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Braz J Med Biol Res. 2001 Feb;34(2):221-6.
Myosin V and iNOS expression is enhanced in J774 murine macrophages treated with IFN-gamma.

Reis D, Souza M, Mineo J, Espindola F.

Departamento de Imunologia, Microbiologia e Parasitologia, Universidade Federal de Uberlandia, Brasil.

Actin-based motor protein requirements and nitric oxide (NO) production are important features of macrophage activity during phagocytosis or microbicidal processes. Different classes of myosins contribute directly or indirectly to phagocytosis by providing mechanical force for phagosome closure or organelle movement. Recent data have shown the presence of myosins IC, II, V and IXb in phagosomes of bone marrow-derived murine macrophages. In our investigation we demonstrated the presence of different classes of myosins in J774 macrophages. We also analyzed the effect of gamma interferon (IFN-gamma), with or without calcium ionophore or cytochalasin B, on myosins as well as on inducible nitric oxide synthase (iNOS) expression and NO production. Myosins IC, II, Va, VI and IXb were identified in J774 macrophages. There was an increase of myosin V expression in IFN-gamma-treated cells. iNOS expression was increased by IFN-gamma treatment, while calcium ionophore and cytochalasin B had a negative influence on both myosin and iNOS expression, which was decreased. The increases in NO synthesis were reflected by increased iNOS expression. Macrophages activated by IFN-gamma released significant amounts of NO when compared to control groups. In contrast, NO production by calcium ionophore- and cytochalasin B-treated cells was similar to that of control cells. These results suggest that IFN-gamma is involved in macrophage activation by stimulating protein production to permit both phagocytosis and microbicidal activity.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11175497&dopt=Abstract

Nat Cell Biol. 2001 Feb;3(2):150-7.
RANTES promotes growth and survival of human first-trimester forebrain astrocytes.

Bakhiet M, Tjernlund A, Mousa A, Gad A, Stromblad S, Kuziel WA, Seiger A, Andersson J.

Karolinska Institutet, Department of Medicine, Centre for Infectious Medicine, Huddinge University Hospital, SE-141 86 Stockholm, Sweden.

We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferon-gamma (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11175747&dopt=Abstract

Nat Immunol. 2001 Feb;2(2):157-64.
IL-18-stimulated GADD45 beta required in cytokine-induced, but not TCR-induced, IFN-gamma production.

Yang J, Zhu H, Murphy TL, Ouyang W, Murphy KM.

Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA.

Interleukin-12 (IL-12) and IL-18 induce synergistic transcription of interferon gamma (IFN-gamma) that is T cell receptor (TCR)-independent, not inhibited by cyclosporin A and requires new protein synthesis. To characterize this pathway, we screened for genes that are induced in IL-12- and IL-18-treated T helper type 1 cells. GADD45 beta, which activates mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase kinase 4 (MEKK4), was induced by IL-18 and augmented by IL-12. GADD45 beta expression in naive CD4+ T cells activated p38 MAPK and selectively increased cytokine-induced, but not TCR-induced, IFN-gamma production. Kinase-inactive MEKK4 and inhibition of the p38 MAPK pathway both selectively inhibit cytokine-induced, but not TCR-induced, IFN-gamma production. Thus, the synergy between IL-12 and IL-18 may involve GADD45 beta induction, which can maintain the MEKK4 and p38 MAPK activation that is necessary for cytokine-induced, but not TCR-induced, IFN-gamma production.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11175814&dopt=Abstract

Am J Surg Pathol. 2001 Feb;25(2):185-96.
Giant cell angioblastoma: three additional occurrences of a distinct pathologic entity.

Vargas SO, Perez-Atayde AR, Gonzalez-Crussi F, Kozakewich HP.

Department of Pathology, Children's Hospital, Boston, Massachusetts 02115, USA.

Giant cell angioblastoma was described previously in a single case report as a congenital soft-tissue tumor with a unique morphology. In the current report, we describe three cases of giant cell angioblastoma found in three infants; one case was congenital and located in the hand, one appeared neonatally in the palate, and one on the scalp of an infant. Clinical findings and results of light microscopy, immunohistochemistry, and electron microscopy were evaluated. All tumors were ulcerated; the hand and palate tumors also infiltrated soft tissue and bone. They exhibited a solid, nodular, and plexiform proliferation of oval-to-spindle cells with a frequent striking, concentric aggregation around small vascular channels. These cells had characteristics of undifferentiated mesenchymal cells, fibroblasts, myofibroblasts, and pericytes. Co-mingled with these cells were large mononuclear and multinucleate giant cells with histiocytic features. The palatal giant cell angioblastoma, excised with positive margins, was managed with interferon-alpha and showed no progression after nearly 5 years. The hand tumor diminished in size after management with interferon-alpha, was subtotally excised, and did not progress after 27 months. Follow-up data are unavailable for the patient with the scalp lesion. Our findings validate the classification of giant cell angioblastoma as a distinct and rare entity that is locally infiltrative but slow growing. The morphology and diverse cellular differentiation are consistent with an unusual form of neoplastic angiogenesis.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11176067&dopt=Abstract

Ann Surg. 2001 Feb;233(2):236-41.
Preoperative systemic chemoimmunotherapy and sequential resection for unresectable hepatocellular carcinoma.

Lau WY, Leung TW, Lai BS, Liew CT, Ho SK, Yu SC, Tang AM.

Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. josephlauhk.edu.hk

OBJECTIVE: To examine the surgical and pathologic findings of 15 patients who had initially unresectable hepatocellular carcinoma (HCC) and received preoperative systemic chemoimmunotherapy and sequential resection. SUMMARY BACKGROUND DATA: More than 80% of patients with HCC present for treatment at an unresectable stage. Conventional treatment has produced a low tumor response rate in this group of patients. Recently, new systemic chemoimmunotherapy has been found to be effective and able to make previously unresectable HCC resectable. Sequential resection after response to chemoimmunotherapy could therefore induce complete clinical remission. METHODS: From July 1996 to February 1999, 150 patients with unresectable HCC were treated with systemic chemoimmunotherapy consisting of cisplatin, alpha-interferon, doxorubicin, and 5-fluorouracil for a maximum of six cycles. The residual tumors were reassessed for resectability after treatment aiming at complete remission in the patients after combined modality treatment. Twenty-seven patients had a more than 50% regression in tumor size (2 complete remissions, 25 partial remissions). Fifteen patients had resectable disease after treatment, and all underwent sequential resection with curative intent. Treatment outcome and the surgical and pathologic features of these 15 patients were studied. RESULTS: Fifteen of 150 patients responded to chemoimmunotherapy and underwent sequential resection. They were considered to have unresectable disease as a result of extensive local disease (with and without major vascular involvement) in 10 patients and the presence of extrahepatic or metastatic disease in 5 patients. All patients except two were hepatitis B carriers. Surgical resection of the residual lesion after chemoimmunotherapy was successful for all patients. Eight of the patients had complete pathologic remission. The rest had minimal residual disease (<5%) only. All 15 patients entered complete clinical remission after surgery. Thirteen patients were still alive as of this writing and two had died of recurrent disease. The 1-, 2-, and 3-year survival rates were 100%, 100%, and 53%, respectively. The mean follow-up period was 27 months (range 15-37). Neither the median disease-free nor overall survival had been reached. Ten patients remained in complete remission as of this writing. CONCLUSION: Combined modalities with systemic chemoimmunotherapy and surgical resection can achieve complete clinical remission and long-term control of disease in patients with unresectable HCC.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11176130&dopt=Abstract

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