating that this complication can occur during treatment of brain tumors. In all patients, consciousness levels deteriorated within 1 to 2 days. Serum lactic acid levels increased to concentrations between 62 and 96.7 mg/dl, resulting in severe metabolic acidosis. A low blood thiamine level (9 ng/ml) was demonstrated at the onset in one case, and high-dose thiamine infusions dramatically improved lactic acidemia as well as impairment of consciousness in two cases. In the other case, hydrocephalus was suspected initially, resulting in a delay in thiamine supplementation. Clinical differentiation of this form of lactic acidosis from hydrocephalus or tumor progression can be very difficult in a patient undergoing treatment for a malignant brain tumor. Demand for thiamine is thought to be increased in patients with malignant brain tumors, and supplemental thiamine during treatment is necessary to prevent lactic acidosis. When this complication occurs, immediate treatment with sufficient thiamine is essential, together with normalization of pH by using sodium bicarbonate. With timely intervention, the level of consciousness can recover to the preacidotic state with no new neurological deficits.     

Molecular and biologic characterization of a newly established Philadelphia-positive acute lymphoblastic leukemia cell line (Z-33) with an autocrine response to GM-CSF

We have recently established a new Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) cell line, designated Z-33. This line has L2 morphology, ultrastructural characteristics of lymphoblasts and typical B lineage surface markers identical to those observed in the Ph1-positive ALL patient from whom the line was derived. In addition, a rearranged immunoglobulin heavy-chain gene (JH) band was found in Z-33 cells by Southern blot analysis, confirming B cell clonality. Cytogenetic analysis of the cell line revealed t(9;22)(q34;q11.2). Polymerase chain reaction (PCR)-amplified cDNA from Z-33 cells demonstrated an e1-az BCR-ABL junction, and the p190BCR-ABL protein was detected in them by the immune complex kinase assay. Z-33 cells produce interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta, Neither IL-1 beta, G-CSF, TNF-alpha, nor their corresponding antibodies affected the cell line's growth. In contrast, anti-GM-CSF neutralizing antibodies suppressed Z-33 colony formation, and GM-CSF stimulated it in a dose-dependent fashion. In addition, receptor studies with biotinylated GM-CSF demonstrated specific binding to Z-33 cells, indicating that the cells express GM-CSF receptors. Taken together, our data suggest that the Ph1-positive Z-33 ALL cells produce GM-CSF, express GM-CSF receptors, and show an autocrine proliferative response to this cytokine.     

gp25L/emp24/p24 protein family members of the cis-Golgi network bind both COP I and II coatomer

Abstract. Five mammalian members of the gp25L/ emp24/p24 family have been identified as major constituents of the cis-Golgi network of rat liver and HeLa cells. Two of these were also found in membranes of higher density (corresponding to the ER), and this correlated with their ability to bind COP I in vitro. This binding was mediated by a K(X)KXX-like retrieval motif present in the cytoplasmic domain of these two members. A second motif, double phenylalanine (FF), present in the cytoplasmic domain of all five members, was shown to participate in the binding of Sec23 (COP II). This motif is part of a larger one, similar to the F/YXXXXF/Y strong endocytosis and putative AP2 binding motif. In vivo mutational analysis confirmed the roles of both motifs so that when COP I binding was expected to be impaired, cell surface expression was observed, whereas mutation of the Sec23 binding motif resulted in a redistribution to the ER. Surprisingly, upon expression of mutated members, steady-state distribution of unmutated ones shifted as well, presumably as a consequence of their observed oligomeric properties.