PubMed Health⌕ Search

Biomedical subjects

N Hurwitz

Publications and source records attributed to N Hurwitz.

At least 19 recordsLinked to original sources
PubMed2004

Telepathology on the Solomon Islands--two years' experience with a hybrid Web- and email-based telepathology system.

The National Referral Hospital in Honiara, Solomon Islands, has used an Internet-based system in Switzerland for telepathology consultations since September 2001. Due to the limited bandwidth of Internet connections on the Solomon Islands, an email interface was developed that allows users in Honiara to submit cases and receive reports by email. At the other end, consultants can use a more sophisticated Web-based interface that allows discussion of cases among an expert panel. The result is a hybrid email- and Web-based telepathology system. Over two years, 333 consultations were performed, in which 94% of cases could be diagnosed by a remote pathologist. A computer-assisted 'virtual institute' of pathologists was established. This form of organization helped to reduce the median time from submission of the request to a report from 28 h to 8.5 h for a preliminary diagnosis and 13 h for a final report. A final report was possible in 77% of all submitted cases.

Electronic Mail↗
PubMed2001

Alterations on the 5' noncoding region of the BCL-6 gene are not correlated with BCL-6 protein expression in T cell non-Hodgkin lymphomas.

The BCL-6 proto-oncogene is expressed in germinal center B lymphocytes, in their neoplastic counterparts, and in a subpopulation of germinal center and perifollicular T lymphocytes. Rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene have been demonstrated in a large majority of diffuse large B cell lymphomas. Some, but not all, of these genetic alterations lead to dysregulation of the protein. Recently, anaplastic large cell lymphomas with T and null cell phenotypes, as well as T lymphoblastic lymphomas, have also been reported to exhibit immunoreactivity to the anti-BCL-6 antibody. We collected 33 T cell non-Hodgkin lymphomas (T-NHLs) and analyzed their expression of the BCL-6 protein by immunohistochemistry and investigated the organization of the bcl-6 gene by Southern blot and single strand conformation polymorphism (SSCP). The expression of BCL-6 was demonstrated in 37.5% of lymphoblastic (LBL), 40% of anaplastic large cell (ALCL), and 33% of peripheral T cell lymphomas (PTCL). BCL-6-positive malignant cells exhibited the CD4+ or CD4+/CD8+ phenotype. The bcl-6 gene was in a germline configuration in all T-NHLs examined, and a mutation at the first exon-intron boundary region structure of the wild-type bcl-6 gene was detected in 3 of 12 PTCL. One case of PTCL with mutations of the 5' noncoding region expressed BCL-6. In conclusion, expression of the BCL-6 protein is demonstrable independently of bcl-6 alterations in T-NHLs. This further suggests that molecular mechanisms other than rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene can result in expression of the protein. Whether these lymphomas arose from T cells expressing BCL-6 or expressed BCL-6 as part of the malignant transformation process needs to be determined. Finally, structural alterations of bcl-6 are rare in T-NHLs, but mutations do occur in the 5' noncoding region. We suggest that expression of BCL-6 in T cells may facilitate lymphomagenesis by repressing critical cytokines and cell cycle regulators.

Blotting, Southern↗
PubMed2000

Diagnosis and treatment of intravascular lymphomatosis.

OBJECTIVE: To describe a patient with unusually good outcome of a rare, high-grade lymphoma that often involves the nervous system. DESIGN: Case report. SETTING: University hospital. CASE: A 70-year-old pharmacist first presented with meningoencephalitislike symptoms and 6 months later with acute confusional state followed by complex partial status epilepticus. Diagnosis of intravascular lymphomatosis was made using detection and biopsy of a bilateral adrenal tumor. MAIN OUTCOME AND RESULTS: Polychemotherapy consisting of CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) led to complete remission. The patient's survival time currently exceeds 21/2 years. CONCLUSIONS: The possibility of intravascular lymphomatosis should be considered in adult patients with unclear meningoencephalitic syndrome, acute confusional state, dementia, or other unexplained neurologic conditions with signs of a systemic disease. In intravascular lymphomatosis, as in other high-grade non-Hodgkin lymphomas, CHOP polychemotherapy should be the standard treatment.

Aged↗
PubMed2000

Chronic overexpression of membrane-bound flt3 ligand by T lymphocytes in severe aplastic anaemia.

Aplastic anaemia (AA) is an immune-mediated bone marrow failure associated with high serum levels of flt3 ligand (FL). We examined expression of the membrane-bound isoform of FL in peripheral blood and bone marrow cells from AA patients at diagnosis (n = 16) and after immunosuppressive (IS) treatment (n = 36). Flow cytometry demonstrated strongly increased FL levels on the cell surface of T lymphocytes in AA relative to normal controls (P < 0.0001). T-cell-specific expression of membrane-bound FL was confirmed by confocal microscopy. FL mRNA and total cellular FL protein levels were increased about threefold. Overexpression of FL in AA was observed for up to 20 years after IS treatment. FL levels correlated inversely with CD34+ cell numbers and the colony-forming ability of AA bone marrow (R = -0.68 and -0.85 respectively). Histological examination of spleen specimens and bone marrow biopsies gave no evidence of degeneration or fibrosis due to prolonged exposure to high FL. Levels of membrane-bound FL were not increased in autoimmune diseases (n = 23), including rheumatoid arthritis and lupus erythematosus, nor in graft-versus-host disease (n = 8). Chronic overexpression of FL on the surface of T lymphocytes in AA, but not in other T-cell-mediated disorders, suggests that membrane-bound FL plays a role in cell-cell interactions in bone marrow failure and may be important for long-term haemopoietic recovery.

Adolescent↗
PubMed2000

Bone marrow examination for primary diagnosis and follow-up in patients with lymphoproliferative disorders. An overview with emphasize on bone marrow histology.

The aim of his overview is to provide some insight into the manifold applications of bone marrow examination in lymphoproliferative disease. Having a large selection of methods any clinician working in this field should be familiar with the diagnostic relevance of each method for a given diagnostic problem. The choice of the appropriate investigations will warrant a correct diagnosis and helps to lower health expenses. Because of the multiplicity of the methods, often performed at different institutions, a lot of confusion can be caused by conflicting interpretation of isolated results. A diagnosis should never be based on isolated findings such as immunophenotyping or demonstration of a clonal population. Results of various investigations are to be integrated into a final diagnostic concept, which will be the basis for therapeutic decisions.

Biopsy↗
PubMed1996

Immunotactoid-like glomerulopathy with massive fibrillary deposits in liver and bone marrow in monoclonal gammopathy.

At autopsy, massive nonamyloid fibrillar deposits, immunoreactive to IgG and kappa light chain, were found in glomeruli, liver, and bone marrow of a 72-year-old woman. The patient suffered from severe nephrotic syndrome, hepatomegaly and cholestasis, normochromic anemia, and IgG kappa monoclonal gammopathy. Fibrillary glomerulopathies, most often denoted as fibrillary glomerulonephritis or immunotactoid glomerulopathy, are generally considered to have deposits restricted to the glomeruli. However, this study indicates that fibrillary deposits may be a systemic manifestation of fibrillary glomerulonephritis or immunotactoid glomerulopathy, at least when the patient is suffering from a monoclonal gammopathy.

Aged↗
PubMed1996

Fatal vascular leak syndrome with extensive hemorrhage, peripheral neuropathy and reactive erythrophagocytosis: an unusual complication of recombinant IL-3 therapy.

A 39-year-old patient with severe aplastic anemia (AA), resistant to therapy, received recombinant human IL-3 (rhIL-3) on a phase I/II trial. During treatment she developed disseminated skin lesions, suggestive of vasculitis, and severe progressive peripheral neuropathy culminating in complete paralysis. She died 25 days after beginning treatment from profuse bleeding. On autopsy, evidence of vascular leaks with widespread bleeding and extensive hemorrhagic involvement of peripheral nerves was found. An additional feature was massive reactive erythrophagocytosis in lymph nodes, spleen and bone marrow. The coincidence between rhIL-3 administration and the dramatic events suggest a causal relation. As a possible pathogenic mechanism, an rhIL-3 induced excessive stimulation of macrophages and production of secondary cytokines such as tumor necrosis factor (TNF) is suggested. TNF is considered as a major factor in the development of both a vascular leak and reactive erythrophagocytosis. This case report can be regarded as an example of the possible unusual pathologic phenomena we may expect to see in the near future with increasing use of growth factors.

Adult↗
PubMed1995

Differential activation of yeast adenylyl cyclase by Ras1 and Ras2 depends on the conserved N terminus.

Although both Ras1 and Ras2 activate adenylyl cyclase in yeast, a number of differences can be observed regarding their function in the cAMP pathway. To explore the relative contribution of conserved and variable domains in determining these differences, chimeric RAS1-RAS2 or RAS2-RAS1 genes were constructed by swapping the sequences encoding the variable C-terminal domains. These constructs were expressed in a cdc25ts ras1 ras2 strain. Biochemical data show that the difference in efficacy of adenylyl cyclase activation between the two Ras proteins resides in the highly conserved N-terminal domain. This finding is supported by the observation that Ras2 delta, in which the C-terminal domain of Ras2 has been deleted, is a more potent activator of the yeast adenylyl cyclase than Ras1 delta, in which the C-terminal domain of Ras1 has been deleted. These observations suggest that amino acid residues other than the highly conserved residues of the effector domain within the N terminus may determine the efficiency of functional interaction with adenylyl cyclase. Similar levels of intracellular cAMP were found in Ras1, Ras1-Ras2, Ras1 delta, Ras2, and Ras2-Ras1 strains throughout the growth curve. This was found to result from the higher expression of Ras1 and Ras1-Ras2, which compensate for their lower efficacy in activating adenylyl cyclase. These results suggest that the difference between the Ras1 and the Ras2 phenotype is not due to their different efficacy in activating the cAMP pathway and that the divergent C-terminal domains are responsible for these differences, through interaction with other regulatory elements.

Adenylyl Cyclases↗
PubMed1995

Interleukin-12 expression in human lymphomas and nonneoplastic lymphoid disorders.

Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced by lymphocytes and stimulated monocytes. Little is known about the production and possible role of IL-12 in human lymphoproliferative disorders. We examined IL-12 expression by immunohistochemistry using antibodies recognizing the p40, p35 subunits, and the p70 heterodimeric IL-12 protein, and by Northern blot in lymph nodes from patients with Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL), and nonneoplastic lymphoid lesions. In the majority of the HD cases (28 of 34), IL-12 immunoreaction was found in small lymphoid cells cultured around Hodgkin and Reed-Sternberg (H&RS) cells. No IL-12 signal was seen in H&RS cells. Transcripts for IL-12 were found by Northern and dot blot analysis in 13 of 19 (IL-12 p40) and 11 of 19 (IL-12 p35) cases. The HD cases were further examined for the presence of Epstein-Barr virus (EBV) latent membrane protein (LMP-1). All cases with EBV-LMP-1 positivity (22 of 34 cases) also expressed IL-12. No IL-12 immunoreaction was found in neoplastic cells of 33 cases of various NHLs, which were all LMP-1 negative and showed no EBV-genome sequence, as assessed by polymerase chain reaction (PCR). In 24 nonneoplastic lymphoid lesions, few dispersed IL-12 positive cells were seen in the parafollicular area and in the sinus of the lymph node. The marked presence of IL-12 in the majority of HD cases indicates that IL-12 might play a role in the pathobiology of HD, suggesting that this cytokine is involved in EBV-positive HD.

Biomarkers↗
PubMed1995

Complex IgA gammopathy in Gaucher's disease.

A 55-year-old Jewish patient was simultaneously diagnosed as having Gaucher's disease and IgA multiple myeloma. Serum protein electrophoresis and immunoelectrophoresis showed two different IgA kappa type monoclonal spikes. After four years of observation, a rapid fatal course of disease developed together with expression of J chain protein and an additional IgA lambda paraprotein. Although dysproteinaemias and multiple myeloma have occasionally been reported in Gaucher's patients, such a complex gammopathy has to the best of our knowledge not yet been described.

Antigens, CD↗
PubMed1995

A deletion mutant of the LMP1 oncogene of Epstein-Barr virus is associated with evolution of angioimmunoblastic lymphadenopathy into B immunoblastic lymphoma.

The latent membrane protein 1 (LMP1) oncogene is one of the major proteins synthesized by the Epstein-Barr virus (EBV). It is expressed in Reed-Sternberg cells of Hodgkin's disease (HD), tumor cells of nasopharyngeal carcinoma (NPC), and immunoblasts of angioimmunoblastic lymphadenopathy (AILD). A particular LMP1 deletion mutant was recently identified in NPC and clinically and histologically aggressive HD. We studied two patients with AILD that subsequently progressed into immunoblastic lymphoma (IBL) in order to investigate whether the LMP1 deletion mutant was implicated in progression of AILD into IBL. Immunohistology and in situ hybridization were performed on diagnostic biopsies. DNA extracted from fresh frozen material was used for rearrangement studies and polymerase chain reaction (PCR) based amplification and sequencing of portions of the LMP1 gene. Immunohistochemistry revealed B cell origin of both cases of IBL. In the first patient clonal rearrangement of the immunoglobulin heavy-chain gene was present in IBL but not in AILD. In this patient, scattered immunoblasts of AILD and numerous tumor cells of B-IBL were shown to contain EBV transcripts (EBER1) and to express LMP1. Sequence analysis of the LMP1 gene from AILD and IBL in the first, and from IBL in the second patient, revealed identical deletions and point mutations. This LMP1 deletion mutant is identical to those which have been reported in HD and NPC. Its association with evolution of AILD into B-IBL, aggressive HD and NPC, suggests that this particular mutant is more widespread than originally thought and is clinically relevant.

Adult↗
PubMed1994

[gamma-heavy chain production as an epiphenomenon in non-Hodgkin's lymphoma].

A 46-year-old woman was found to have localized lymphoplasmocytic lymphoma (low-malignancy non-Hodgkin lymphoma). Repeated recurrences required various chemotherapy courses with different drugs. Gamma heavy chains in serum and urine, as well as in blast cells in bone marrow, were first found 3 years later as part of a follow-up examination. When the lymphoplasmocytic lymphoma subsequently changed into a highly malignant disseminated large-cell lymphoma, the monoclonal gamma heavy chain-producing components no longer occurred. During continuing treatment and presumably selection of different cell clones the now terminal chemotherapy-resistant lymphoma again produced biclonal IgG heavy chains. The gamma heavy chain production added little to the histomorphological characterization of the underlying lymphoma, as well as its treatment and prognosis.

Combined Modality Therapy↗
PubMed1993

Epstein-Barr virus subtype distribution in angioimmunoblastic lymphadenopathy.

The tissues of 16 patients bearing a T-cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for the distribution of Epstein-Barr virus (EBV) subtypes 1 and 2. EBV-association had been proven in these cases by polymerase chain reaction (PCR) for EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER) and immunohistology for EBV-encoded latent membrane protein (LMP). PCR and EBER-ISH produced mostly identical results, but some cases were positive with only one of the 2 methods employed. LMP was detected in a few large cells of 8/13 cases. Twelve cases were investigated for the distribution of EBV subtypes. One case contained EBV genome of subtype 2, 3 cases contained subtype 1 and 4 cases contained both subtypes. Four cases could not be typed. These findings suggest that in AILD, as in AIDS-associated lymphomas and lymphomas of the lethal midline granuloma type, subtype 2 of EBV may occur, perhaps in relation to an immunodysfunction developing progressively in these patients.

Antigens, Viral↗
PubMed1993

Soft tissue response to textured silicone implants in an animal experiment.

In a study on rats to assess soft tissue response to textured silicone implants, ellipsoid 15 x 20 mm pieces from the bag of a Biocell breast prosthesis were implanted under the dorsal skin. Histological examinations including immunohistochemical detection of myofibroblasts were made 2 weeks and 1, 3, 6, and 8 months after implantation (12 specimens for each time interval). On the smooth side of the implant, which served as a control, the thin connective tissue capsule characteristically seen with silicone elastomer implants developed within a month. Myofibroblasts were present after the first month and appeared to reach a peak 3 months after implantation, after which they showed marked regression. On the textured side of the implant, villous processes were a characteristic feature of the capsules; originating in a common basal layer, they penetrated into the cavities of the implant. Collagen deposits and myofibroblasts only became more evident during the third month after implantation; they were limited to the common basal layer of the capsule, though foreign body reaction persisted in the villous processes until the end of the experiment. The experimental study, limited to an 8-month period after implantation, showed that texturing of the implant surface prevents compact capsule development and considerably delays or inhibits the maturation process.

Animals↗
PubMed1992

Extranodal multilobated B-cell lymphoma: diagnosis by fine needle aspiration.

Malignant lymphoma with multilobated nuclei is a rare variant of follicle centre cell lymphoma. We describe a 34-year-old patient who initially presented with enlarged cervical and inguinal lymph nodes due to a histologically proven centroblastic-centrocytic lymphoma. Two years later, she developed a soft tissue mass in the gluteal area and malignant lymphoma with multilobated nuclei was diagnosed on fine needle aspiration.

Adult↗
PubMed1991

Late appearance of thrombotic thrombocytopenic purpura after autoimmune hemolytic anemia and in the course of chronic autoimmune thrombocytopenic purpura: two case reports.

The association between thrombotic thrombocytopenic purpura (TTP) and autoimmune hematological conditions is reported in 2 patients. In a 35-year-old man, acute autoimmune hemolytic anemia (AIHA) was diagnosed in 1960; until 1965 he was free of disease, when he abruptly developed TTP and failed to respond to blood transfusions and corticosteroids. In a 14-year-old girl, autoimmune thrombocytopenic purpura (AITP) was diagnosed in 1981 and treated with corticosteroids and splenectomy. Four years later the patient was admitted with acute catastrophic signs and symptoms of TTP and failed to respond to plasmapheresis and plasma transfusions. The present case reports of associations between AIHA and AITP with TTP support the connection of the latter with abnormalities of the immune system.

Adolescent↗
PubMed1990

[T-cell lymphoma].

8 patients with lymphoproliferative disorders of T-cell origin were diagnosed during the years 1985-1987. They included 2 cases of so-called Lennert's lymphoma, 1 case of T-cell lymphoma simulating malignant histiocytosis and 1 case of T-cell lymphatic lymphoma with splenic T-cell lymphoma which survived 10 years. The other cases presented with peripheral T-cell lymphomas. Immunologic typing of malignant lymphomas with cell suspensions is of diagnostic value.

Diagnosis, Differential↗