Progressive HHV-8-positive classic Kaposi's sarcoma: rapid response to interferon alpha-2a but persistence of HHV-8 DNA sequences in lesional skin.

The pathogenesis of Kaposi's sarcoma (KS) is often attributed to an infectious agent. In particular, the human herpesvirus 8 (HHV-8) was currently shown to be closely related to all known KS types, including HIV-associated KS, European classic KS, African endemic KS and iatrogenic KS. We report here on an HIV-negative, German patient of neither Jewish nor Mediterranean descent with disseminated classic KS showing unusual rapid progression into the tumour stage. After systemic administration of interferon alpha-2a over 4 weeks all tumour lesions cleared completely. Interestingly, HHV-8 DNA sequences detected by nested polymerase chain reaction in KS lesions before the onset of treatment were still present in lesional skin after complete remission of the tumour. No recurrence was seen after a follow-up period of 6 months.

Kaposi's sarcoma: a reevaluation.

Kaposi's sarcoma (KS) is a multicentric neoplasia of microvascular origin arising during development of immunodeficiency in human immunodeficiency virus (HIV)-infected individuals. More than 130 patients with HIV-associated KS (98% male homosexuals; median age, 35 years) have been diagnosed at the Department of Dermatology, University Medical Center Steglitz, Berlin, during the years 1982-1992. Mucocutaneous and visceral involvement was a common finding in patients with HIV-associated KS, increasing from 39% at the first visit to 65% at the last observation. In 90% of the patients significant immunosuppression was found (75% had a CD4+ count < 200/mm3) at the time of first diagnosis. However, immunosuppression was not a prerequisite for the development of KS, since the tumor had been diagnosed before severe immunosuppression was present in about 10% of the patients. Significant prognostic predictors for the final outcome were: (a) the degree of immunosuppression, (b) the presence of mucosal and visceral manifestation, and (c) the past history of opportunistic infections. The median survival time was 28 months in KS patients with more than 300 CD4+ lymphocytes (n = 18), but only 14 months in immunosuppressed (less than 300 CD4+ lymphocytes) individuals with KS (n = 70). The median survival time in the entire group evaluated (n = 89 patients) was 17 months after first diagnosis. In 71 HIV-infected individuals who died at the Berlin Department during the last 8 years, disseminated KS was the major direct or indirect cause of death (49% of cases). Therapeutic benefit for KS patients was observed after long-term administration of recombinant interferon alpha (rIFN-alpha; 9-18 million IU s.c. every 2 days) alone or combined with antiretroviral drugs such as zidovudine over several months. Prolongation of survival was found after such treatment modalities in 30%-40% of treated patients. Bleomycin and vincristine and other systemically used cytostatics have also been applied with moderate results. The etiology of HIV-associated KS is still unknown and coinfection with herpes simplex virus (HSV), cytomegalovirus (CMV), or human papillomavirus (HPV) as well as certain growth-stimulating cytokines (transforming growth factors, TGF; tumor necrosis factor alpha, TNF-alpha; interleukin-6, IL-6; tat; vascular endothelial growth factors, VEGF; oncostatin M) produced by HIV-infected cells may be cofactors. Overall, KS was found to be a tumor with high malignant potential, and the median survival times were short.(ABSTRACT TRUNCATED AT 400 WORDS)

Processing of pseudorabies virus glycoprotein gII.

The glycoprotein complex gII of pseudorabies virus was isolated by immunoprecipitation with the monoclonal antibody M5, which was covalently linked to protein A-Sepharose. After sodium dodecyl sulfate-polyarylamide gel electrophoresis under reducing conditions and blotting onto poly(vinylidene difluoride) membrane, its subunits, gIIa, gIIb, and gIIc, were subjected to N-terminal sequencing. gIIa and gIIb start at position 59 and gIIc starts at position 503 according to the amino acid sequence deduced from the gene, indicating that there is one major protein (gIIa) which is cleaved into the two protein fragments gIIb and gIIc. Protein labeling with 14C-amino acids gave no indication that the three proteins (gIIa, gIIb, and gIIc) of the complex are present in equimolar ratios. It seems that gIIa is only a minor component of the complex, whereas gIIb and gIIc are contained in equimolar amounts.

Bacteriorhodopsin precursor is processed in two steps.

Besides the Coomassie-blue-stained band corresponding to mature bacterioopsin two additional bands of slightly higher apparent molecular masses were observed in purple membrane preparations from Halobacterium halobium by SDS-PAGE. The staining intensity within the triple band pattern varied with the age of the cell culture. For cells in the stationary growth phase the lower band, corresponding to mature bacterioopsin, is the predominant one. Immunodetection and site-specific proteolysis with papain identified the upper band as originating from the previously described precursor of bacterioopsin with its 13-amino-acid-long N-terminal presequence. Our results suggest that the intermediate band is due to a modified precursor of bacterioopsin with a truncated presequence of about eight amino acids. A two-step mechanism for the processing of pre-bacterioopsin to the mature protein in this archaebacterium is proposed.