Isolation of a multinucleated giant cell-forming and hemagglutinin-negative variant of variola virus. Brief report.
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Inoculation of rabbits with permanent B-cell line cultures obtained from Stumptailed Macaques M. arctoides (MAL) which contain lymphotropic herpesvirus and C-type particles has led to the development of generalized lymphomas. The lymphoma cells had rabbit karyotype and did not contain surface an cytoplasmic immunoglobulins. Permanent suspension of lymphoid cell line independent of growth factors was obtained from rabbit lymphoma. The serum of a rabbit with lymphoma transmitted from another rabbit with MAL-induced lymphoma did not react with virus-negative human Raji cells when tested in immunofluorescence. But this serum reacted positively with cytoplasmic antigens of simian 594S-F9 cells (producing lymphotropic herpesvirus and two types of retroviruses, namely, endogenous C-type and HTLV-I-like) and human C91-PL cells (producing HTLV-I). The results obtained demonstrated high oncogenicity of the viruses produced by simian permanent cellular MAL lines for rabbits.
Currently, the immunohistochemical evaluation of cytotoxic granule-associated proteins such as TIA-1 and granzyme B can be carried out on paraffin sections. This procedure has broadened our knowledge of cytotoxic lymphoid neoplasms. Their detection is now regarded as a useful adjunctive in some characterizations of cytotoxic T- or natural killer (NK)-cell lymphoma, mostly in lymphoma of extranodal origin. We report two cases of nodal cytotoxic large T-cell lymphoma with identical biologic properties. Both cases presented with systemic lymphadenopathy, lymphomatous bone marrow involvement, and thrombocytopenia. The clinical course was fulminant, and both patients died within 1 week of presentation. The cells had a characteristic immunophenotype of CD2+, CD3+, CD4-, CD5-, CD8+, CD30 -/+, CD56-, CD57-, TCR alpha/beta+, and TCR gamma/delta-. They also expressed the cytotoxic granule-associated proteins of TIA-1 and granzyme B, and exhibited clonal rearrangements of the T-cell receptor beta chain gene. Monoclonal integration of Epstein-Barr virus was also detected. The present cases exhibited clinicopathological features that were distinct from other types of malignant lymphoma expressing cytotoxic granule-associated proteins.
Being key regulator of oxygen homeostasis hypoxia-inducible factor 1 (HIF-1) plays significant roles in cancer progression as well as in cardiovascular diseases. The modulation of HIF-1alpha activity in vivo may represent a valuable therapeutic approach to these disorders. In order to monitor HIF-1 transcriptional activity, we have developed HIF-1alpha-responsive reporter constructs, in which lacZ gene expression is driven by minimal Hsp70 gene promoter or minimal immediate early promoter of cytomegalovirus (CMV) and a combination of hypoxia response elements from regulatory regions of PGK1, ENO1 and LDHA genes. For the efficient delivery to a wide variety of cell types we chose retroviral and lentiviral vectors as carriers of the reporter cassette. We demonstrate that the obtained reporter system i) has a high inducibility in response to treatments leading to HIF-1alpha activation, ii) shows upregulation in response to HIF-1 activation and downregulation following inhibition of HIF-1alpha expression by small interfering RNA, iii) follows the dynamics of endogenous HIF-1 target gene expression. The retrovirus- and lentivirus-based reporters can be used for high-throughput screening of HIF-1alpha modulators and for the study of crosstalk between HIF-1 and different related signal transduction pathways. Potential applications for the reporters are discussed.
We treated two children with influenza-associated acute encephalopathy by a combination of mild hypothermia and steroid pulse therapy. Case 1, a 2-year-and-3-month-old boy, admitted to our hospital 7 days after the onset of central nervous symptoms. The brain MRI-CT revealed laminar cortical necrosis and severe brain edema. EEG showed very low voltage. Brain edema improved by the combination therapy. He had sequelae, but was able to eat. Case 2, a 1-year-and-10-month-old boy, admitted to our hospital 5 days after the onset of central nervous symptoms. Brain MRI showed frontal dominant cortical edema. EEG showed high voltage delta bursts. The combination therapy was effective, but he remained mental handicapped. The outcome was better compared to our previous cases of acute encephalopathy. The combination therapy is intended to counteract cytokines, and was considered to be an effective treatment against acute encephalopathy associated with an influenza virus infection.
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Central nervous system findings in 30 fatal cases of human immune deficiency viral (HIV) infection are described. Twenty seven patients had acquired immune deficiency syndrome (AIDS) and three patients had serological evidence of HIV infection only (HIV seropositive). Twenty nine patients had neuropathologic abnormalities at autopsy and frequently had more than one neuropathologic process. Neurologic disease was the dominant clinical feature in nineteen patients. The spectrum of neuropathologic disease is similar to that described in other series encompassing direct HIV infection of brain; indirect CNS involvement by opportunistic pathogens differing slightly from other series in their relative frequency; lymphoma and neurovascular disease. This, the first report which serves to document the level of neurologic disease in Irish patients with AIDS and HIV infection should help to provide meaningful information for use in the planning of neurologic and rehabilitation services for these patients.
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Isolated intact influenza virus neuraminidase (NA) molecules of the N9 subtype have been found to possess hemagglutinin (HA) activity which, at equivalent protein concentration, was fourfold higher than that of isolated hemagglutinin molecules of the H3 subtype. The amino-terminal sequence of the N9 NA is the same as in neuraminidases of the eight other influenza A virus NA subtypes previously reported. Viruses possessing N9 NA therefore have two different HA activities and antibody to either HA or NA alone was incapable of inhibiting hemagglutination by the virus. However, antibody to the HA of an H1N9 virus neutralized its infectivity as effectively as it neutralized H1N1 or H1N2 viruses whose neuraminidases have no HA activity. (Antibodies to N9 NA did not neutralize the infectivity of viruses with N9 neuraminidase). 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid inhibited N9 NA activity but had no effect on the HA activity of the isolated N9 NA. One interpretation of this result would be that the HA and NA activities are located in separate sites. Pronase-released N9 NA heads form crystals suitable for X-ray diffraction studies and preliminary data to 2.9 A establish the space group as cubic, I432 with cell dimension a = 184 A. Data extend to beyond 1.9 A resolution, and these will be collected in the future.
Four patients with HIV infection and psychosis from various etiologies, refractory to standard treatments, and suffering from severe extrapyramidal symptoms (EPS), had a marked beneficial response to molindone. There was significant control of neuropsychiatric dysfunction without major adverse side effects. The results suggest that further evaluation is warranted of the use of molindone in treating severely ill, psychotic, or delirious HIV-infected patients.
BACKGROUND: : HIV is associated with a decrease in cellular immunity which allows for persistence of high-risk HPV types and this can predispose the woman to dysplasia or cancer of the gynecologic tract. CASE: : We present a case of Stage 3 vulvar cancer in a 33-year-old HIV positive woman. The patient was treated with primary radiation; unfortunately there was persistent disease. Exenterative surgery was planned but abandoned due to a positive presacral node. CONCLUSION: : The optimal treatment of advanced vulvar cancer in HIV positive patients remains unclear given the small number of cases reported in the literature. Lessons from the anal cancer literature may help inform the care of vulvar cancer patients given the comparable high prevalence of this disease in the patients infected with HIV.
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We describe here the epidemiological and clinical characteristics of 10 HIV-infected patients with paracoccidioidomycosis. All patients were adult males from small towns in Brazil and had a previous history of work or residence in a rural area. The two infections were diagnosed concomitantly in six of the ten patients, and for six of the patients, the mycosis was the first clinical manifestation of HIV infection. Risk factors for HIV infection were injection drug use in some patients and multiple sexual partners in others. Six patients died and autopsy revealed severe disseminated paracoccidioidomycosis in three. Exuberant and severe clinical pictures suggest an alteration in the natural history of this mycosis as a result of HIV immunosuppression. The frequency of paracoccidioidomycosis in the HIV-infected population is not known to differ from that reported for this mycosis in non-HIV patients.
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