Biomedical subjects
Publications and source records attributed to Z N Berneman.
Two cases of pneumococcal sepsis in splenectomized patients were complicated by purpura fulminans. In addition, acute renal failure developed in both patients, and myolysis in one. Immunological findings in the patient with myolysis suggest a possible role of pneumococcal antigen-containing circulating immune complexes in the pathogenesis of these complications.
With Percoll density gradients, blasts from peripheral blood and bone marrow could be separated with a significant enrichment, and very often with a high degree of purity. This allowed a study of selected cases, where the separated sample exhibited chromosome abnormalities and/or an abnormal DNA content distribution (as measured by DNA-flow cytometry). The anomalies were shown to be associated with the separated blast fraction.
The bone marrow of a patient with pancytopenia showed dyserythropoiesis, dysmegakaryocytopoiesis and 13% blasts. The patient was hypertransfused and the pancytopenia resolved completely for 1 month, while the blastic infiltration in the bone marrow remained. Three months later a frank acute lymphoblastic leukaemia developed.
The case of a 74-year-old female with an IgD kappa plasma cell leukemia is presented. In contrast to the majority of the cases in the literature, this patient responded rather well to melphalan and prednisolone and survived for 20 months after starting treatment. Another remarkable feature was the simultaneous occurrence of a double uterine neoplasm, a malignant mixed Müllerian tumor of the homologous variety (also called carcinosarcoma).
Research towards potential curative transplantation of human embryonic stem (hES) cell-derived grafts in a variety of diseases has become an important topic since the successful derivation and propagation of hES cells from the inner cell mass of a blastocyst. However, clinical applicability can only be established after intensive laboratory studies that should elaborate on two major topics: A) the development of efficient, controlled and stable hES cell differentiation protocols for any specific cell type, and B) the induction of immunological tolerance against transplanted allogeneic hES cell-derived cell types. This review will briefly discuss: A) current possibilities in hES cell differentiation, followed by the development of viral, DNA and mRNA-based gene transfer strategies for hES cells, and B) possible immune modulation strategies for inducing immune tolerance against allogeneic hES cell transplants.
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HHV-7 first isolated in 1990 from a healthy individual, is a ubiquitous agent. The second independent isolation of HHV-7 from a chronic fatigue syndrome patient was reported in 1992. The seroepidemiology of HHV-7 suggested that its prevalence rate in the U.S.A. population is > 85%; however, in Japan a low prevalence rate has been reported. HHV-7 can be more readily isolated from the saliva than HHV-6. The primary infection of HHV-7 appears later in life than HHV-6. No disease has been reported that is etiologically linked to HHV-7. HHV-7 is more closely related to HHV-6 and the human cytomegalovirus than other members of the human herpesvirus family.
The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Kutapressin (KU), a drug that has been available to practicing physicians for over 50 years, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus, under various conditions. Either pretreatment of the cells prior to infection or treatment shortly after infection, inhibited viral replication by > 90%. Indirect evidence suggests that KU may inhibit viral attachment to cellular receptors, and inhibit intracellular maturation of the virus. Given these in vitro findings, and the low frequency of toxicity reported with the use of KU, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted.
The recently discovered human herpesvirus-6 (HHV-6) is being associated with an increasing number of conditions in which there is evidence of immunologic dysfunction. A number of widely available antiviral agents have shown little or no activity against the virus. We found that Ampligen [Poly (1): Poly (C12U), a synthetic, mismatched, double-stranded RNA, has potent, previously unexpected antiviral effects. Cells known to allow replication of HHV-6 were infected with the virus and treated with Ampligen under various conditions. When cells were pretreated with Ampligen (concentrations of 100 or 200 micrograms/ml) prior to infection or treated shortly after infection, viral replication was inhibited by 46-98%. At 100 and 200 micrograms/ml, Ampligen also inhibited the DNA polymerase activity of HHV-6 by 42-98%. When lower concentrations of Ampligen (10 and 50 micrograms/ml) were used, only pretreatment of cells, with Ampligen, followed by virus infection and carrying the infected cells with Ampligen, significantly inhibited HHV-6 infection (83.7 and 89.1% respectively). Indirect evidence suggests that Ampligen may inhibit viral attachment to cellular receptors and/or inhibit intracellular maturation of the virus. The above concentrations of Ampligen were not toxic to the cells used in the study. Given these in vitro findings, and the low frequency of toxicity reported with the use of Ampligen, clinical trials of this drug in patients with evidence of reactivated HHV-6 infection would seem to be warranted.